PHARMACOKINETIC PROFILE OF 75 MG CLOPIDOGREL IN PLASMA OF INDONESIAN HEALTHY SUBJECTS BY ULTRA HIGH-PERFORMANCE LIQUID CHROMATOGRAPHY-TANDEM MASS SPECTROMETRY
Keywords:Clopidogrel, Ultra-high-performance liquid chromatography-tandem mass spectrometry, Plasma, Pharmacokinetic profile, Bioanalysis
Objective: This study aimed to determine clopidogrel in plasma to obtain its pharmacokinetic profile using ultra-high-performance liquid
chromatography-tandem mass spectrometry (UPLC-MS/MS).
Methods: Clopidogrel analysis was performed in vivo by UPLC-MS/MS using validated methods. Subjects received 75 mg clopidogrel, and plasma
samples were collected at 14 time points after 0 baseline (pre-dose): 0.25, 0.5, 0.75, 1, 1.25, 1.5, 2, 3, 4, 8, 12, 18, and 24 h.
Results: A linear calibration curve was produced in the range of 20â€“5.000 pg/mL. This method fulfills the criteria for validation according to the
European Medicines Agency guidelines. The obtained pharmacokinetic profile of clopidogrel was as follows: Maximum concentration=1.146 ng/mL,
time at maximum concentration (tmax)=1 h, half-life (tÂ½)=7.01 h, area under curve (AUC)0âˆ’t=7.420 ng h/mL, and AUC0âˆ’t=8.111 ng h/mL.
Conclusion: Clopidogrel analysis using a UPLC/MS-MS system with liquid-liquid extraction method was successfully conducted using plasma samples
from three healthy subjects who administered 75 mg of clopidogrel tablet.
European Medicines Agency. Assessment Report for Clopidogrel Teva.
London: European Medicines Agency; 2009.
Indonesia National Agency of Food and Drug Control. Regulation
from Head of Indonesia National Agency of Food and Drug Control
No. HK.03.1.23.12.11.10217 about Drugs Obligate Equivalence Test.
Jakarta; 2011. [In Indonesian]
Alesci J, Victorino A. Clopidogrel. New York: Nova Biomedical/Nova
Bhargav K, Venkata SB, Venkata SK, Himaja G, Samuel GG,
Bhaskar RK. Pharmacokinetic drug interaction between clopidogrel
and esomeprazole in adult healthy male volunteers. Asian J Pharm Clin
Gurupadayya BM, Sama S. Bio-analytical determination of clopidogrel
and pantoprazole by RP-HPLC method in rat plasma: Application to
drug interaction study. Asian J Pharm Clin Res 2014;7:10-3.
Reddy DN. Design, development and characterization of clopidogrel
bisulfate transdermal drug delivery system. Asian J Pharm Clin Res
Harahap Y. Role of Bioanalysis in Assuring Drug Quality and Increasing
Quality of Patient Life. Depok: UI Press; 2010.
KarazÌniewicz-Åada M, Danielak D, TezÌ‡yk A, ZÌ‡aba C, Tuffal G,
GÅ‚Ã³wka F. HPLCâ€“MS/MS method for the simultaneous determination
of clopidogrel, its carboxylic acid metabolite and derivatized isomers of
thiol metabolite in clinical samples. J Chromatogr B 2012;911:105-12.
Divi KR, Jayaveera KN, Naidu YK, Reddy MK. Development and
validation of high-throughput liquid chromatographyâ€“tandem mass
spectrometric method for simultaneous quantification of clopidogrel
and its metabolite in human plasma. J Chromatogr B 2010;878:502-8.
Zou JJ, Tan J, Fan HW, Chen SL. Bioequivalence study of clopidogrel
mg tablets in healthy male volunteers. J Bioequiv Bioavailab
European Medicines Agency. Guideline on Bioanalytical Method
Validation. London: European Medicines Agency; 2011.
Robinson A, Hillis J, Neal C, Leary AC. The validation of a
bioanalytical method for the determination of clopidogrel in human
plasma. J Chromatogr B 2007;848:344-54.