RP-UFLC METHOD DEVELOPMENT AND VALIDATION FOR SIMULTANEOUS ESTIMATION OF CLOPIDOGREL, PANTOPRAZOLE AND ROSUVASTATIN IN HUMAN PLASMA: DRUG INTERACTION STUDIES
Keywords:
Bioanalytical, Clopidogrel, Pantoprazole & Rosuvastatin, RP-UFLC, USFDAAbstract
Objectives: Objective of our present study was to develop a novel ultra fast liquid chromatographic method for quantitative simultaneous estimation of Clopidogrel, Pantoprazole & Rosuvastatin in human plasma and to validate the developed method following USFDA guidelines.
Methods: In the current study, the analysis was performed on phenomenex C8 (250 × 4.6 mm, 5μm) column using phosphate buffer (pH-2.5) and acetonitrile (45: 55 v/v) as mobile phase at flow rate of 1.2 mL/min. The system consisted of a pump (Shimadzu, prominence, UFLC), with 20 µl sample injector, along with a PDA detector at a wavelength of 254, 243 nm and 220 nm for Clopidogrel, Pantoprazole and Rosuvastatin respectively. Data was compiled using Shimadzu LC Solution software.
Results: In this developed method Clopidogrel, Pantoprazole & Rosuvastatin, eluted at a retention time of 2.566, 5.002 and 9.301 min respectively. The proposed method is having linearity in the concentration range from 5 to 50μg/mL of Clopidogrel, Pantoprazole & Rosuvastatin. The current method was validated with respect to accuracy, linearity; precision, lowest limit of quantification (LLOQ) and recovery according to the USFDA guidelines.  A good linear relationship over the concentration range of 5-50µg/ml was shown. Validation of the method was carried out as per the USFDA draft guidelines.
Conclusion: A novel specific, accurate, precise UFLC method was developed for quantitative simultaneous estimation of Clopidogrel, Pantoprazole & Rosuvastatin in human plasma and validated. The developed method is suitable and economic for routine analysis and pharmacokinetic studies of Clopidogrel, Pantoprazole & Rosuvastatin simultaneously. The method developed was found to be precise, accurate, specific, linear and sensitive. Statistical analysis shows that the method is reproducible and selective for the estimation of Clopidogrel, Pantoprazole & Rosuvastatin in dosage form of patient plasma.
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Douglas IJ, Evans SJW, Hingorani AD, Grosso AM, Timmis A, Hemingway H, et al. Clopidogrel and interaction with proton pump inhibitors: comparison between cohort and within person study designs. Bio Med J 2012;345-59.
Duke JD, Han X, Wang Z, Subhadarshini A, Karnik SD, Li X, Hall SD, et al. Literature based drug interaction prediction with clinical assessment using electronic medical records: novel myopathy associated drug interactions. PLoS Comput Biol 2012;8(8):2614-27.
Azcona L, Lopez Farre AJ, Mateos Caceres PJ, Segura A, Rodriguez P, Modrego J, et al. Impact of clopidogrel and aspirin treatment on the expression of proteins in platelets from type-2 diabetic patients with stable coronary ischemia. J Pharm Sci 2012;101:2821–32.
Evans AM. Enantio selective pharmacodynamics and pharmacokinetics of chiral nonsteroidal anti-inflammatory drugs. Eur j Clin Pharmacol 1992;42(3):237-56.
Brooks PM, Day RO. Non steroidal anti inflammatory drugs—differences and similarities. N Engl J Med 1991;324(24):1716-25.
Mills RFN, Adams SS, Cliffe EE, Dickinson W, Nicholson JS. The metabolism of ibuprofen. Xenobiotica 1973;3(9):589-98.
Brune K. Comparative pharmacology of non-opoid analgesics. Med Toxocol 1986;1 Suppl 1:1-9.
Guidance for Industry, Bioanalytical Method Validation 2001:1-20.
Silverstein RM, Bassler GC, Morrill TC. Spectrometric identification of organic compounds. 5th ed. New York: J Wiley Son Inc; 1991:117-23.
Reddy RS, Chandiran IS, Jayaveera KN, Divi KR. Quantification of ibuprofen in human plasma using high throughput liquid chromatography-tandem mass spectrometric method and its applications in pharmacokinetics. Scholar Res Library 2010;2(3):101-11.
ICH guidelines. Text on Validation of Analytical Procedures-Methodology (ICH Q2A);1996.
Becker LB, Kallewaard M, Caspers PW, Visser LE, Leufkens HG. Hospitalizations and emergency department visits due to drug–drug interactions: a literature review. Pharmacoepidemiol Drug Saf 2007;16:641-51.
Juurlink DN, Mamdani M, Kopp A, Laupacis A, Redelmeier DA. Drug-Drug interactions among elderly patients hospitalized for drug toxicity. JAMA 2003;289:1652-8.
Jankel CA, Fitterman LK. Epidemiology of drug-drug interactions as a cause of hospital admissions. Drug Saf 1993;9:51-9.
Leape LL, Bates DW, Cullen DJ, Cooper J, Demonaco HJ. Systems analysis of adverse drug events. JAMA 1995;274:35-43.
Sridhar J, Liu J, Foroozesh M, Cheryl L. Klein Stevens Insights on Cytochrome P450 Enzymes and Inhibitors Obtained Through QSAR Studies. NIH Public Access 2013;17(8):9283-305.
Wolf CR, Smith G, Smith RL. Science, medicine and the future pharmacogenetics. Br Med J 2000;320:987-90.
Arimoto R. Computational models for predicting interaction with cytochrome P450 enzyme. Curr Top Med Chem 2006;6:1909-18.
Ogu C, Maxa J L. Drug interactions due to cytochrome P450. BUMC PROCEEDINGS 2000;13:421-23.
Zakia Bibi. Role of cytochrome P450 in drug interactions. Nutrition Metabolism 2008;5(27):1743-52.
Ogawa R, Echizen H. Drug-Drug interaction profiles of proton pump inhibitors. Clin Pharmacokinet 2010;49(8):509-33.
Lima JP, Brophy JM. The potential interaction between clopidogrel and proton pump inhibitors: a systematic review. BMC Medicine 2010;8(6):80-1.
Kwan J, Htun WW, Huang Y, Ko W, Kwan TW. Effect of proton pump inhibitors on platelet inhibition activity of clopidogrel in Chinese patients with percutaneous coronary intervention. Vasc Health Risk Manage 2011;7:399-404.
Kim GB, Kim JK, Park S, Jeong JJ, Yoon HS, Ko SH, et al. Effect of atorvastatin and clopidogrel co-administration after coronary stenting in korean patients with stable angina. Korean Society Cardiology 2011;41(1):24-8.
Drepper MD, Spahr L, Frossard JL. Clopidogrel and proton pump inhibitors-where do we stand in 2012? World J Gastroenterol 2012;18(18):2161-71.
Schmidt M, Johansen M, Maeng M, Kaltoft A, Jensen LO, Tilsted HH, et al. Concomitant use of clopidogrel and statins and risk of major adverse cardiovascular events following coronary stent implantation. Br J Clin Pharmacol 2012;74(1):161-70.
Juurlink DN, Gomes T, Ko DT, Szmitko PE, Austin PC, Tu JV, Henry DA, et al. A population-based study of the drug interaction between proton pump inhibitors and clopidogrel. Canadian Med Assoc J 2009;180(7):713-8.
Li W, Zeng S, Yu LS, Zhou Q. Pharmacokinetic drug interaction profile of omeprazole with adverse consequences and clinical risk management. Ther Clin Risk Manage 2013;9:259-71.
Sepehri G, Khazaelli P, Dahooie FA, Sepehri E, Dehghani MR. Prevalence of potential drug interactions in an iranian general hospital. Indian J Pharm Sci 2012;74(1):75-9.
Konda RK, Challa BR., Chandu BR, Chandrasekhar KB. Bioanalytical method development and validation of memantine in human plasma by high performance liquid chromatography with tandem mass spectrometry: application to bioequivalence study. J Anal Methods Chem 2012;2012:1155-62.
Mishra NK, Agarwal S, Raghava GPS. Prediction of cytochrome P450 isoform responsible for metabolizing a drug molecule. BMC Pharmacology 2010;10(8): 1471-80.
Vijayaraghavan R, Jayababu G, Prasad R, Thirugnanam P, Shivkumar G, Sriraam VT, et al. Bio-Analytical method development and validation for Omeprazole using LC-MS/MS. Indian J Pharm Sci Res 2011;2(9):2475-81.
Patel VK, Acharya LD, Rajakannan T, Surulivelrajan M, Guddattu M, Padmakumar R. Potential drug interactions in patients admitted to cardiology wards of a south Indian teaching hospital. Australasian Medical J 2011;4(1):9-14.
Samer CF, Lorenzini KI, Rollason V, Daali Y, Desmeules JA. Applications of CYP450 testing in the clinical setting. Mol Diagn Ther 2013;17:165–84.
Tripathi KD. Essentials of Medical Pharmacology. 5th ed. New Delhi: Jaypee Brothers; 2003:167-84, 245-8.
FDA Guidance for Industry, Bioanalytical Method Validation, Biopharmaceutics, September; 2013.