Development of a supercritical fluid chromatography–tandem mass spectrometry method for the determination of lacidipine in beagle dog plasma and its application to a bioavailability study

• We firstly developed a new method for the determination of lacidipine in plasma.
• Supercritical CO2 and a small amount of methanol were used for the mobile phase.
• The mobile phase was simple, low toxicity and environmental friendly.
• The method was verified and successfully applied to a pharmacokinetic study.

A simple, novel, rapid and sensitive supercritical fluid chromatography–tandem mass spectrometry (SFC-MS/MS) method was developed and validated for the determination of lacidipine in beagle dog plasma with nimodipine as internal standard. The method involved a simple liquid–liquid extraction method with tert-butyl methyl ether. The analytes were analyzed on an Acquity UPC2 with a HSS C18 SB column (3 mm × 100 mm, 1.8 μm) set at 50 °C. The mobile phase was carbon dioxide (≥99.99%) and methanol (92:8, v/v) at a flow rate of 2 ml/min, the compensation solvent was methanol with 2% formic acid at a flow rate of 0.2 ml/min and a total analysis time of 1.5 min for each sample. The multiple reaction-monitoring mode was used for quantification of ion transitions at m/z 473.32 → 354.10 and 419.00 → 343.10 for lacidipine and internal standard, respectively. The linearity range of proposed method was 0.10–100 ng/ml) (r2 ≥ 0.9990). The intra- and inter-day precision values were less than 15% and accuracy was from −0.83% to 3.27% at all quality control levels. The proposed method was successfully applied to a pharmacokinetic study of lacidipine in beagle dogs.