[Simultaneous determination of repaglinide and pravastatin sodium in rat plasma by LC-ms/MS and its application on pharmacokinetic interactions study].
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 repaglinide increased significantly (P<0.05) and tmax of pravastatin sodium prolonged (P<0.05) in co-administration group. The method is found to be simple, sensitive and accurate for determining the concentration of repaglinide and pravastatin sodium in rat plasma. There exists pharmacokinetic interactions in the co-administration of repaglinide and pravastatin sodium.
Yan-Rong
YR
Ma
Yan
Y
Zhou
Guo-Qiang
GQ
Zhang
Zhi
Z
Rao
Jing
J
Huang
Yu-hui
YH
Wei
Xin-An
XA
Wu
D000284:Administration, Oral; D000818:Animals; D002219:Carbamates / Q000008:administration & dosage / Q000097:blood* / Q000493:pharmacokinetics; D002851:Chromatography, High Pressure Liquid; D004347:Drug Interactions; D008297:Male; D010880:Piperidines / Q000008:administration & dosage / Q000097:blood* / Q000493:pharmacokinetics; D017035:Pravastatin / Q000008:administration & dosage / Q000097:blood* / Q000493:pharmacokinetics; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D021241:Spectrometry, Mass, Electrospray Ionization; D053719:Tandem Mass Spectrometry
D002219:Carbamates; D010880:Piperidines; C072379:repaglinide; D017035:Pravastatin