High Performance Liquid Chromatographic Determination ofInactive Carboxylic Acid Metabolite of Clopidogrel in HumanSerum: Application to a Bioequivalence Study
Iranian Journal of Pharmaceutical Sciences,
Vol. 5 No. 4 (2009),
1 Mehr 2009
,
Page 231-238
https://doi.org/10.22037/ijps.v5.41228
Abstract
A sensitive and rapid method is described for determination of clopidogrel carboxylic acid (CCA), the inactive metabolite of the antiplatelet agent clopidogrel in human serum. The analytical procedure involves liquid-liquid extraction of the analyte and an internal standard (phenytoin) with ethyl acetate. Amobile phase consisting of 0.05 M phosphate buffer containing triethylamine (0.5 ml/l; pH 5.7)and acetonitrile (56:44; v/v) was used and chromatographic separation was achieved using a C18analytical column at detector wavelength of 220 nm. The calibration curves were linear over a concentration range of 0.05-10 μg/ml of CCAin human serum. The total run time of analysis was 5.5 min. and the lower limits of detection (LOD) and quantification (LOQ) were 0.02 and 0.05 μg/ml, respectively. The method validation was carried out in terms of specificity, sensitivity, linearity,precision, accuracy and stability. The validated method was applied in a randomized cross-over bioequivalence study of two different clopidogrel preparations in 24 healthy volunteers.
- Bioequivalence study
- Clopidogrel
- HPLC
- Metabolites.
How to Cite
References
[2]Herbert JM, Frehel D, Vallee E, Kieffer G, Gouy D, Berger Y, Defreyn G, Maffrand JP. Clopidogrel,a novel antiplatelet and antithrombotic agent.Cardiovascular Drug Rev1993; 2: 180-98.
[3]Lagorce P, Perez Y, Ortiz J, Necciari J, Bressolle F. Assay method for the carboxylic acid metabolite of clopidogrel in human plasma by gas chromatography-mass spectrometry. J Chromatogr B1998; 720: 107-17. [4]Ksycinska H, Rudzki P, Kiliszek MB.Determination of clopidogrel metabolite (SR26334) in human plasma by LC-MS. J Pharm Biomed Anal2006; 41: 533-9.
[5]Mitakos A, Panderi I. Determination of the carboxylic acid metabolite of clopidogrel in human plasma by liquid chromatography-electrospray ionization mass spectrometry. Anal Chim Acta 2004; 505:107-14.[6]Singh SS, Sharma K, Barot D, Mohan PR, Lohray VB. Estimation of carboxylic acid metabolite of clopidogrel in Wistar rat plasma by HPLC and its application to a pharmacokinetic study. JChromatogr B2005; 821: 173-80.
[7]Souri E, Jalalizadeh H, Kebriaee-Zadeh A,Shekarchi M, Dalvandi A. Validated HPLC method for determination of carboxylic acid metabolite of clopidogrel in human plasma and its application to a pharmacokinetic study. Biomed Chromatogr 2006; 20: 1309-14.
[8]Caplain H, Francois MD, Gaud C, Necciari J.Pharmacokinetics of clopidogrel. Semin Thromb Hemost1999; 25: 25-8.
[9]Shin BS, Yoo SD. Determination of clopidogrel in human plasma by liquid chromatography/tandem mass spectrometry: Application to a clinical pharmacokinetic study. Biomed Chromatogr 2007; 21: 883-9.
- Abstract Viewed: 274 times
- IJPS_Volume 5_Issue 4_Pages 231-238 Downloaded: 266 times