Pharmacokinetic study of talipexole hydrochloride in combination with madopar in human plasma by LC-MS/MS

OBJECTIVE: To develop a sensitive LC-MS/MS method for pharmacokinetic study of talipexole hydrochloride in combination with madopar in human plasma. METHODS: Clenbuterol hydrochloride was used as internal standard (IS). Liquid-liquid extraction with ethyl acetate was used for sample preparation. Chromatographic separation was carried on a Lichrospher C6H 6 column with MS/MS detection by using positive electrospray ionization and selective reaction monitoring. A single oral dose of 0.4 mg talipexole hydrochloride tablets or talipexole in combination with 0. 25 g madopar were given to 12 healthy volunteers in this open-label, randomized, crossover study. RESULTS: The calibration curve was linear within the range of 0.10-10.0 μg·L-1, the method recovery was 80.8%-86.2%, RSDs of intra-day and inter-day were 0.5%-4.8% and 2.4%-8.6%, respectively. ρmax, tmax, t1/2, MRT, AUC0-36, AUC0-∞, CL/F and Vd/F of talipexole hydrochloride after a single oral dose of 0.4 mg talipexole hydrochloride tablets and talipexole in combination with 0.25 g madopar were (0.96 ± 0.12) and (0.89 ± 0.16) μg·L-1, (1.4 ± 0.9) and (1.4 ± 0.9) h, (11.37 ± 1.99) and (11.61 ± 1.80) h, (15.90 ± 2.95) and (16.35 ± 2.60) h, (9.66 ± 1.33) and (9.36 ± 1.58) μg·h·L-1, (11.07 ± 1.72) and (10.82 ± 1.98) μg·h·L-1, (37.9 ± 7.50) and (40.5 ± 10.0) L·h-1, (650 ± 186) and (601 ± 167) L, respectively. There were no significant differences between two administrations assessed by One-way ANOVA and independent-samples t test. CONCLUSION: The LC-MS/MS method was sensitive and selective with no endogenous interferences. The plasma pharmacokinetics of talipexole hydrochloride was not affected by the co-administration of madopar.