| objectivesA highly sensitive, specificitive, and simplely operative performance liquid chromatography-mass spectrometry method was developed and used for the determination of concentration of ribavirin in human plasma. To study pharmacokinetic characteristics of ribavirin in healthy volunteers by the main pharmacokinetic parameters to evaluate the bioequivalence and to ensure the safety and efficacy of clinical medicine.Methods18 voluneers were given a single dose and double-cross oral soft capsule of ribavirin tested and reference prepared ribavirin dose of 600mg ,and taken forearm vein blood at different time by randomized double cycle and preparations and cross-cycle test.Performance liquid chromatography-mass spectrometry method was used to determine the different moments in the ribavirin plasma concentration. Diamonsil C18 column (150×4.6 mm ID, particle size 5μm), mobile phase was methanol - water -1% formic acid (20:80:0.5, v/v), TSQ Quantum Ultra triple quadrupole tandem mass spectrometer. The Lamivudine was taken as the internal standard.To calculate the subjects and the reference preparation using major pharmacokinetic parameters, Cmax, Tmax, AUC0-t, AUC0-∞ analysis of variance and 90% confidence interval method to determine bioequivalence. ResultsThe linear range of ribavirin 10.3 - 1288ng·ml-1. The lowest limit of quantification (LLOQ) was 10.0 ng·ml-1. Recovery rate of more than 85%, days and day RSD less than 15%.Test preparation and the reference preparation pharmacokinetic parameters Tmax were 1.35±0.38 and 1.33±0.50 h; Cmax were 674.8±227.7 and 693.9±223.3 ng·ml-1, T1/2ke were 25.6±6.0 and 26.57±5.32 h; AUC0-t were 8606.2±2132.0 and8452.0±1978.8 ng·h·ml-1, AUC0-∞ were 9903.3±2494.1 and 9632.1±2404.2 ng·h·ml-1. AUC0-t in terms of soft gelatin capsules ribavirin relative bioavailability of an average of 102.2±9.5%.Evaluation of bioequivalence was made by analysis of variance and confidence interval method. The results show that the tested agents, the AUC0-t ribavirin 90% confidence interval for the reference preparation of the corresponding parameters of 97.8 - 105.9%, the AUC0-∞ ribavirin 90% confidence interval for the reference preparation of the corresponding parameters of 98.1 - 107.8%, Cmax 90% confidence interval for the reference preparation parameters corresponding to 85.8 - 109.8%.ConclusionThe method is simple, rapid and accurate.It was suitable for determination of drug concentration of ribavirin in human plasma. The bioequivalence of the two formulations may be convicted based on the above results.
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