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目的:建立人血浆中利巴韦林的HPLC-MS分析方法,用以测定18名健康男性受试者舌下含服不同厂家的利巴韦林含片后的血药浓度,估算受试制剂和参比制剂的药动学参数,评价两种制剂是否生物等效。方法:采用双周期随机交叉试验设计。分别给予18名男性健康受试者试验制剂或参比制剂80mg,采集静脉血样,血浆样品去蛋白后用HPLC/MS/MS法检测药物浓度。计算药动学参数,判定两制剂是否生物等效。结果:测定利巴韦林的线性范围为2～500ng/mL(r2为0.9944),平均回收率>90%,日内RSD和日间RSD均<10%。测得血浆中两种制剂的利巴韦林的主要药代动力学参数tmax、Cmax、t1/2、AUC0-72和AUC0→∞分别为:(1.1±0.5)、(1.1±0.4)h,(249±89)、(232±65)ng/mL,(34±11)、(34±11)h,(2828±1215)、(2685±1096)ng.h.mL-1,(3600±1568)、(3416±1379)ng.h.mL-1。以AUC0-72计算,利巴韦林含片的相对生物利用度平均为(106±16)%。结论:本方法更简便、准确,灵敏度得到很大提高。两种制剂的利巴韦林药代动力学参数无统计学差异,具有生物等效性。
OBJECTIVE: To establish an HPLC-MS method for the analysis of ribavirin in human plasma. The method was used to determine the plasma concentrations of ribavirin buccal tablets from different manufacturers after sublingual administration in 18 healthy male subjects. And the pharmacokinetic parameters of the reference formulation to assess whether the two formulations are bioequivalent. Methods: Double-cycle randomized crossover design. Eighteen male healthy subjects were given 80 mg of test or reference preparations respectively, and venous blood samples were collected. After the plasma samples were deproteinized, the drug concentrations were determined by HPLC / MS / MS. Pharmacokinetic parameters were calculated to determine whether the two formulations were bioequivalent. Results: The linear range of ribavirin was 2 ~ 500 ng / mL (r2 = 0.9944). The average recovery was> 90%. The intraday RSD and daytime RSD were all less than 10%. The main pharmacokinetic parameters tmax, Cmax, t1 / 2, AUC0-72 and AUC0 → ∞ of ribavirin measured in plasma were (1.1 ± 0.5), (1.1 ± 0.4) h, (249 ± 89), (232 ± 65) ng / mL, (34 ± 11), (34 ± 11) h, (2828 ± 1215), (2685 ± 1096) ng.h.mL- 1568), (3416 ± 1379) ng.h.mL-1. In terms of AUC0-72, the relative bioavailability of ribavirin buccal tablets was (106 ± 16)% on average. Conclusion: The method is more simple, accurate and the sensitivity is greatly improved. The ribavirin pharmacokinetic parameters of the two formulations showed no statistical difference and were bioequivalent.