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 1.5 mL/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 0.5–800 ng/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 ± 149.26 ng/mL, 25608.00 ± 17553.65 and 28553.67 ± 20207.92 ng·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. |