Simultaneous determination of repaglinide and pravastatin sodium in rat plasma by LC-ms/MS and its application on pharmacokinetic interactions study

• Published in: Yao hsüeh hsüeh pao Vol. 49; no. 1; p. 72
• Main Authors: Ma, Yan-Rong, Zhou, Yan, Zhang, Guo-Qiang, Rao, Zhi, Huang, Jing, Wei, Yu-hui, Wu, Xin-An
• Format: Journal Article
• Language: Chinese
• Published: China 01.01.2014
• Subjects: Administration, Oral; Animals; Carbamates - administration & dosage; Carbamates - blood; Carbamates - pharmacokinetics; Chromatography, High Pressure Liquid; Drug Interactions; Male; Piperidines - administration & dosage; Piperidines - blood; Piperidines - pharmacokinetics; Pravastatin - administration & dosage; Pravastatin - blood; Pravastatin - pharmacokinetics; Random Allocation; Rats; Rats, Sprague-Dawley; Reproducibility of Results; Sensitivity and Specificity; Spectrometry, Mass, Electrospray Ionization; Tandem Mass Spectrometry
• ISSN: 0513-4870

The study aims to establish a method for simultaneous determination of repaglinide and pravastatin sodium in rat plasma by LC-MS/MS and to study its pharmacokinetic interactions. Eighteen male SD rats were divided into repaglinide group, pravastatin sodium group and co-administration group. Blood samples were collected at different times after oral administration. Repaglinide and pravastatin sodium in rat plasma were separated by Agilent HC-C18 with the mobile phase consisting of methanol-0.1% formic acid (80 : 20). Detection and quantification were performed by using ESI-MS. The detector was operated in selected Reaction-monitoring mode at m/z 453.3-->230.1 for repaglinide, m/z 447.2-->327.4 for pravastatin sodium and m/z 285.1-->192.9 for diazepam as the internal standard. The calibration curve obtained was linear (R2>0.99) over the concentration range of 9.77-10,000 ng.mL-1 for repaglinide and 4.88-625 ng.mL-1 for pravastatin sodium. Compared with the single administration group, Cmax and AUC0-6h of repagl