A novel RP-HPLC method for the simultaneous determination of R-warfarin (R-WAR), S-warfarin (S-WAR), aspirin (ASA) and its metabolite salicylic acid (SA) in beagle plasma was developed. Chromatographic separation was performed by a lux (R) cellulose-3 chiral column (250 mm x 4.6 mm, 5 mu m) equipped with a UV detector (288 nm), using the isocratic elution of 0.5 parts per thousand formic acid in methanol and isopropanol (90/10, v/v) at a flow-rate of 1.0 mL/min. Calibration plots were linear over range of 0.029-7.5 mu g/mL for (+/-)-WAR, 0.078-20 mu g/mL for ASA, and 0.195-100 mu g/mL for SA in beagle plasma. The validated method is successfully applied to a pharmacokinetic interaction study of WAR and ASA in beagles. The results show that coadministration of WAR with ASA may cause important pharmacokinetic interactions, which indicate that when WAR and ASA are administered together in clinical practice. Clinicians should pay more attention to bleeding risk and other safety-related issues.
[1]Anhui Med Univ, Dept Basic & Clin Pharmacol, Sch Pharm, Hefei 230032, Anhui, Peoples R China.
[2]Shanghai Univ Chinese Med, Ctr Drug Clin Res, Shanghai 20123, Peoples R China.
[3]Bengbu Med Coll, Dept Pharm, Bengbu 233030, Anhui, Peoples R China.
[4]Hefei Cosource Med Technol Co Ltd, Hefei 230031, Anhui, Peoples R China.
[5]Anhui Med Univ, Dept Endocrinol, Affiliated Hosp 1, Hefei 230022, Anhui, Peoples R China.
[6]Anhui Med Univ, Dept Cardiol, Affiliated Hosp 1, Hefei 230022, Anhui, Peoples R China.
(8.0+极速模式)