LC-MS determination of sulbactam in Beagle dog plasma and study on its pharmacokinetics when co-administrated with ceftazidime

Aim: To develop an LC-MS method to determine sulbactam concentration and to study pharmacokinetics of sulbactam when co-administrated with ceftazidime in Beagle dog. Method: After adding digoxin, the internal standard, the plasma samples were mixed 10 min with 1ml acetonitrile. After centrifuging, 5 μl supernatant was injected into a C₁₈ Shim-pack 250 mm × 2.0 mm I.D. column. Analysis was conducted at a flow rate of 0.2 ml/min by gradient elution. The elute from the HPLC column was directly plumbed into ESI probe. Analysis in the mass spectrometer was operated in the selected-ion monitoring model. Sulbactam concentrations in plasma were determined and pharamcokinetic parameters were also estimated. Result: The standard curve was linear in the range of 0.31 - 80.00 μg/ml with the correlation coefficient of 0.99(P<0.01). Recoveries of sulbactam at 0.62,5.00 and 80.00 μg/ml were 95.43,92.92 and 99.81% respectively. After iv Beagle dogs 13 mg/kg sulbactam and 26 mg/kg ceftazidime, the pharmacokinetic parameters of sulbactam were: AUC₃₆₀ 3865.29 ± 1115.13 μg.min/ml, t_1/257.72 ± 6.37 min, Cl 3.50 ± 0.85 ml/min/kg, V_d 0.29 ± 0.09 l/kg. After iv 13 mg/kg sulbactam, the parameters were: AUC₃₆₀ 3669.89 ± 922.17 μg^• min/ml, t_1/2 66.98 ± 11.07 min,, Cl 3.56 ± 0.75 ml/min/kg, V_d 0.34 ± 0.08 l/kg. Pharmacokinetic parameters of single sulbactam were similar to those when co-administrated with ceftazidime. Conclusion: The bioanalytical method of LC-MS is suitable for pharmacokinetic study of sulbactam. There's no significant difference between sulbactam and sulbactam/ceftazidime for injection in pharmacokinetics of sulbactam.