Determination of the Concentrations of Butyric Acid Clevidipine in Beagle Dogs Plasma by LC-MS/MS

Pharmacokinetic parameters of the cleviprex fat emulsion injection and original research products in beagle dogs plasma were identified by liquid chromatography-tandem mass spectrometry (LC-MS/MS). Taking amlodipine as internal standard, metabolites were separated on Phenomenex Luna C8（2.0 mm×150 mm×5 μm） column by the gradient elution with methanol 0.1% formic acid (82∶18, V/V) as mobile phase, and detected by positive ions electrospray ionization (ESI) mass spectrometry with fullscan-data dependent scan. Data was disposed through MassLynx4.1. The result shows that the linear range of cleviprex is 0.4-100 μg/L. The average values of C_max, T_max, T_1/2, AUC_0→t and AUC_0→∞ are (58.748±16.738) μg/L, (2.938±0.678) μg/L, (11.88±3.824) min, (1 883.821±647.882) μg•min/L, (1889.834±649.135) μg•min/L for the reference preparation, respectively. While the average values of C_max, T_max, T_1/2, AUC_0→t and AUC_0→∞ are (53.706±18.963) μg/L, (2.875±0.991) μg/L, (11.587±3.634) min, (1 856.541±590.653) μg•min/L, (1 863.485±592.039) μg•min/L, for the test preparation, respectively. ANOVA and two one sided t tests analysis show that there is no significant difference with the pharmacokinetic parameters of the two formulations, and they have bioequivalent in Beagle dogs plasma.