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.
ABSTRACT
OBJECTIVE: The systemic toxicities of S-(-)-pantoprazole sodium in rats following intravenous injuction for 30 d were studied. METHODS: One hundred rats were divided randomly into 5 groups: vehicle control group, pantoprazole sodium control group and three S-(-)-pantoprazole sodium groups with different dosages, and received vehicle, pantoprazole sodium(80 mg·kg-1·d-1), S-(-)-pantoprazole sodium(80, 40 and 20 mg·kg-1·d-1) by i.v.via tail vein. Administrations were performed each day for consecutive 30 d. Haematological parameters, biochemical parameters, and histopathology analysis were determined at 30 d of treatments and 14 d after the withdrawal, respectively. RESULTS: The rats in the S-(-)-pantoprazole sodium group at 80 mg·kg-1·d-1 apperanced shortness of breath, unsteady gait, lying motionless and other symptoms. The levels of TC, Na+, Cl- in this group were significantly higher or lower than those in vehicle control group at 30 d(P<0.05), The change of these parameters regained to normal at 14 d after withdrawal. CONCLUSION: Intravenous administration of the S-(-)-pantoprazole sodium for 30 d at high dose could induce reversible damage to liver and electrolyte. The toxicity of S-(-)-pantoprazole sodium is similar with pantoprazole sodium at the same dosage.