Résumé
OBJECTIVE: To establish a method for determining nine residual solvents in cefotetan disodium by headspace gas chromatography. METHODS: The residual solvents including methanol, acetone, acetonitrile, dichloromethane, butanone, ethyl ace-late, tetrahydrofuran in cefotetan disodium were quantitatively determined on a DB-624 column (30 m×0.32 mm, 1.8 μm). Water was solvent media. The residual solvents of anisole and isocaprylic acid in cefotetan disodium were quantitatively determined on a HP-FFAP column (25 m×0.32 mm, 0.5 μm). The 20% dimethylsulfoxide (DMSO) was used as the solvent. RESULTS: Nine residual solvents were completely separated. Good linearity of the solvents were obtained within the determination ranges. There between 0.9988 and 0.9997. The average recoveries of three levels were in the range of 95.71%-103.55%. The RSDs were 0.39%-2.28%. CONCLUSION: The established two methods are accurate and sensitive, and can be used for the determination of residual solvents in cefotetan disodium.
Résumé
OBJECTIVE: To study the pharmacokinetics of cefotetan disodium for injection in Chinese healthy volunteers. METHODS: Thirty healthy volunteers were randomly divided into 3 groups with 5 males and 5 females in each group. The volunteers in each group were administered a single dose of cefotetan disodium of 0.5, 1.0, or 2.0 g, respectively. Those who got dose of 1.0 g were administered twice daily for 7 d. The concentrations of cefotetan disodium in plasma were determined by HPLC while the pharmacokinetic parameters were calculated by DAS software. RESULTS: The main pharmacokinetic parameters of cefotetan disodium after single-dose intravenous administration were as follows: ρmax(68.03 ± 15.95), (110.77 ± 17.67), (225.34 ± 19.63) mg · L-1; AUC0-15(242.88 ± 56.60), (415.22 ± 54.24), (856.18 ± 82.72) mg · h · L-1; t1/2(3.67 ± 0.48), (3.69 ± 0.40), (3.53 ± 0.26) h, respectively. The main pharmacokinetic parameters of cefotetan disodium after multiple-dose administration were as follows: ρmax(123.60 ± 15.74) mg · L-1; AUC0-15 (444.38 ± 62.78) mg · h · L-1; AUCSS(426.87 ± 59.36) mg · h · L-1; t1/2(3.29 ± 0.36) h; ρav(35.57 ± 4.95) mg · L-1, respectively. CONCLUSION: Cefotetan disodium for injection displays linear pharmacokinetics in the dose range of 0.5 to 2.0 g after single intravenous dosing. There is no significant accumulation after repeated dosing. There is no significant difference in the pharmacokinetic parameters between female and male subjects. Copyright 2012 by the Chinese Pharmaceutical Association.