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目的建立高效液相色谱-质谱联用法测定血浆中辛伐他汀浓度的方法,经方法学验证其灵敏度、专属性、线性范围、精密度、准确度、稳定性和介质效应等。方法20名男性健康受试者分两组进行单剂量二交叉试验,测定天津药业焦作有限公司研制的辛伐他汀片相对于杭州默沙东制药有限公司生产的辛伐他汀片的生物利用度。单剂量口服辛伐他汀试验片(10 mg/片,4片)及辛伐他汀参比片(20 mg/片,2片)后,测定辛伐他汀的血药浓度经时过程,并计算试验制剂和参比制剂的主要药代动力学参数。结果Cm ax分别为(6.2±2.8)ng/mL和(6.0±2.6)ng/mL,Tm ax分别为(1.8±0.6)h和(1.8±0.5)h,t1/2分别为(3.4±1.1)h和(3.2±1.1)h,MRT分别为(5.2±1.2)h和(5.3±1.3)h,AUC0-14分别为(21.6±8.8)(ng.h)/m l和(21.6±8.9)(ng.h)/m l,AUC0-14分别为(23.4±9.0)(ng.h)/m l和(23.3±8.9)(ng.h)/m l;按AUC0-14计算,试验制剂中辛伐他汀片的相对生物利用度为(100.5±10.4)%;AUC和Cm ax经对数转换后方差分析检验,Tm ax经W ilcoxon符号秩检验,表明差异均无统计学意义。结论将AUC和Cm ax对数转换后经双单侧t-检验表明,试验制剂和参比制剂生物等效。
Objective To establish a method for the determination of plasma concentration of simvastatin by high performance liquid chromatography-mass spectrometry (HPLC-MS). The sensitivity, specificity, linear range, precision, accuracy, stability and medium effect of the method were verified by the methodological method. Methods Twenty healthy male subjects were divided into two groups to test the bioavailability of simvastatin tablets developed by Tianjin Pharmaceutical Jiaozuo Co., Ltd. compared with simvastatin tablets produced by Hangzhou Merck Pharmaceutical Co., Ltd. in two groups. After a single dose of simvastatin (10 mg / tablet, 4 tablets) and simvastatin reference tablets (20 mg / tablet, 2 tablets), the plasma concentration of simvastatin was measured over time, The main pharmacokinetic parameters of the formulation and the reference formulation. Results The values of Cm ax were (6.2 ± 2.8) ng / mL and (6.0 ± 2.6) ng / mL, respectively, with Tm ax of 1.8 ± 0.6 h and 1.8 ± 0.5 h, respectively, with t1 / 2 of 3.4 ± 1.1 h and 3.2 ± 1.1 h respectively. The MRT was (5.2 ± 1.2) h and (5.3 ± 1.3) h, respectively. The AUC0-14 was (21.6 ± 8.8) ng.h / ml and (21.6 ± 8.9) (ng.h) / ml and AUC0-14 (23.4 ± 9.0) (ng.h) / ml and (23.3 ± 8.9) (ng.h) / ml, respectively. According to AUC0-14, The relative bioavailability of statin tablets was (100.5 ± 10.4)%. AUC and Cm ax were logarithmically transformed and analyzed by ANOVA. Tm ax was analyzed by Wilcoxon signed-rank test, which showed no significant difference. Conclusions A logarithmic transformation of AUC and Cm ax revealed that the test formulation and the reference formulation were bioequivalent.