Bioequivalence Assessment of Fluconazole Capsules in Human Plasma by HPLC-MS Article Abstract
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Published: March 28, 2006
Objective: To establish a HPLC-MS method for rapid determination of fluconazole in human plasma and to assess the pharmacokinetics and bioequivalence of fluconazole capsules in healthy volunteers. Methods: After being deproteined by methanol, plasma samples were separated by HPLC on a reversed-phase lichrospher C_ 18 column (250 mm×4.6 mm,5 μm) with a mobile phase of methanol-water (65∶35, containing 0.05% formic acid and 40 mol/L ammonium acetate) at a flow rate of 0.8 mL/min and metronidazole was used as internal standard. HPLC-MS was performed in the selected ion monitoring (SIM) mode using target ions, + (m/z: 307.2) for fluconazole and + (m/z: 172.3) for the internal standard, and fragment voltage of 70 V. A randomized crossover trial was performed in 20 healthy volunteers, who took a single 150 mg dose of test capsules or reference capsules respectively, followed by periodically determining fluconazole in human plasma. Results: The standard curves were linear in the range of 30.69 μg/L～20.46 mg/L (r=0.9998, n=5) and the low limit of detection for fluconazole was about 10 μg/L. The RSDs of intra-and inter-day were all less than 10% and the extraction recovery rates were more than 90% for all test concentrations of samples. The relative bioavailability of test capsules was (106.4±11.8)% and the two preparations were bioequivalent. Conclusion: The assay is proved to be rapid, sensitive, accurate, convenient and specific, and is suitable for the determination of fluconazole in human plasma and pharmacokinetic study.