Determination of Nateglinide in Human Plasma by LC-ESI-MS and Its Application to Bioequivalence Study

To evaluate the bioequivalence of nateglinide, a rapid and specific liquid chromatographic-electrospray ionization mass spectrometric method was developed and validated to determine nateglinide for human plasma samples. The analyte was detected using electrospray positive ionization mass spectrometry in the selected ion monitoring mode. Tinidazole was used as the internal standard. A good linear relationship obtained in the concentration ranged from 0.05 to 16 mu g mL(-1) (r (2) = 0.9993). Lower limit of quantification was 0.05 mu g mL(-1) using 100 mu L of plasma sample. Intra- and inter-day relative standard deviations were 2.1-7.5 and 4.7-8.9%, respectively. Among the pharmacokinetic data obtained, T (max) was 2.09 +/- A 1.06 h for reference formulation and 2.40 +/- A 0.97 h for test formulation. C (max) was 4.17 +/- A 1.31 mu g mL(-1) for reference formulation and 4.37 +/- A 1.53 mu g mL(-1) for test formulation. The half-life (t (A1/2)) was 1.93 +/- A 0.44 h for reference formulation and 1.92 +/- A 0.29 h for test formulation. AUC(0-10h) was 13.67 +/- A 4.36 mu g h mL(-1) for reference formulation and 13.21 +/- A 4.09 mu g h mL(-1) for test formulation. This method was successfully applied to the pharmacokinetic study in human plasma samples.