Pharmacokinetics and Determination of Fluconazole in Human Plasma by LC-MS/MS

A LC-MS/MS method was established for the determination of fluconazole(1) in human plasma.A C_(18) column was used with phentolamine mesylate(2) as the internal standard and 2 mmol/L ammonium acetate solution (containing 0.05%formic acid)-methanol(40:60) as the mobile phase.ESI was applied and operated in positive ion multiple-reaction monitoring mode.The detected ions were m/z 307.2→238.2(1) and m/z 282.2→212.2(2).The calibration curve was linear in the concentration range of 0.03 - 10μg/ml.The recovery was over 94%and the extraction recovery was above 90%.The inter- and intra-day RSDs were less than 5.4%.A single oral dose of 150 mg 1 tablets were given to 20 male healthy volunteers.The main pharmacokinetic parameters were as follows:c_(max)(3.26±0.54)μg/ml, t_(max)(1.42±0.65) h,t_(1/2)(29.75±4.89) h,AUC_(0→120h)(131.4±23.4)μg·ml~(-1)·h and AUC_(0→∞)(140.5±26.3)μg·ml~(-1)·h.