Development and validation of a liquid chromatography-tandem mass spectrometry assay for the simultaneous quantitation of prednisolone and dipyridamole in human plasma and its application in a pharmacokinetic study.
We have developed and validated an accurate, sensitive, and robust LC-MS/MS method that determines the concentration of CRx-102 (the combination of prednisolone and dipyridamole) in human plasma. In this method, prednisolone, dipyridamole, and the combined internal standards (IS) prednisolone-d(6) (IS for prednisolone) and dipyridamole-d(20) (IS for dipyridamole) were extracted from 100 microL human EDTA plasma using methylbutyl ether. Calibration curves were linear over a concentration range of 0.4-200 ng/mL for prednisolone and 5-3000 ng/mL for dipyridamole. The analytes were quantitatively determined using tandem mass spectrometry operated in positive electrospray ionization in a multiple reaction monitoring (MRM) mode. This validated method has been used successfully in clinical pharmacokinetic studies of CRx-102 in healthy volunteers.
Chen
Mei
M
Department of Preclinical Development and Formulations, CombinatoRx, Inc., Cambridge, MA 02142, USA.
Granvil
Camille
C
Ji
Qin C
QC
Zhang
Zhi-Yi
ZY
Padval
Mahesh V
MV
Kansra
Vikram V
VV
D019540:Area Under Curve; D002138:Calibration; D002853:Chromatography, Liquid / Q000379:methods*; D004176:Dipyridamole / Q000097:blood* / Q000737:chemistry / Q000493:pharmacokinetics; D004338:Drug Combinations; D004355:Drug Stability; D005615:Freezing; D006207:Half-Life; D006801:Humans; D008657:Metabolic Clearance Rate; D015394:Molecular Structure; D011239:Prednisolone / Q000097:blood* / Q000737:chemistry / Q000493:pharmacokinetics; D011786:Quality Control; D012015:Reference Standards; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D021241:Spectrometry, Mass, Electrospray Ionization / Q000379:methods; D053719:Tandem Mass Spectrometry / Q000379:methods*; D013696:Temperature; D013997:Time Factors
D004338:Drug Combinations; D004176:Dipyridamole; D011239:Prednisolone