Simultaneous Determination of Felodipine and Metoprolol in Beagle Dog Plasma by Online SPE-LC-MS/MS and Its Application in a Pharmacokinetic Study

In order to overcome deficiencies for simultaneously determining felodipine (FDP) and metoprolol (MPL) with low recovery and low sensitivity, a new online SPE coupled with the liquid chromatography–tandem mass spectrometry (SPELC-MS/MS) method for the simultaneous quantitative determination of FDP and MPL in beagle dog plasma was established. The SPE extraction of FDP and MPL was performed on a Retain PEP Javelin column (10 × 2.1 mm, 5 μm), while the chromatographic separation was achieved on a ZORBAX SB-C18 (50 × 2.1 mm, 3.5 μm) analytical column. Multiple reaction monitoring operated in the positive ion mode was adopted in MS detection, and the precursors to the product ion transition values of m/z 384/338.1, 268/74.2 and 436.2/207.1 were used to measure FDP, MPL and the internal standard (valsartan). The high throughput, accurate and sensitive method for FDP and MPL was validated and applied to the bioavailability research of FDP and MPL in beagle dogs.