Determination of glibenclamide in human plasma by LC-MS and study of its pharmacokinetics in healthy Chinese volunteers

Aim: To determine the concentration of glibenclamide in human plasma and investigate its pharmacokinetics in Chinese male volunteers following oral administration of a single dose of 5 mg. Method: Plasma samples were processed by liquid-liquid extraction and a high-performance liquid chromatographic-electrospray ionization mass spectroscopy (HPLC-ESI-MS) for determination of intact glibenclamide in human plasma has been developed. Result: The method was linear in the 1.56 ∼ 400 ng/ml concentration range (r = 0.9999). The recovery of glibenclamide was more than 80%. Within-day and between-day precision, expressed as the relative standard deviation (RSD), ranged from 3.6% to 6.8% and 6.1% to 8.4% respectively. The sensitivity of the method was 0.5 ng/ml. The assay was used to estimate the pharmacokinetics of glibenclamide after oral administration of a 5 mg tablet of glibenclamide to 18 healthy volunteers. Its main pharmacokinetic parameters were: AUC_0-∞ = (813.6 ± 254.2) μg·h/L, AUC_0-t = (790.6 ± 248.2) μg·h/L, c_max = (130.1 ± 64.8) ng/ml, t_max = (2.6 ± 1.8) h and t_1/2 = (2.7 ± 1.9) h. Conclusion: The method described in this report has high sensitivity and selectivity for accurate determination of the human plasma concentration of glibenclamide.