Validated HPLC method for determination of carboxylic acid metabolite of clopidogrel in human plasma and its application to a pharmacokinetic study

Abstract

A new, simple, and reproducible method for determination of carboxylic acid metabolite of clopidogrel in human plasma has been developed. After liquid-liquid extraction in acidic medium with chloroform, samples were quantified on a Nova-pak C(8), 5 microm column using a mixture of 30 mM K(2)HPO(4)-THF-acetonitrile (pH = 3, 79:2:19, v/v/v) as mobile phase with UV detection at 220 nm. The flow rate was set at 0.9 mL/min. Ticlopidine was used as internal standard and the total run time of analysis was about 12 min. The method was linear over the range of 0.2-10 microg/mL of clopidogrel metabolite in plasma (r(2) > 0.999). The within-day and between-day precision values were in the range 1.0-4.8%. The limit of quantification of the method was 0.2 microg/mL. The method was successfully used to study the pharmacokinetics of clopidogrel in healthy volunteers.

Determination of clopidogrel in human plasma by liquid chromatography/tandem mass spectrometry: application to a clinical pharmacokinetic study

“…The inactive carboxylic acid metabolite is the most abundant species in plasma found at high concentrations (µg/mL levels). Pharmacokinetic studies of clopidogrel have been performed by measuring plasma levels of either the parent drug (Lainesse et al, 2004;Nirogi et al, 2006) or the carboxylic acid metabolite as an indirect approach (Lagorce et al, 1998;McEwen et al, 1999;Singh et al, 2005;Souri et al, 2006). Several assay methods are available for the determination of clopidogrel, including HPLC-UVD (Reist et al, 2000;Mitakos and Panderi, 2002), 14 C-labeling and radioactive counting (Lins et al, 1999), and LC/ MS/MS (Lainesse et al, 2004;Nirogi et al, 2006).…”

Pharmacokinetics of 600 mg loading dose of clopidogrel in patients undergoing percutaneous coronary intervention

“…Published pharmacokinetic parameters of clopidogrel administered at doses other than 600 mg were considered. Upon extrapolation to 600 mg dosing, there were similarities between C max and current study C max (Ksycinska et al, 2006;Souri et al, 2006;Bahrami et al, 2008).…”

“…Very few HPLC methods were reported for the determination of carboxylic acid metabolite of clopidogrel (Singh et al, 2005;Souri et al, 2006;Bahrami et al, 2008). HPLC is the most convenient and common analytical method for therapeutic drug monitoring, and it is readily available in majority of laboratories.…”

Clopidogrel: review of bioanalytical methods, pharmacokinetics/pharmacodynamics, and update on recent trends in drug–drug interaction studies

“…Initially, the easier strategy employed for the determination of clopidogrel was to merely measure the inactive moiety because it was found in abundance following in vivo dosing either in clinical samples (Lagorce et al, 1998;Souri et al, 2006) or in preclinical species (Singh et al, 2005). The measurement of the inactive carboxylic acid metabolite served the purpose of documenting the pharmacokinetic profile of clopidogrel in an indirect manner (Lagorce et al, 1998).…”