Development and optimization of a supercritical fluid chromatography tandem mass spectrometry method for the high-throughput determination of nimodipine in beagle plasma.

Abstract

A simple, sensitive, and efficient supercritical fluid chromatography with tandem mass spectrometry method was established for the determination of nimodipine in beagle plasma. One-step protein precipitation with acetone was used to extract the analytes from the plasma. Nitrendipine was used as the internal standard. The chromatographic separation was achieved on an ACQUITY UPC2 ™ BEH 2-EP column, and a gradient elution program was applied at a flow rate of 1.5mL/min. The detection was carried out on a triple quadrupole tandem mass spectrometer with an electrospray ionization source operating in positive ion mode. Quantification was performed using multiple reaction monitoring of the transitions of m/z 419.3→301.3 for nimodipine and m/z 361.4→315.2 for nitrendipine. A satisfactory linearity was obtained over the concentration range of 0.5-800ng/mL (r>0.996). The intra- and interday precision and accuracy results were <9.1% across the quality control levels. The peak concentration and area under concentration-time curve (0-720 min) values of the test and reference formulations were 279.28±211.46 and 265.13±149.26ng/mL, 25608.00±17553.65 and 28553.67±20207.92ng·min/mL, respectively. The validated method was successfully applied to reveal the pharmacokinetic profiles of nimodipine in beagle dogs after oral administration. Moreover, the analytical method could be used for further bioequivalence studies.