Determination of (S)-Pantoprazole Sodium in Dog Plasma by LC-MS/MS and Its Toxicokinetic Study / 中国药学杂志

ABSTRACT

OBJECTIVE: To establish an LC-MS/MS method to determine (S)-pantoprazole sodium in dog plasma and investigate its toxicokinetics. METHODS: After protein precipitation with acetonitrile, the analyte and internal standard were separated on CHIRALCEL OJ-RH column (4.6 mm ×150 mm, 5 μm) with acetonitrile-water (28∶72) as mobile phase eluted at a flow rate of 0.6 mL·min-1. Detection was carried out by electrospray positive ionization mass spectrometry in the multiple reaction monitoring (MRM) mode. The MRM transitions of m/z 384.0/199.8 and m/z 180.0/110.0 were used to quantify (S)-pantoprazole sodium and phenacetin, respectively. Beagle dogs were intravenously given (S)-pantoprazole sodium for 4 weeks at low, medium, and high dosages (10, 20, 40 mg·kg-1·d-1). RESULTS: The calibration curve was linear over the concentration range of 50-30 000 ng·mL-1. The RSDs were less than 15%, and the accuracy was in the range of 85%-115%. The AUC0-4 h and ρmax of (S)-pantoprazole sodium were proportional to the dosages. CONCLUSION: The established method can be applied to the determination of (S)-pantoprazole sodium in plasma of dogs and is suitable for the toxicokinetic study.