Abstract:

Aim To develop a liquid chromatographic-tandem mass spectrometric (LC-MS-MS) method to determine clarithromycin in human plasma. Methods The analyte and internal standard roxithromycin were extracted from plasma samples by n-nexane-dichloromethane-isopropanol (300:150:15, V/V/V) and chromatographed on a C18 column. The mobile phase consisted of methanol-water-formic acid (80:20:1, V/V/V). Detection was performed on a triple quadrupole tandem mass spectrometer via electrospray ionization source (ESI) in the positive mode. Results The method had a lower (limit) of quantification of 10.0 ng·mL^-1 when 0.2 mL plasma was used. The linear calibration curves were obtained in the concentration range of 10.0-5000 ng·mL^-1. The intra- and inter-run precisions were lower than 3.3% in terms of relative standard deviation (RSD), and the accuracy ranged ±0.7% in terms of relative error (RE). Tmax, Cmax, T1/2 and AUC0-24h values were found to be (3.1±2.7)h, (8750±4734)ng·mL^-1, (5.3±2.2) h, and (5 932±2 449)ng·mL^-1, respectively, after a single oral dose of 250 mg clarithromycin tablet to 18 volunteers. Conclusion This validated method was successful in the evaluation of pharmacokinetic profiles of clarithromycin tablets administered to 18 healthy male volunteers.

Key words: clarithromycin, clarithromycin, LC-MS-MS, LC-MS-MS, pharmacokinetics, pharmacokinetics