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目的:建立UHPLC-MS/MS法测定硝苯地平缓释片在比格犬血浆中的药物浓度。方法:血浆经乙醚-正己烷(2∶1)提取,以地西泮为内标,采用UHPLC-MS/MS方法测定6只比格犬口服硝苯地平缓释片20 mg后血浆中的药物浓度。UHPLC条件:采用Shim-pack XR-ODS色谱柱(75 mm×3.0 mm,2.2μm),以甲醇(B)-0.05%甲酸水(A)为流动相,洗脱梯度(0~2.00 min,80%B→95%B;2.01~2.20 min,95%B;2.21~3.50 min,80%B),流速0.4 mL·min-1,柱温40℃,分析时间总计3.50 min,进样量5#L;MS条件:硝苯地平:m/z 347.0→m/z 315.0,DP为58 V,CE为10 V,CXP为21 V;地西泮(内标):m/z285.0→m/z 193.1,DP为80 V,CE为43 V,CXP为20 V。结果:硝苯地平在浓度为0.15~50.00 ng·mL-1范围内线性关系良好(r=0.9983),日内精密度RSD(n=6)≤6.6%,日间精密度RSD(n=6)≤13.8%,绝对回收率(n=6)为63.1%~68.3%,基质效应(n=6)RSD≤7.5%。6只比格犬口服硝苯地平缓释片20 mg后的主要药动学参数T max为(4.58±1.39)h,C max为(30.53±7.38)ng·mL-1,t1/2为(8.69±3.42)h,AUC0-t为(185.9±113.3)ng·h·mL-1,AUC0-∞为(188.8±113.6)ng·h·mL-1。结论:本方法简单、快速、灵敏,重现性好,可用于测定硝苯地平缓释片的血药浓度并进行药动学评价。
OBJECTIVE: To establish a method for the determination of the drug concentration of nifedipine sustained-release tablets in Beagle dog plasma by UHPLC-MS / MS. Methods: The plasma was extracted with diethyl ether-n-hexane (2: 1), and the internal standard of diazepam was determined by UHPLC-MS / MS. concentration. UHPLC conditions: The mobile phase was eluted with a Shim-pack XR-ODS column (75 mm × 3.0 mm, 2.2 μm) using methanol (B) % B → 95% B; 2.01-2.20 min, 95% B; 2.21-3.50 min, 80% B) at a flow rate of 0.4 mL · min-1 at a column temperature of 40 ° C for a total analysis time of 3.50 min. L; MS conditions: nifedipine: m / z 347.0 → m / z 315.0, DP 58 V, CE 10 V, CXP 21 V; diazepam (internal standard) z 193.1, DP 80 V, CE 43 V, CXP 20 V. Results: The average nifedipine showed a good linear relationship (r = 0.9983) at a concentration range of 0.15-50.00 ng · mL-1, intraday RSD (n = 6) ≤6.6%, intraday precision RSD ≤13.8%, absolute recovery (n = 6) was 63.1% ~ 68.3%, matrix effect (n = 6) RSD≤7.5%. The main pharmacokinetic parameters of 6 beagle dogs after oral administration of 20 mg nifedipine sustained-release tablets were (4.58 ± 1.39) h, Cmax (30.53 ± 7.38) ng · mL-1 and t1 / 2 8.69 ± 3.42) h, AUC0-t was (185.9 ± 113.3) ng · h · mL-1, and AUC0-∞ was (188.8 ± 113.6) ng · h · mL-1. Conclusion: The method is simple, rapid, sensitive and reproducible. It can be used to determine the plasma concentration of nifedipine sustained-release tablets and evaluate its pharmacokinetics.