Estimation and Stress Study of a Potent Anticoagulant Drug Rivaroxaban by a Validated HPLC Method
|
|
- Corey Logan
- 8 years ago
- Views:
Transcription
1 2 ESTIMATION AND STRESS STUDY OF A POTENT ANTICOAGULANT DRUG RIVAROXABAN BY A VALIDATED HPLC METHOD II Estimation and Stress Study of a Potent Anticoagulant Drug Rivaroxaban by a Validated HPLC Method 21
2 2.1 INTRODUCTION OF DRUG Rivaroxaban is chemically known as 5-Chloro-N-({(5S)-2-oxo-3-[4-(3-oxo-4- morpholinyl) phenyl]-1,3-oxazolidin-5-yl}methyl)-2thiophene carbox- mide. The molecular formula of Rivaroxaban is C 19 H 18 ClN 3 O 5 S and the molecular weight is g/mol. Rivaroxaban is an oral anticoagulant substance that prevents coagulation (clotting) of blood. It is an odorless, non-hygroscopic, white to yellowish powder and pure (S)- enantiomer. Rivaroxaban is an oral, direct Factor Xa inhibitor that has been shown to exhibit well-defined pharmacokinetic and pharmacodynamic properties, with high oral bioavailability [1]. It is invented and manufactured by Bayer and marketed as Xarelto [2]. Each Xarelto tablet contains 10 mg, 15 mg, or 20 mg of Rivaroxaban. The inactive ingredients of Xarelto are croscarmellose sodium, hypromellose, lactose monohydrate, magnesium stearate, microcrystalline cellulose, and sodium lauryl sulfate [3]. In the United States It is marketed by Janssen Pharmaceutica [4]. Rivaroxaban is the first available orally active direct factor Xa inhibitor from class of oxazolidinone derivative and it has been optimized for inhibiting both free factor Xa and factor Xa bound in the prothrombinase complex [5]. Rivaroxaban is indicated for the prevention of deep vein thrombosis which may lead to pulmonary embolism in patients undergoing knee or hip replacement surgery. The most common adverse reactions with Rivaroxaban are bleeding complications, including major bleeding events, fainting, itching, and muscle spasms have been reported [6]. The introduction of this drug in a surgical department represents a standard change, this drug is not administered preoperatively but postoperatively, and is not given subcutaneously but orally. Rivaroxaban inhibits free and fibrin-bound factor Xa as well as factor Xa in the prothrombinase complex, therefore it prevents clot formation and clot growth. Figure 1: Structural formula of Rivaroxaban 22
3 2.2 LITERATURE REVIEW The literature reviews regarding Rivaroxaban suggested that various analytical methods are reported for estimation of Rivaroxaban in bulk as well as in pharmaceutical formulations and in various biological fluids by using various analytical techniques such as HPLC, HPTLC and Spectrophometric method. The literature reviews regarding these methods are as under. a) Satyanarayana PV and Madhavi AS have been developed and validated RP HPLC method for the analysis of Rivaroxaban in pharmaceutical dosage form. The separation was achieved on symmetry C18 column. The isocratic mobile phase consisted THF: MeOH: ACN (10:40:50, v/v/v). The detection was monitored at 270nm with 1ml/min flow rate. The linear calibration curve was obtained in the concentration range between 10-40ppm with a coefficient of correlation [7]. b) Mustafa C, Tuba R, Engine K and Sacide A have reported validated RP-HPLC method for estimation of Rivaroxaban in pharmaceutical dosage forms. The separation was achieved by Phenomenex Luna C18 (250mm X 4.6mm, 5µm) column with 40 C column oven temperature. The isocratic elution was performed with ACN: water (55:45, v/v). The UV detection was achieved at 249nm wavelength with 1.2ml/min flow rate. The linear calibration curve was obtained in the concentration range between 5-40 ppm with a coefficient of correlation [8] c) Lories IB, Mostafa AA and Griges MA have developed HPLC, TLC densitometry, first derivative and first derivative ratio spectrophotometry method for determination of Rivaroxaban with alkaline degradation in bulk powder and tablets. The HPLC separation was achieved by C18 column with isocratic mobile phase consisted 1.2% w/v Potassium dihydrogen phosphate (ph 3.5) and ACN (70:30, v/v), ph was adjusted by using OPA. The flow rate was adjusted at 1.5ml/min with 20µl injection volume. The detection was monitored at 280 nm. The TLC separation was achieved by using chloroform-isobutyl alcohol (50:50, v/v) solvent system. The first derivative measurement of the drug was monitored at 237.4nm [9] 23
4 d) Pinaz AK and Muralikrishna KS have developed RP-HPLC method of Rivaroxaban with photolytic, acid and base degradation study. An isocratic separation was achieved using a Phenomenex C A (250mm 4.6mm, 5µm) column, with a flow rate of 1ml/min. The elution was monitored at 250nm with PDA detector. The mobile phase consisted of MeOH: ACN (50:50, v/v). The method was validated for specificity, linearity, precision, accuracy and robustness. The method was linear over the concentration range of µg/ml with r 2 = The drug substance was subjected to thermal and photolytic conditions [10][11][12] e) Chandrasekhar K, Satyavani P, Dhanalakshmi A, Devi ChLL, Anupama B and Narendra D have developed and validated RP-HPLC method for analysis of Rivaroxaban in formulations. The separation was achieved by using C-18 (250mm X 4.6mm, 5µm) column at ambient temperature with mobile phase consisted ACN: MeOH: 0.1% OPA (90:8:2, v/v/v) with the ph The flow rate was adjusted at 1.5ml/min and UV detection was performed at 234nm by UV detector. The linear calibration curve was obtained in the concentration range between ppm with a coefficient of correlation [13] f) Chandrabala S, Hima VB, Rupa MD and Sireesha A have developed and validated UV spectroscopic method for the determination of Rivaroxaban. The drug was estimated at 270 nm in DMSO. The linearity range was found between the concentration range 2 20 ppm with coefficient of correlation The regression equation is, Absorbance = X concentration of drug in µg/ml The apparent molar absorptivity and sandell s sensitivity were found to be L mol 1 cm 1 and µg cm 2, respectively [14]. g) Darshna V and Pinak P have reported HPTLC method with densitometry analysis for determination of Rivaroxaban from its tablet dosage form. The drug was spotted on silica gel F254 TLC plates under pure nitrogen stream by Linomat TLC spotter. Separation was carried out by using Methanol, Toluene, and Tri ethanolamine as mobile phase in ratio of (7:2.5:0.5,v/v/v). Developed TLC plates were scanned by CAMAG TLC 24
5 scanner and detection was carried out at 249nm. The Rf value of separated drug was found at The linearity curve of Rivaroxaban was observed in the concentration range between 500 to 3000ng/spot [15]. h) Schmitz EMH, Heuvel DV, Boonen K, Dongen JLJ, Brunsveld L and Kerkhof DV have developed the method for simultaneously determination of Dabigatran, Rivaroxaban and Apixaban using UPLC-MS/MS and comparison with coagulation assays for therapy monitoring. In this method plasma and full blood were spiked with Dabigatran, Rivaroxaban and Apixaban for a 6-point calibration (23-750ng/ml) with correlation coefficient No significant differences could be seen between plasma and full blood calibration lines. Additionally, no bias was found in spiked hemolytic, icteric and lipemic plasma. Stability tests showed adequate stability during three freeze-thaw cycles, 24-hours plasma storage at 20 C and 8-day sample storage at 4 C. Specificity of the UPLC-MS/MS was good and LLOD and LLOQ were <1ng/mL for all three drugs. For Dabigatran, Rivaroxaban and Apixaban, the relative recovery was 73%, 78% and 104%, respectively. This was considered acceptable, due to the addition of the internal standards. Acceptance criteria for accuracy and precision were applied as given by the FDA (100±15% and <15%, respectively) [16]. i) Pinaz AK and Muralikrishna KS have design dissolution profile of Rivaroxaban with validation by using RP-HPLC in dosage form. The conditions established for dissolution were: 900ml of Acetate buffer (ph 4.5) and 0.2 % SLS as dissolution medium, using a paddle type dissolution apparatus at a stirring rate of 75rpm which was able to give drug release of 98.86%. The drug release was evaluated by RP-HPLC method at 250nm and a good linearity was observed in the concentration range of 20-60µg/mL with correlation coefficient of The percentage recovery of Rivaroxaban was found to be The %CV (0.22%; n=6) indicated a good precision of the analytical method. Robustness of the method was performed by using different rotation speeds and temperatures. The validation parameters included linearity, accuracy, precision and robustness [17] 25
6 j) Pinaz AK and Muralikrishna KS have noted spectrophotometric method for determination of Rivaroxaban simultaneously for bulk and tablet formulation. The study was conducted in MeOH between the wavelengths of nm. The developed method was linear in the concentration range of 2-12µg/ml with correlation coefficient and respectively for bulk and tablet dosage form. The drug recovery was 99.31% in bulk drug analysis and in tablet dosage form it was %. The LOD were found at 0.059µg/ml and µg/ml, The LOQ were found 0.179µg/ml and 0.298µg/ml respectively for bulk and tablet dosage form [18][19]. k) Satyanarayana PVV and Madhavi AS have reported spectrophotometric method validation for determination of Rivaroxaban in bulk and tablet formulation. In this proposed research work five spectrophotometric methods such as 2-2 Bipyridine method (M1), 4-Amino phenazone method (M2), Haematoxylin method (M3), Iso nicotanic hydrazide method (M4), Naptha quinone sulphate method (M5) have been developed and applied for routine determination of Rivaroxaban in pharmaceutical formulations and bulk dosage forms. These methods are based on the color formation of the drug on binding with the different reagents. All these method have different linearity ranges between 2-12, 3-21, 30-90, 5-30 and 15-90ppm respectively for M1, M2, M3, M4 and M5 methods. The recovery of drugs were found %, 99.61%, %, 99.94% and % respectively for M1, M2, M3, M4 and M5 methods [20]. l) Rohde G has reported HPLC MS/MS method for determination of Rivaroxaban in human plasma. After precipitation of plasma proteins with methanol containing the internal standard followed by centrifugation, the plasma supernatant was injected directly onto the HPLC MS/MS system. The concentrations could be determined between µg/l. The Inter-assay precision was 7.4% and inter-assay accuracy was between 96.3 and 102.9% throughout the entire working range [21]. m) Vijayabhaskar N and Sekhar reddy BC have reported a novel RP-HPLC method for the quantification of Rivaroxaban in formulations. The Isocratic elution was achieved on a Kromasil C18 (250mmx4.6mm, 5µm) column with a flow rate of 1ml/min and at 26
7 ambient temperature. The mobile phase consisted of MeOH: ACN (80:20, v/v) (ph 4.4). The UV detection wavelength was maintained at 273nm with 20µl injection volumn. The percentage RSD for precision and accuracy of the developed method was found to be less than 2% [22]. 2.3 AIM OF PRESENT WORK The literature survey indicates, there are many methods are available for the estimation of Rivaroxaban as a drug substance as well as in pharmaceutical dosage form, few of the methods are also available which deals with the bioanalytical study. But all of these are not stability indicating. Most of the reported methods either do not include stress degradation studies or are not completely validated and they are time consuming and expensive. Furthermore these methods are not impressionable to achieve the high throughput study which can be possible by optimizing the method in such a way which includes shortest run time with maximum selectivity. The primary object of the present work was to develop and validate a stability indicating HPLC method for estimation of Rivaroxaban under stress condition such as acid and base hydrolysis, oxidative, thermal and photolytic conditions. Hence, it can be maximum utilize for the analysis of formulation development and stability testing as well as at quality control laboratory for routine use. The aim and scope of the proposed work are, to develop rapid and simplest RP-HPLC method for quantification and estimation of the drug substance with highest selectivity. To perform stress degradation study for confirm the stability of the drug substance. The analytical method validation for the proposed method was performed as per ICH guideline [23][24][25]. 2.4 EXPERIMENTAL CONDITION Materials The Reference standard of Rivaroxaban was provided as a gift sample for research purpose by Anlon Research Organization, Rajkot, India and tablet dosage form was purchased from local market. HPLC grade Acetonitrile was purchased from Merck India Limited, Mumbai, India and HPLC grade Orthophosphoric acid was obtained from Spectrochem Mumbai, India. Analytical grade Hydrochloric acid, Sodium hydroxide 27
8 pellets and Hydrogen peroxide were purchased from Ranbaxy fine chemicals, New Delhi, India. High purity deionised water was obtained from Milli-Q (Millipore, Miliford, MA, USA) purification system µm membrane filters were purchased from Pall Life Sciences, Mumbai, India and nylon syringe filters 0.45 µm were purchased from Millex- Hn, Mumbai, India Instrumentation Chromatographic separation was carried out using a HPLC system (Waters 2489, miliford, USA), consisted a quaternary gradient pump (TM 600), Rheodyne manual injector with 20µl loop, column oven and UV detector employed for analysis. The output signal was monitored and processed by Empower 2.0 version software. A microbalance obtained by LCGC Radwag weighing solution Pvt. Ltd. Mumbai, India, An ultra sonic water bath SONICA from Spincotech Pvt. Ltd. Mumbai, India and ph meter LI 610 ELICO Mumbai, India were also used Chromatographic condition The chromatographic analysis was performed by Phenomenax C8 100A (250mm X 4.6mm id, 5µm particle size) column with 30 C column oven temperature. The isocratic mobile phase was consisted 0.1% OPA: ACN (60:40, v/v) and the detection were monitored at wavelength of 280nm. The flow rate was adjusted at 1ml/min with 20µl injection volume. The total analysis time was selected 15minute Mobile phase preparation The mobile phase was consisted 0.1% Orthophosphoric acid and Acetonitrile (60:40, v/v), before use degassed the mobile phase by ultrasonic bath Diluent preparation Water: Methanol (50:50, v/v) used as a diluent Stock solution preparation The stock solution of 500µg/ml Rivaroxaban was prepared by dissolving accurately weighted 50mg of Rivaroxaban working standard in 100ml volumetric flask. Add 50ml of diluent (water: MeOH (50:50, v/v)) to 100ml volumetric flask and dissolve the 28
9 substance by sonication about 10 to 15 minute. The solution was dilute up to mark with diluent. For standard solution preparation pipette out 5ml of above stock solution into 50ml volumetric flask and dilute up to the mark with diluent. This solution contains 50µg/ml Rivaroxaban Test solution preparation The preparation of 500µg/ml stock solution, twenty tablets were accurately crushed, weighted and average weight has been calculated. The portion of powder equivalent to the weight of five tablets has been taken and transferred to a 100ml volumetric flask. Add 50ml of diluent (water: MeOH (50:50, v/v)) to the flask and dissolve the substance by sonication around 10 to 15 minute. The solution was dilute up to mark with diluent. Filter the solution with 0.45µm membrane filter. For test solution preparation pipette out 5ml of above stock solution into 50ml volumetric flask and dilute up to the mark with diluent. This solution contains 50µg/ml Rivaroxaban. 2.5 RESULT AND DISCUSSION Development and optimization of the HPLC method This chapter describes assay method development and validation of Rivaroxaban tablet with forced degradation study. For accurate, precise and robust method development, the analytical conditions were selected after testing the different parameters that influence LC analysis, such as analytical column, detection wavelength, aqueous and organic mobile phase, mobile phase proportion, analyte concentration, injection volume, flow rate and other factors were exhaustively studied. Phenomenax C8 100A (250mm X 4.6mm id, 5µm particle size) column was used because of its advantages of high degree of retention, high resolution capacity, better reproducibility, ability to produce lower back pressure and low degree of tailing. For mobile phase selection, the preliminary trials using different compositions of mobile phases consisting of water and ACN (50:50, v/v) gave poor peak shape. The representative chromatogram for the same is shown as under. 29
10 Figure 2: Chromatogram of standard preparation [water: ACN (50: 50v/v)] Above chromatogram clearly indicate that the peak is not symmetrical and value of theoretical plates is lower side. In focus to develop good symmetrical peak, water was replaced by 0.1% OPA. Thus, better peak shape was obtained. The representative chromatogram for the same is shown as under Figure 3: Chromatogram of standard preparation [0.1% OPA: ACN (50:50, v/v)] Further, the mobile phase proportion was optimized to retain analyte properly that provide good resolution between Rivaroxaban and its degradation impurities. Proportion of ACN is finalized to 40% of the mobile phase. The detection wavelength was decided after screened the standard solution over nm using the advantage of photo diode array detector. On the basis of peak absorption maxima and peak purity index, the 280nm was decided as the detection wavelength which was provided the maximum chromatographic compatibility to the method. As a diluent the mixture of water-methanol (50:50, v/v) was made. Injection volume was fixed to 20µl and the flow rate of the 30
11 mobile phase was set to 2ml/min. On this finalized chromatographic condition, obtained chromatogram was having of good peak symmetry and higher theoretical plates. The representative chromatogram for the same is shown as under Figure 4: Chromatogram of standard preparation [0.1% OPA: ACN (60:40, v/v)] Figure 5: Chromatogram of test preparation [0.1% OPA: ACN (60:40, v/v)] The drug substance was easily extracted from pharmaceutical dosage using diluent as water-meoh (50:50, v/v). Tablet was easily isolated using water and MeOH. The drug substance is freely to very soluble in MeOH. Extraction trials are finalized to keep sonication time for around minute. Solutions of standard preparation and test preparation were found stable in diluent. All validation parameters were performed by taking same diluent concentration Stress degradation study Degradation study was performed by transferring powdered tablets equivalent to 50mg Rivaroxaban into 250ml round bottom flask. Then prepared samples were employed for 31
12 acidic, alkaline, oxidative, thermal and photolytic conditions. After the degradation treatments were completed, the stress content solutions were allowed to equilibrate to room temperature and diluted with mobile phase to attain 50µg/ml concentrations of Rivaroxaban. The placebo was also subjected to same stress conditions to identify any response due to the forced degradation conditions. Specific conditions were described as follow. a) Acidic condition Acidic degradation study was performed by heating the drug content with 20ml 0.5N HCl at 50ºC for 30 minute. After heating equilibrate the solution at room temperature and the mixture was neutralized with 0.5N NaOH solutions. Further the mixture was diluted with diluents to achieve 50µg/ml drug concentration. The resulting chromatogram obtained by acidic degradation described the drug was degraded around 13%. The major impurity peak was found at 3.6 minute and the degradation product resulting from the stress studies did not interfere with the detection of Rivaroxaban Figure 6: Chromatogram obtained by acidic stress degradation study b) Alkali condition Alkaline degradation study was performed by heating the drug content with 10ml 0.01N NaOH for 20 minutes at 60ºC. After heating equilibrate the solution at room temperature and the mixture was neutralized with 0.01N HCl solutions. Further the mixture was diluted with diluents to achieve 50µg/ml drug concentration. The resulting chromatogram obtained by alkali degradation described the major degradation was found in alkali condition and the drug was degraded up to 50%. The major impurity peak was found at 32
13 2.5 minute and the degradation products resulting from the stress studies did not interfere with the detection of Rivaroxaban Figure 7: Chromatogram obtained by alkali stress degradation study c) Oxidative condition Oxidation degradation study was performed by heating the drug content with 30% (v/v) H 2 O 2 at 80 C for 90 minute. Further the mixture was diluted with diluents to achieve 50µg/ml drug concentration. The resulting chromatogram obtained by oxidative degradation described the drug was degraded around 6% and separate degraded product was not found by thermal degradation Figure 8: Chromatogram of oxidative stress degradation study d) Thermal condition Thermal degradation was performed by exposing solid drug at 80ºC for 36 hour in hot air oven. The resulting chromatogram obtained by thermal degradation described the drug 33
14 was degraded around 3% and separate degraded product was not found by thermal degradation Figure 9: Chromatogram obtained by thermal stress degradation study e) Photolytic condition Photolytic degradation study was performed by exposing powder drug directly to sunlight for 72 hour (day hour). It was found that around 1.5% of the drug was degrading in photolytic condition and separate degraded product was not found by photolytic degradation Figure 10: Chromatogram of photolytic stress degradation study From the above chromatogram it can be concluded that there is no interference of any degradation product to the peak of interest and impurity has been generated by each stress condition. 34
15 2.5.3 Method validation parameters The developed LC method for determination of Rivaroxaban in bulk drug as well as in pharmaceutical dosage form is further validated as per ICH guidelines. The method was validated by several validation parameters such as Accuracy, Precision, Linearity, Limit of Detection, Limit of Quantitation, Robustness and Specificity. Whole validation was performed as per ICH guideline Q2A, Q2B and Q2(R1) [23][24][25] to ensuring that the present method was suitable for its intended purpose Specificity study The specificity of the method was evaluated by checking the interference of placebo components with drug. The additives of tablet are practically insoluble in diluent whereas the active pharmaceutical ingredients are freely soluble. So, the active pharmaceutical ingredient is easily isolated from placebo. Further the specificity of the method toward the drug was established by means of the interference of diluent at the retention time of the drug peak, and the specificity of the method toward the drug was also established by means of the interference of the degradation products against drug during the forced degradation study. From the specificity experiment and subsequently achieved chromatograms it has proven that any interference was not observed from blank or placebo to the peak of interest, Hence it authenticate there was no interference of any peak of degradation product with drug peak. So, the proposed method is highly specific with respect to the diluent and excipients in the commercial sample. Data for standard preparation Data for test preparation Replicate Area Replicate Area Average Standard weight (mg) Test weight (mg) Mean Mean test weight (mg) Stdv Label claim 10 % RSD 0.32 % Assay Table 1: Specificity study standard and test preparation data 35
16 Figure 11: Chromatogram of diluent obtained by specificity experiment Figure 12: Chromatogram of placebo obtained by specificity experiment Figure 13: Chromatogram of test preparation obtained by specificity experiment Prototype calculation formula for relative standard deviation is as under: % #$%= $&'()'*) )+,-'&-.( /+'(,'
17 % #$%= % #$%=0.32 Prototype calculation formula for assay determination is as under: % ;<<'== ;> ;$ 2?$?> 2 B %;<<'== % ;<<'== Where, AT = Average Area of Test Preparation. AS = Average Area of Standard Preparation. WS = Weight of Working Standard (mg). WT = Weight of Test Sample (mg). AW = Average Weight of Formulation (mg). LC = Label Claim Weight of Formulation (mg). P = Potency of Working Standard (%) Linearity study The linearity study was determined by analyzing seven solutions in the concentration range between 20-80µg/ml (20, 30, 40, 50, 60, 70 and 80µg/ml of Rivaroxaban). These concentration levels were respectively corresponding to 40, 60, 80, 100, 120, 140 and 160% of test solution concentration. The plot of peak areas against concentration data were evaluated by linear regression analysis. The response of the drug was found to be linear in the investigation and the correlation coefficient of the linearity study was with linear regression equation y=21577x , where y is the peak area in absorbance units; x is the concentration in µg/ml. which proves the method is highly linear over the working range between 20-80µg/ml. 37
18 Data for standard preparation Replicate Standard peak area Mean Std. dev % RSD 0.12 Table 2: Linearity study standard preparation Linearity Level Replicate Area Mean area Level (40%) Level (60%) Level (80%) Level (100%) Level (120%) Level (140%) Level (160%) Table 3: Linearity study level preparation data 38
19 Concentration level (%) Volume of linearity stock solution taken (ml) Diluted to (ml) Final concentration (µg/ml) Correlation co-efficient Slope Intercept Mean area Table 4: Linearity study concentration Vs peak area response data X axis = Concentration (µg/ml), Y axis = Peak Area in absorbance units Chart 1: Linearity curve for Rivaroxaban 39
20 Figure 14: Chromatogram of linearity level-1 (40%) Figure 15: Chromatogram of linearity level-2 (60%) Figure 16: Chromatogram of linearity level -3 (80%) 40
21 Figure 17: Chromatogram of linearity level-4 (100%) Figure 18: Chromatogram of linearity level-5 (120%) Figure 19: Chromatogram of linearity level-6 (140%) 41
22 Figure 20: Chromatogram of linearity level-7 (160%) Prototype calculation formula for relative standard deviation is as under: % #$%= $&'()'*) )+,-'&-.( /+'(,' % #$%= % #$%= Limit of Detection & Limit of Quantitation study LOD is the lowest amount of the drug content which can be detected by the proposed method while LOQ is the lowest amount which can be quantified by the method. The guideline suggest minimum signal to noise ratio (S/N) more than 3.3 for LOD and more than 10 for LOQ. The LOD and LOQ concentrations were found at 0.08µg/ml and 0.175µg/ml respectively. It has been established by evaluating the minimum level at which the analyte could be readily detected and quantified accurately. On the basis of linearity data theoretically it can be also calculated by the given formula. LOD = 3.3(σ /S) LOQ = 10(σ /S) Where, σ = Standard deviation of regression line S = Slope of the calibration curve 42
23 All the results of LOD and LOQ data were within the acceptance criteria, hence it can be conclude that the LOD and LOQ of the method was 0.08µg/ml and 0.175µg/ml respectively which correspond to 0.16% and 0.35% of working concentration. Data for standard preparation Data for LOQ preparation Replicate Peak area Replicate Peak area Mean Mean 4015 Stdev Stdev % RSD 0.33 % RSD 1.11 Table 5: LOQ and standard preparation data Linearity level Concentration level (%) Final concentration (µg/ml) Mean area 1 LOQ Correlation co-efficient Slope Intercept Table 6: LOQ study by evaluating linearity up to LOQ concentration LOQ of the analytical method can evaluated by establish linearity up to LOQ value. Hence linearity study is extended to LOQ value, 43
24 X axis = Concentration (µg/ml) Y axis = Peak Area Chart 2: Regression analysis chart of linearity study included with LOQ level Figure 21: Chromatogram obtained by limit of detection study 44
Research Article. Stress study and estimation of a potent anticoagulant drug rivaroxaban by a validated HPLC method: Technology transfer to UPLC
Available online www.jocpr.com Journal of Chemical and Pharmaceutical Research, 2015, 7(10):65-74 Research Article ISSN : 0975-7384 CODEN(USA) : JCPRC5 Stress study and estimation of a potent anticoagulant
More informationDevelopment of validated RP- HPLC method for estimation of rivaroxaban in pharmaceutical formulation
IJPAR Vol.4 Issue 4 Oct Dec - 2015 Journal Home page: ISSN: 2320-2831 Research Article Open Access Development of validated RP- HPLC method for estimation of rivaroxaban in pharmaceutical formulation V.
More informationPVV Satyanaryana et al., IJSID, 2012, 2 (1), 226-231. International Journal of Science Innovations and Discoveries
ISSN:2249-5347 IJSID International Journal of Science Innovations and Discoveries An International peer Review Journal for Science Research Article Available online through www.ijsidonline.info RP-HPLC
More informationSIMULTANEOUS DETERMINATION OF TELMISARTAN AND HYDROCHLOROTHIAZIDE IN TABLET DOSAGE FORM USING REVERSE PHASE HIGH PERFORMANCE LIQUID CHROMATOGRAPHY
CHAPTER 5 SIMULTANEOUS DETERMINATION OF TELMISARTAN AND HYDROCHLOROTHIAZIDE IN TABLET DOSAGE FORM USING REVERSE PHASE HIGH PERFORMANCE LIQUID CHROMATOGRAPHY CHAPTER 5 Simultaneous determination of Telmisartan
More informationReversed Phase High Presssure Liquid Chromatograhphic Technique for Determination of Sodium Alginate from Oral Suspension
International Journal of PharmTech Research CODEN (USA): IJPRIF ISSN : 0974-4304 Vol.2, No.2, pp 1634-1638, April-June 2010 Reversed Phase High Presssure Liquid Chromatograhphic Technique for Determination
More informationPhotolytic-Thermal Degradation Study And Method Development Of Rivaroxaban By RP-HPLC
International Journal of PharmTech Research CODEN (USA): IJPRIF ISSN : 0974-4304 Vol.5, No.3, pp 1254-1263, July-Sept 2013 Photolytic-Thermal Degradation Study And Method Development Of Rivaroxaban By
More informationInternational Journal of Research and Reviews in Pharmacy and Applied science. www.ijrrpas.com
International Journal of Research and Reviews in Pharmacy and Applied science www.ijrrpas.com P.V.V.Satyanarayana*, Alavala Siva Madhavi NEW SPECTROPHOTOMETRIC METHODS FOR THE QUANTITATIVE ESTIMATION OF
More informationA NEW METHOD DEVELOPMENT AND VALIDATION FOR ANALYSIS OF RIVAROXABAN IN FORMULATION BY RP HPLC
A NEW METHOD DEVELOPMENT AND VALIDATION FOR ANALYSIS OF RIVAROXABAN IN FORMULATION BY RP HPLC K.Chandra sekhar, P. Satya vani, A. Dhana lakshmi, Ch.LL.Devi, Anupama Barik, Narendra Devanaboyina * Department
More informationHigh Performance Thin Layer Chromatographic Method for Estimation of Cefprozil in Tablet Dosage Form
ISSN: 0973-4945; CODEN ECJHAO E- Chemistry http://www.e-journals.net Vol. 5, No.3, pp. 427-430, July 2008 High Performance Thin Layer Chromatographic Method for Estimation of Cefprozil in Tablet Dosage
More informationINTERNATIONAL JOURNAL OF PHARMACEUTICAL RESEARCH AND BIO-SCIENCE
Rajgor VM,, 2014; Volume 3(3): 188-197 INTERNATIONAL JOURNAL OF PHARMACEUTICAL RESEARCH AND BIO-SCIENCE ANALYTICAL METHOD DEVELOPEMENT AND VALIDATION FOR THE SIMULTANEOUS ESTIMATION OF MEMANTINE HCL AND
More informationStep-by-Step Analytical Methods Validation and Protocol in the Quality System Compliance Industry
Step-by-Step Analytical Methods Validation and Protocol in the Quality System Compliance Industry BY GHULAM A. SHABIR Introduction Methods Validation: Establishing documented evidence that provides a high
More informationGuidance for Industry
Guidance for Industry Q2B Validation of Analytical Procedures: Methodology November 1996 ICH Guidance for Industry Q2B Validation of Analytical Procedures: Methodology Additional copies are available from:
More informationVALIDATION OF ANALYTICAL PROCEDURES: TEXT AND METHODOLOGY Q2(R1)
INTERNATIONAL CONFERENCE ON HARMONISATION OF TECHNICAL REQUIREMENTS FOR REGISTRATION OF PHARMACEUTICALS FOR HUMAN USE ICH HARMONISED TRIPARTITE GUIDELINE VALIDATION OF ANALYTICAL PROCEDURES: TEXT AND METHODOLOGY
More informationSUCRALOSE. White to off-white, practically odourless crystalline powder
SUCRALOSE Prepared at the 41st JECFA (1993), published in FNP 52 Add 2 (1993). Metals and arsenic specifications revised at the 63rd JECFA (2004). An ADI of 0-15 mg/kg bw was established at the 37th JECFA
More informationHigh performance thin layer chromatographic method for estimation of deflazacort in tablet
ISSN: 2231-3354 Received on: 07-09-2011 Revised on: 11-09-2011 Accepted on: 13-09-2011 High performance thin layer chromatographic method for estimation of deflazacort in tablet Patel Satish A and Patel
More informationANALYTICAL METHODS INTERNATIONAL QUALITY SYSTEMS
VALIDATION OF ANALYTICAL METHODS 1 GERT BEUVING INTERNATIONAL PHARMACEUTICAL OPERATIONS TASKS: - Internal auditing - Auditing of suppliers and contract manufacturers - Preparing for and guiding of external
More informationHIGH PERFORMANCE THIN LAYER CHROMATOGRAPHIC METHOD FOR DETERMINATION OF TADALAFIL IN TABLET DOSAGE FORM
Volume 1, Issue 3, 2011. ISSN: 2249-3387 Journal home page: http://www.ajptr.com/ HIGH PERFORMANCE THIN LAYER CHROMATOGRAPHIC METHOD FOR DETERMINATION OF TADALAFIL IN TABLET DOSAGE FORM Satish A. Patel
More informationHPLC Analysis of Acetaminophen Tablets with Waters Alliance and Agilent Supplies
HPLC Analysis of Acetaminophen Tablets with Waters Alliance and Agilent Supplies Application Note Small Molecule Pharmaceuticals Authors Jignesh Shah, Tiantian Li, and Anil Sharma Agilent Technologies,
More information+++#,# & %!"#$%& '"#()*
+++#,#! "#$#%&"##$!'#&("&!"# $ %& %& & %!"#$%& '"#()* +++#,# Research Article Chemistry International Journal of Pharma and Bio Sciences ISSN 0975-6299 A NOVEL RP-HPLC METHOD FOR THE QUANTIFICATION OF
More informationInternational Journal of Pharma and Bio Sciences V1(2)2010
1 Central Drugs Laboratory,Kolkata Angshuman Biswas 1 and Arindam Basu 1 *Corresponding author bangshuman@rediffmail.com ABSTRACT A fast and reliable high performance liquid chromatography method for determination
More informationSimultaneous determination of L-ascorbic acid and D-iso-ascorbic acid (erythorbic acid) in wine by HPLC and UV-detection (Resolution Oeno 11/2008)
Method OIV-MA-AS313-22 Type II method Simultaneous determination of L-ascorbic acid and D-iso-ascorbic acid (erythorbic acid) in wine by HPLC and UV-detection (Resolution Oeno 11/2008) 1. Introduction
More informationLUMEFANTRINE Draft proposal for The International Pharmacopoeia (October 2006)
October 2006 RESTRICTED LUMEFANTRINE Draft proposal for The International Pharmacopoeia (October 2006) DRAFT FOR DISCUSSION World Health Organization 2006 All rights reserved. This draft is intended for
More informationERDOSTEINE - MONOGRAPH.
STRUCTURAL FORMULA (±1S-(2-[N-3-(2-oxotetrahydro thienyl)]acetamido)-thioglycolic acid) C 8 H 11 NO 4 S 2 M.W. = 249.307 DESCRIPTION Color : White to ivory white Appearance : Microcrystalline powder SOLUBILITY
More informationDevelopment and validation of UV spectrophotometric method for the determination of rivaroxaban
Available online at www.derpharmachemica.com Scholars Research Library Der Pharma Chemica, 013, 5(4):1-5 (http://derpharmachemica.com/archive.html) ISSN 0975-413X CODEN (USA): PCHHAX Development and validation
More informationAnalytical Test Report
Analytical Test Report Customer: Address (City, State): Purchase Order: Report Number: Project Number: Date Received: Date of Report: Test Location: Boulder, CO. Assay: Part Number: Amino Acids by HPLC
More informationTamsulosin Hydrochloride Capsules
. nal Revision Bulletin Official October 1, 2011 Tamsulosin 1 standard solution, and shake well. Centrifuge at 1500 rpm for 10 min, and use the supernatant, passing it if Tamsulosin Hydrochloride Capsules
More informationJournal of Chemical and Pharmaceutical Research
Available on line www.jocpr.com Journal of Chemical and Pharmaceutical Research ISSN No: 0975-7384 CODEN(USA): JCPRC5 J. Chem. Pharm. Res., 2010, 2(6):62-67 Development and validation of RP- HPLC method
More informationLC-MS/MS Method for the Determination of Docetaxel in Human Serum for Clinical Research
LC-MS/MS Method for the Determination of Docetaxel in Human Serum for Clinical Research J. Jones, J. Denbigh, Thermo Fisher Scientific, Runcorn, Cheshire, UK Application Note 20581 Key Words SPE, SOLA,
More informationStability-indicating High Performance Thin Layer Chromatographic Determination of Clozapine in Tablet Dosage Form
Stability-indicating High Performance Thin Layer Chromatographic Determination of Clozapine in Tablet Dosage Form Zahid Zaheer *, Mazhar Farooqui 1, S.R.Dhaneshwar 2 *Y.B.Chavan College of Pharmacy, Dr.
More informationDevelop a Quantitative Analytical Method for low (» 1 ppm) levels of Sulfate
Cantaurus, Vol. 7, 5-8, May 1999 McPherson College Division of Science and Technology Develop a Quantitative Analytical Method for low (» 1 ppm) levels of Sulfate Janet Bowen ABSTRACT Sulfate is used in
More informationJournal of Chemical and Pharmaceutical Research
Available on line www.jocpr.com Journal of Chemical and Pharmaceutical Research J. Chem. Pharm. Res., 2010, 2(1): 91-99 ISSN No: 0975-7384 A Stability-Indicating RP-LC method for the Determination of Related
More informationUV-VIS SPECTROPHOTOMETRIC METHOD FOR ESTIMATION OF GABAPENTIN AND METHYLCOBALAMIN IN BULK AND TABLET
International Journal of ChemTech Research CODEN( USA): IJCRGG ISSN : 0974-4290 Vol.2, No.1, pp 695-699, Jan-Mar 2010 UV-VIS SPECTROPHOTOMETRIC METHOD FOR ESTIMATION OF GABAPENTIN AND METHYLCOBALAMIN IN
More informationEUROPEAN COMMISSION DIRECTORATE-GENERAL TAXATION AND CUSTOMS UNION TAX POLICY Excise duties and transport, environment and energy taxes
EUROPEAN COMMISSION DIRECTORATE-GENERAL TAXATION AND CUSTOMS UNION TAX POLICY Excise duties and transport, environment and energy taxes Brussels, 18th May 2005 CED No 494 rev 2 Final TAXUD/3711/2004 POETRY:
More informationRao, et al., Int J Res Pharm Sci 2015, 5(2) ; 17 24. Available online at www.ijrpsonline.com. Research Article
International Journal of Research in Pharmacy and Science Available online at www.ijrpsonline.com Research Article Stability-indicating UPLC method for determining related substances and degradants in
More informationICH Topic Q 2 (R1) Validation of Analytical Procedures: Text and Methodology. Step 5
European Medicines Agency June 1995 CPMP/ICH/381/95 ICH Topic Q 2 (R1) Validation of Analytical Procedures: Text and Methodology Step 5 NOTE FOR GUIDANCE ON VALIDATION OF ANALYTICAL PROCEDURES: TEXT AND
More informationAnalytical Specifications RIVAROXABAN
Page 1 of 9 ANALYTE NAME AND STRUCTURE - RIVAROXABAN SYNONYMS Xarelto CATEGORY Anticoagulant TEST CODE PURPOSE Therapeutic Drug Monitoring GENERAL RELEVANCY BACKGROUND Xarelto (rivaroxaban) is an orally
More informationResearch Article. Development and validation of a HPLC analytical assay method for dapoxetine tablets: A medicine for premature ejaculation
Available online www.jocpr.com Journal of Chemical and Pharmaceutical Research, 2014, 6(7):1613-1618 Research Article ISSN : 0975-7384 CODEN(USA) : JCPRC5 Development and validation of a HPLC analytical
More informationSIMULTANEOUS DETERMINATION OF NALTREXONE AND 6- -NALTREXOL IN SERUM BY HPLC
SIMULTANEOUS DETERMINATION OF NALTREXONE AND 6- -NALTREXOL IN SERUM BY HPLC Katja SÄRKKÄ, Kari ARINIEMI, Pirjo LILLSUNDE Laboratory of Substance Abuse, National Public Health Institute Manerheimintie,
More informationBy T.Sudha, T.Raghupathi
Global Journal of Medical research Volume 11 Issue 2 Version 1.0 Type: Double Blind Peer Reviewed International Research Journal Publisher: Global Journals Inc. (USA) Online ISSN: 0975-5888 Reverse Phase
More informationIN VITRO BINDING BIOEQUIVALENCE STUDY SUMMARY TABLES AND SAS TRANSPORT FORMATTED TABLES FOR DATASET SUBMISSION
IN VITRO BINDING BIOEQUIVALENCE STUDY SUMMARY TABLES AND SAS TRANSPORT FORMATTED TABLES FOR DATASET SUBMISSION I. For Calcium Acetate Drug Products Table I.1 Submission Summary * Drug Product Name Strength(s)
More informationQuality by Design Approach for the Separation of Naproxcinod and its Related Substances by Fused Core Particle Technology Column
Journal of Chromatographic Science Advance Access published October 11, 2012 Journal of Chromatographic Science 2012;00:1 7 doi:10.1093/chromsci/bms162 Article Quality by Design Approach for the Separation
More informationApplying Statistics Recommended by Regulatory Documents
Applying Statistics Recommended by Regulatory Documents Steven Walfish President, Statistical Outsourcing Services steven@statisticaloutsourcingservices.com 301-325 325-31293129 About the Speaker Mr. Steven
More informationIntelligent use of Relative Response Factors in Gas Chromatography-Flame Ionisation Detection
52 May/June 2012 Intelligent use of Relative Response Factors in Gas Chromatography-Flame Ionisation Detection by Karen Rome and Allyson McIntyre, AstraZeneca, Macclesfield, SK10 2NA, UK Quantitative analysis
More informationGUIDELINES FOR THE VALIDATION OF ANALYTICAL METHODS FOR ACTIVE CONSTITUENT, AGRICULTURAL AND VETERINARY CHEMICAL PRODUCTS.
GUIDELINES FOR THE VALIDATION OF ANALYTICAL METHODS FOR ACTIVE CONSTITUENT, AGRICULTURAL AND VETERINARY CHEMICAL PRODUCTS October 2004 APVMA PO Box E240 KINGSTON 2604 AUSTRALIA http://www.apvma.gov.au
More informationApplication Note. Determination of Nitrite and Nitrate in Fruit Juices by UV Detection. Summary. Introduction. Experimental Sample Preparation
Application Note Determination of Nitrite and Nitrate in Fruit Juices by UV Detection Category Food Matrix Fruit Juice Method HPLC Keywords Ion pair chromatography, fruit juice, inorganic anions AZURA
More informationOverview. Purpose. Methods. Results
A ovel Approach to Quantify Unbound Cisplatin, Carboplatin, and xaliplatin in Human Plasma Ultrafiltrate by Measuring Platinum-DDTC Complex Using LC/M/M Min Meng, Ryan Kuntz, Al Fontanet, and Patrick K.
More informationThe Use of Micro Flow LC Coupled to MS/MS in Veterinary Drug Residue Analysis
The Use of Micro Flow LC Coupled to MS/MS in Veterinary Drug Residue Analysis Stephen Lock AB SCIEX Warrington (UK) Overview A rapid, robust, sensitive and specific LC-MS/MS method has been developed for
More informationTransfer of a USP method for prednisolone from normal phase HPLC to SFC using the Agilent 1260 Infinity Hybrid SFC/UHPLC System Saving time and costs
Agilent Application Solution Transfer of a USP method for prednisolone from normal phase PLC to SFC using the Agilent 126 Infinity ybrid SFC/UPLC System Saving time and costs Application Note Pharmaceutical
More informationANALYSIS OF FOOD AND NATURAL PRODUCTS LABORATORY EXERCISE
ANALYSIS OF FOOD AND NATURAL PRODUCTS LABORATORY EXERCISE Determination of carbohydrates in foodstuff (LC/RID method) Exercise guarantor: Assoc. Prof. Karel Cejpek, Ph.D. CONTENT Required knowledge...
More informationLiquid Chromatographic Method for the estimation of Donepezil Hydrochloride in a Pharmaceutical Formulation
International Journal of ChemTech Research CODEN( USA): IJCRGG ISSN : 0974-4290 Vol.3, No.1, pp 112-118, Jan-Mar 11 Liquid Chromatographic Method for the estimation of Donepezil Hydrochloride in a Pharmaceutical
More informationI. ACID-BASE NEUTRALIZATION, TITRATION
LABORATORY 3 I. ACID-BASE NEUTRALIZATION, TITRATION Acid-base neutralization is a process in which acid reacts with base to produce water and salt. The driving force of this reaction is formation of a
More informationSPE, LC-MS/MS Method for the Determination of Ethinyl Estradiol from Human Plasma
SPE, LC-MS/MS Method for the Determination of Ethinyl Estradiol from uman Plasma Krishna Rao Dara, Dr. Tushar N. Mehta, Asia Pacific Center of Excellence, Thermo Fisher Scientific, Ahmedabad, India Application
More informationAnalytical Test Method Validation Report Template
Analytical Test Method Validation Report Template 1. Purpose The purpose of this Validation Summary Report is to summarize the finding of the validation of test method Determination of, following Validation
More informationAnalysis of the Vitamin B Complex in Infant Formula Samples by LC-MS/MS
Analysis of the Vitamin B Complex in Infant Formula Samples by LC-MS/MS Stephen Lock 1 and Matthew Noestheden 2 1 AB SCIEX Warrington, Cheshire (UK), 2 AB SCIEX Concord, Ontario (Canada) Overview A rapid,
More informationJournal of Chemical and Pharmaceutical Research, 2012, 4(7):3483-3488. Research Article
Available online www.jocpr.com Journal of Chemical and Pharmaceutical Research, 2012, 4(7):3483-3488 Research Article ISSN : 0975-7384 CODEN(USA) : JCPRC5 Simultaneous UV spectrphotometric estimation of
More informationα-cyclodextrin SYNONYMS α-schardinger dextrin, α-dextrin, cyclohexaamylose, cyclomaltohexaose, α- cycloamylase
α-cyclodextrin New specifications prepared at the 57th JECFA (2001) and published in FNP 52 Add 9 (2001). An ADI not specified was established at the 57th JECFA (2001). SYNONYMS α-schardinger dextrin,
More informationProject 5: Scoville Heat Value of Foods HPLC Analysis of Capsaicinoids
Willamette University Chemistry Department 2013 Project 5: HPLC Analysis of Capsaicinoids LABORATORY REPORT: Formal Writing Exercises PRE-LAB ASSIGNMENT Read the entire laboratory project and section 28C
More informationFast, Reproducible LC-MS/MS Analysis of Dextromethorphan and Dextrorphan
Fast, Reproducible LC-MS/MS Analysis of and Kimberly Phipps, Thermo Fisher Scientific, Runcorn, Cheshire, UK Application Note 685 Key Words Accucore C18, dextromethorphan, dextrorphan, SOLA CX Abstract
More informationORIENTAL JOURNAL OF CHEMISTRY An International Open Free Access, Peer Reviewed Research Journal. www.orientjchem.org
ORIENTAL JOURNAL OF CHEMISTRY An International Open Free Access, Peer Reviewed Research Journal www.orientjchem.org ISSN: 0970-020 X CODEN: OJCHEG 2014, Vol. 30, No. (1): Pg. 395-399 High Performance Thin
More informationGuide to Reverse Phase SpinColumns Chromatography for Sample Prep
Guide to Reverse Phase SpinColumns Chromatography for Sample Prep www.harvardapparatus.com Contents Introduction...2-3 Modes of Separation...4-6 Spin Column Efficiency...7-8 Fast Protein Analysis...9 Specifications...10
More informationCONFIRMATION OF ZOLPIDEM BY LIQUID CHROMATOGRAPHY MASS SPECTROMETRY
CONFIRMATION OF ZOLPIDEM BY LIQUID CHROMATOGRAPHY MASS SPECTROMETRY 9.1 POLICY This test method may be used to confirm the presence of zolpidem (ZOL), with diazepam-d 5 (DZP-d 5 ) internal standard, in
More informationDRAFT MONOGRAPH FOR THE INTERNATIONAL PHARMACOPOEIA PARACETAMOL ORAL SUSPENSION (September 2010)
September 2010 RESTRICTED DRAFT MONOGRAPH FOR THE INTERNATIONAL PHARMACOPOEIA PARACETAMOL ORAL SUSPENSION (September 2010) DRAFT FOR COMMENTS This document was provided by a quality control expert and
More informationMethod Development of LC-MS/MS Analysis of Aminoglycoside Drugs: Challenges and Solutions
Method Development of LC-MS/MS Analysis of Aminoglycoside Drugs: Challenges and Solutions authors Angela (Qi) Shen, Ling Morgan, Marcele L. Barroso, and Xin Zhang; Tandem Labs Tuyen Nguyen; Sepracor Inc.
More informationAnalytical Methods for Cleaning Validation
Available online at www.scholarsresearchlibrary.com Scholars Research Library Der Pharmacia Lettre, 2011, 3 (6): 232-239 (http://scholarsresearchlibrary.com/archive.html) ISSN 0975-5071 USA CODEN: DPLEB4
More informationAnalysis of Various Vitamins in Multivitamin Tablets
High Performance Liquid Chromatography Analysis of Various Vitamins in Multivitamin Tablets Effective August 24, 2007, the US Food and Drug Administration (FDA) issued a regulation (21 CFR Part 111) that
More informationReceived: 19 Jun2010, Revised and Accepted: 20 July 2010
International Journal of Pharmacy and Pharmaceutical Sciences ISSN- 0975-1491 Vol 2, Suppl 4, 2010 Research Article METHOD DEVELOPMENT AND VALIDATION FOR THE ESTIMATION OF OLOPATADINE IN BULK AND PHARMACEUTICAL
More informationScholars Research Library. A validated RP-HPLC method for estimation of Rivastigmine in pharmaceutical formulations
Available online at www.scholarsresearchlibrary.com Der Pharmacia Lettre, 2011, 3(3):421-426 (http://scholarsresearchlibrary.com/archive.html) ISSN 0975-5071 USA CODEN: DPLEB4 A validated RP-HPLC method
More informationAutomated Method Development Utilizing Software-Based Optimization and Direct Instrument Control
Automated Method Development Utilizing Software-Based Optimization and Direct Instrument Control Dr. Frank Steiner, 1 Andreas Brunner, 1 Fraser McLeod, 1 Dr. Sergey Galushko 2 1 Dionex Corporation, Germering,
More informationAll the prepared formulations were subjected for following. evaluation parameters and obtained results were showed in Tables 6.3 &
105 6.1 CHARACTERIZATION OF TABLETS All the prepared formulations were subjected for following evaluation parameters and obtained results were showed in Tables 6.3 & 6.4. 6.1.1 Description (Size, Shape,
More informationA commitment to quality and continuous improvement
Guidance for the Validation of Analytical Methodology and Calibration of Equipment used for Testing of Illicit Drugs in Seized Materials and Biological Specimens A commitment to quality and continuous
More informationExtraction of Epinephrine, Norepinephrine and Dopamine from Human Plasma Using EVOLUTE EXPRESS WCX Prior to LC-MS/MS Analysis
Application Note AN844 Extraction of, and from Human Plasma Using EVOLUTE EXPRESS WCX Page 1 Extraction of, and from Human Plasma Using EVOLUTE EXPRESS WCX Prior to LC-MS/MS Analysis Introduction Catecholamines
More information4.2 Bias, Standards and Standardization
4.2 Bias, Standards and Standardization bias and accuracy, estimation of bias origin of bias and the uncertainty in reference values quantifying by mass, chemical reactions, and physical methods standard
More informationOverview. Triple quadrupole (MS/MS) systems provide in comparison to single quadrupole (MS) systems: Introduction
Advantages of Using Triple Quadrupole over Single Quadrupole Mass Spectrometry to Quantify and Identify the Presence of Pesticides in Water and Soil Samples André Schreiber AB SCIEX Concord, Ontario (Canada)
More informationInternational GMP Requirements for Quality Control Laboratories and Recomendations for Implementation
International GMP Requirements for Quality Control Laboratories and Recomendations for Implementation Ludwig Huber, Ph.D. ludwig_huber@labcompliance.com Overview GMP requirements for Quality Control laboratories
More informationValidation and Calibration of Analytical Instruments a D.Gowrisankar, b K.Abbulu, c O.Bala Souri, K.Sujana*
Validation and Calibration of Analytical Instruments a D.Gowrisankar, b K.Abbulu, c O.Bala Souri, K.Sujana* a Department of Pharmaceutical Analysis, Andhra University, Visakhapatnam. b Department of Pharmaceutics,
More informationJournal of Chemical and Pharmaceutical Research, 2012, 4(6):3263-3274. Research Article
Available online www.jocpr.com Journal of Chemical and Pharmaceutical Research, 2012, 4(6):3263-3274 Research Article ISSN : 0975-7384 CODEN(USA) : JCPRC5 Impurities profiling Method and degradation studies
More informationHigh sensitivity assays using online SPE-LC-MS/MS -How low can you go? Mohammed Abrar Unilabs York Bioanalytical solutions, York, UK
High sensitivity assays using online SPE-LC-MS/MS -How low can you go? Mohammed Abrar Unilabs York Bioanalytical solutions, York, UK Background Unilabs YBS are a bioanalytical CRO based in York (Uk) Copenhagen
More informationTANNIC ACID. SYNONYMS Tannins (food grade), gallotannic acid, INS No. 181 DEFINITION DESCRIPTION
TANNIC ACID Prepared at the 39th JECFA (1992), published in FNP Add 1 (1992) superseding specifications prepared at the 35th JECFA (1989), published in FNP 49 (1990) and in FNP 52 (1992). Metals and arsenic
More informationß-CYCLODEXTRIN SYNONYMS
ß-CYCLODEXTRIN Prepared at the 44th JECFA (1995), published in FNP 52 Add 3 (1995) superseding specifications prepared at the 41st JECFA (1993), published in FNP 52 Add 2 (1993). Metals and arsenic specifications
More informationStandard Operating Procedure for Total Kjeldahl Nitrogen (Lachat Method)
Standard Operating Procedure for Total Kjeldahl Nitrogen (Lachat Method) Grace Analytical Lab 536 South Clark Street 10th Floor Chicago, IL 60605 April 15, 1994 Revision 2 Standard Operating Procedure
More informationHS 1003 Part 2 HS 1003 Heavy Metals Test
HS 1003 Heavy Metals Test 1. Purpose This test method is used to analyse the heavy metal content in an aliquot portion of stabilised hot acetic acid extract by Atomic Absorption Spectroscopy (AAS). Note:
More informationValidation and Calibration. Definitions and Terminology
Validation and Calibration Definitions and Terminology ACCEPTANCE CRITERIA: The specifications and acceptance/rejection criteria, such as acceptable quality level and unacceptable quality level, with an
More informationJennifer L. Simeone and Paul D. Rainville Waters Corporation, Milford, MA, USA A P P L I C AT ION B E N E F I T S INT RO DU C T ION
A Validated Liquid-Liquid Extraction Method with Direct Injection of Hexane for Clopidogrel in Human Plasma Using UltraPerformance Convergence Chromatography (UPC 2 ) and Xevo TQ-S Jennifer L. Simeone
More information1.1 This test method covers the qualitative and quantitative determination of the content of benzene and toluene in hydrocarbon wax.
Standard Method for Analysis of Benzene and Toluene Content in Hydrocarbon Waxes by Headspace Gas Chromatography EWF METHOD 002/03 (Version 1 Reviewed 2015) 1 Scope 1.1 This test method covers the qualitative
More informationChemistry 321, Experiment 8: Quantitation of caffeine from a beverage using gas chromatography
Chemistry 321, Experiment 8: Quantitation of caffeine from a beverage using gas chromatography INTRODUCTION The analysis of soft drinks for caffeine was able to be performed using UV-Vis. The complex sample
More information# LCMS-35 esquire series. Application of LC/APCI Ion Trap Tandem Mass Spectrometry for the Multiresidue Analysis of Pesticides in Water
Application Notes # LCMS-35 esquire series Application of LC/APCI Ion Trap Tandem Mass Spectrometry for the Multiresidue Analysis of Pesticides in Water An LC-APCI-MS/MS method using an ion trap system
More informationAssay Qualification Template for Host Cell Protein ELISA
Assay Qualification Template for Host Cell Protein ELISA Introduction: With ever increasing importance being placed on host cell protein (HCP) removal during the purification process, it is critical to
More informationVitamin C quantification using reversed-phase ion-pairing HPLC
Vitamin C quantification using reversed-phase ion-pairing HPLC Thomas Grindberg and Kristy Williams Department of Chemistry, Concordia College, 901 8 th St S, Moorhead, MN 56562 Abstract Vitamin C, an
More informationEXPERIMENT 11 UV/VIS Spectroscopy and Spectrophotometry: Spectrophotometric Analysis of Potassium Permanganate Solutions.
EXPERIMENT 11 UV/VIS Spectroscopy and Spectrophotometry: Spectrophotometric Analysis of Potassium Permanganate Solutions. Outcomes After completing this experiment, the student should be able to: 1. Prepare
More informationANALYTICAL METHOD DEVELOPMENT FOR DISSOLUTION RELEASE OF FINISHED SOLID ORAL DOSAGE FORMS
Academic Sciences International Journal of Current Pharmaceutical Research ISSN- 0975-7066 Vol 4, Issue 2, 2012 Research Article ANALYTICAL METHOD DEVELOPMENT FOR DISSOLUTION RELEASE OF FINISHED SOLID
More informationSession 3 Topics. Argatroban. Argatroban. Drug Use and Adverse Effects. Laboratory Monitoring of Anticoagulant Therapy
~~Marshfield Labs Presents~~ Laboratory Monitoring of Anticoagulant Therapy Session 3 of 4 Michael J. Sanfelippo, M.S. Technical Director, Coagulation Services Session 3 Topics Direct Thrombin Inhibitors:
More informationLab 2 Biochemistry. Learning Objectives. Introduction. Lipid Structure and Role in Food. The lab has the following learning objectives.
1 Lab 2 Biochemistry Learning Objectives The lab has the following learning objectives. Investigate the role of double bonding in fatty acids, through models. Developing a calibration curve for a Benedict
More informationDETERMINATION OF SALICYLAMIDE IN PHARMACEUTICAL TABLETS BY HIGH-PERFORMANCE THIN-LAYER CHROMATOGRAPHY WITH ULTRAVIOLET ABSORPTION DENSITOMETRY
ACTA CHROMATOGRAPHICA, NO. 16, 2006 DETERMINATION OF SALICYLAMIDE IN PHARMACEUTICAL TABLETS BY HIGH-PERFORMANCE THIN-LAYER CHROMATOGRAPHY WITH ULTRAVIOLET ABSORPTION DENSITOMETRY C. Sullivan and J. Sherma
More informationDevelopment and Validation of RP-HPLC Method for the determination of Methylphenidate Hydrochloride in API
International Journal of PharmTech Research CODEN (USA): IJPRIF ISSN : 0974-4304 Vol.6, No.2, pp 462-467, April-June 2014 Development and Validation of RP-HPLC Method for the determination of Methylphenidate
More informationUV Spectrophotometric estimation of Paracetamol and Lornoxicam in Bulk drug and Tablet dosage form using Multiwavelength
International Journal of PharmTech Research CODEN (USA): IJPRIF ISSN : 0974-4304 Vol.3, No.3, pp1603-1608, July-Sept 2011 UV Spectrophotometric estimation of Paracetamol and Lornoxicam in Bulk drug and
More informationAnalysis of Free Bromate Ions in Tap Water using an ACQUITY UPLC BEH Amide Column
Analysis of Free Bromate Ions in Tap Water using an ACQUITY UPLC BEH Amide Column Sachiki Shimizu, FUJIFILM Fine Chemicals Co., Ltd., Kanagawa, Japan Kenneth J. Fountain, Kevin Jenkins, and Yoko Tsuda,
More informationSPIKE RECOVERY AND DETERMINING A METHOD DETECTION LIMIT Pamela Doolittle, University of Wisconsin Madison, pssemrad@wisc.edu 2014
SPIKE RECOVERY AND DETERMINING A METHOD DETECTION LIMIT Pamela Doolittle, University of Wisconsin Madison, pssemrad@wisc.edu 2014 This experiment explores quality assurance practices which are commonly
More informationDrospirenone and Ethinyl Estradiol Tablets. Type of Posting. Revision Bulletin Posting Date. 31 July 2015 Official Date
Drospirenone and Ethinyl Estradiol Tablets Type of Posting Revision Bulletin Posting Date 31 July 2015 Official Date 01 August 2015 Expert Committee MonographsSmall Molecules 4 Reason for Revision Compliance
More informationORIGINAL SCIENTIFIC PAPER. Gabriella POHN. Éva VARGA-VISI SUMMARY KEY WORDS
ORIGINAL SCIENTIFIC PAPER 269 Determination of the Enantiomers of Methionine and Cyst(e)ine in the Form of Methionine-sulphon and Cysteic Acid After Performic Acid Oxidation by Reversed Phase High Performance
More information