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Journal of Analytical Methods in Chemistry
Volume 2015 (2015), Article ID 892470, 12 pages
http://dx.doi.org/10.1155/2015/892470
Research Article

Development and Validation of an HPLC Method for Simultaneous Quantification of Clopidogrel Bisulfate, Its Carboxylic Acid Metabolite, and Atorvastatin in Human Plasma: Application to a Pharmacokinetic Study

1Faculty of Pharmacy, Department I of Pharmacy, University of Medicine and Pharmacy, Petru Rares Street, 200349 Craiova, Romania
2Faculty of Pharmacy, Doctoral School, University of Medicine and Pharmacy, Petru Rares Street, 200349 Craiova, Romania
3Faculty of Pharmacy, Department II of Pharmacy, University of Medicine and Pharmacy, Petru Rares Street, 200349 Craiova, Romania

Received 19 September 2015; Revised 23 November 2015; Accepted 30 November 2015

Academic Editor: Bengi Uslu

Copyright © 2015 Octavian Croitoru et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Supplementary Material

The supplementary data contains chromatograms of plasma spiked with respective standards of clopidogrel bisulfate, its carboxylic acid metabolite, atorvastatin and ibuprofen (IS.) at 50 μg·mL-1, obtained under the optimized chromatographic method. The chromatograms are presented in Figure S1 in order to detect any peaks interfering the target compounds. The chromatograms indicate no significant interference from impurities at the retention times of the analytes ( tR=9.64 min for clopidogrel carboxylic acid metabolite, 10.94 min for atorvastatin, 12.50 min for clopidogrel bisulfate and 11.90 min for ibuprofen as IS). Linearity of the calibration curves was estimated for the ratio of the peak area of clopidogrel bisulfate, its carboxylic acid metabolite and atorvastatin to that of the internal standard, ibuprofen (Figure S2), covering the range of 0.008-2 μg·mL-1 for clopidogrel bisulfate, 0.01-4 μg·mL-1 for its carboxylic acid metabolite and 0.005-2.5 μg·mL-1 for atorvastatin. The equations of calibration curves presented in Table S1 were used to calculate concentrations of clopidogrel bisulfate, its carboxylic acid metabolite and atorvastatin in patients´ plasma. The correlation coefficients were also calculated and presented in Table S1.

Data from seven sampling times within 12 h after multiple oral drug intakes were used to calculate pharmacokinetic parameters: absorption rate constant, ka, time of peak concentration, tmax, maximum plasma concentration, Cmax, eliminate rate constant, ke, Area under the concentration-time curve from time zero to time t (AUC0-t) and Area under the concentration-time curve from time zero to time infinity (AUC0-∞).

The plasma levels of the analytes were used to calculate pharmacokinetic parameters by mathematical calculations. Cmax and tmax were read from individual analyte concentration-time curve. The elimination half-life( t1/2) was estimated from ln2/ke, where ke is the elimination rate constant. Area under the concentration-time curve from time zero to time t (AUC0-t), where t is the last measurable time, was calculated by trapezoidal rule. The total area under the concentration-time curve (AUC0-∞).was estimated by trapezoidal rule with extrapolation to infinity using Ct/ke

  1. Supplementary Material