液-质联用法测定盐酸帕罗西汀片的生物等效性

Bioequivalence studies of paroxetine hydrochloride in healthy volunteers by liquid chromatography-tandem mass spectrometry

目的:建立液-质联用(LC/MS/MS)法测定人血浆中帕罗西汀浓度,研究盐酸帕罗西汀片在健康人体的生物等效性。方法:20名男性健康志愿者单剂量、自身交叉口服盐酸帕罗西汀受试片剂和参比片剂各20mg。血浆加入内标地塞米松,经醋酸乙酯提取处理,采用LC/MS/MS法测定帕罗西汀血药浓度。用DAS药动学软件计算药动学参数及评价生物等效性。结果:帕罗西汀在0.05～50μg·L-1范围内线性关系良好。受试制剂和参比制剂的AUC0-t分别为(330.6±178.5),(331.5±158.2)μg·L-1.h;AUC0--∞分别为(342.3±192.0),(343.3±173.0)μg·L-1.h;Cmax分别为(19.5±7.7),(20.1±7.8)μg·L-1;tmax分别为(5.0±0.5),(5.4±1.0)h;t1/2分别为(12.9±3.4),(12.3±3.5)h。结论:建立的方法适用于帕罗西汀药动学研究,经方差分析及双单侧t检验结果显示,两种制剂生物等效。

ORIECTIVE To establish an HPLC/MS/MS method for measuring paroxetine in human plasma,and study the bioequivalence of paroxetine hydrochloride tablet in healthy volunteers. METHODS A single oral dose of 20 mg paroxetine test or reference tablet was given to 20 healthy volunteers in a randomized cross-over study. The plasma sample was extracted by ethyl acetate with internal standard of dexamethasone, and the concentration of paroxetine in plasma was determined by HPLC/ MS/MS. The pharmacokinetic parameters as well as the relative bioavailability were measured by DAS software. RF^ULTS The good linear range of paroxetine was 0. 05~50/~g.L i. The main pharmacokinetic parameters of test and reference paroxe- tine tablets were as follows..AUG t were （330. 6 ± 178. 5）, （331.5 ± 158. 2）μgoL-1-h; AUC0-∞ were （342. 3 ± 192. 0）, （343.3 ± 173. 0）rig.L-1 -h;C,,,~ were （19. 5 ± 7. 7）, （20. 1 ± 7. 8）μg. L 1 ;tmax were （5. 0 ± 0. 5）, （5.4 ± 1.0）h;tt/2 were （12. 9 ± 3.4）, （ 12. 3 ± 3. 5）h. CONCLUSION The method was suitable {or the pharmacokinetic study of paroxetine. The statistical analysis of the results showed that the reference and test paroxetine tablets were bioequivalent.