摘要
目的 :进行高效液相色谱 质谱联用测定人血浆中尼索地平浓度的方法学及其不同制剂的药代动力学研究。方法 :采用高效液相分离系统 ,流动相为甲醇 水 醋酸 ,流速为 1ml·min-1,分流比 2 :1,固定相为HypersilC18柱。采用质谱检测系统 ,AP ESI正离子模式 ,雾化压力 0 .0 5 4Pa(40 0psi) ,保护气N210L·min-1,毛细管电压 4 0 0 0V ,离子源温度10 0℃ ,碎片电压为 2 2 0V ,离子采集方式为选择性离子检测 ,尼索地平采集质荷比为 4 11(M +Na) ,尼莫地平为 4 41(M +Na)。以尼莫地平为内标 ,测定尼索地平血浆浓度 ,计算其药动学参数。结果 :在 0 .2～ 5 0 μg·L-1范围内 ,尼索地平血浓度呈线性关系 ,最低检测浓度为 0 .15 μg·L-1,回收率在 72 .6 %以上 ,日内、日间的RSD均小于 9.8%。单剂量给药 ,尼索地平缓释片、缓释胶囊和普通片半衰期 (t1 2 ,h)分别为 6 .0 8± 1.4 8、7.0 6± 1.80、3.70± 0 .2 5 ;血浓度峰值 (Cmax,μg·L-1)分别为 3.4 3± 0 .5 5、3.71±0 .2 4、9.18± 3.78;达峰时间 (Tmax,h)分别为 5 .4 1±0 .72、5 .83± 0 .4 4、2 .0 2± 0 .2 3;时间曲线下面积(AUC0 -t,μg·h-1·L-1)分别为 31.11± 5 .0 0、33.6 3±7.16、32 .72± 5 .0 9;缓释片与缓释胶囊的相对生物利用度 (F)分别为
AIM: To determine the concentration of nisoldipine in human plasma by HPLC-MS method and investigate the pharmacokinetics of sustained and immediate-release preparations. METHODS: A C 18 column was used to separate nisoldipine from plasma with the mobile phase of a mixture of methanol-water-acetic acid (7525 0.1) at a flow rate of 1.0 ml·min -1. MS: atmospheric pressure electronic spray ionization (AP-ESI) and ion mass spectral (m/z) of 411 were selected to quantify nisoldipine. Internal standard (IS): atmospheric pressure electronic spray ionization and m/z of 441 for nimodipine. RESULTS: The linear range of the standard curve of nisoldipine was 0.2- 50 μg·L -1 and the determination limit was 0.15 μg·L -1. The recovery rate was more than 70%, and intra-day relative standard deviation (RSD) and inter-day RSD were less than 10%. After being given a single dose of 10 mg nisoldipine sustained release tablet, sustained release capsule and normal tablet, the half life(t 1/2 /h) were 6.08± 1.48, 7.06± 1.80 and 3.70± 0.25, the time to peak concentration (T peak /h) were 5.4± 0.7, 5.8± 0.4 and 2.0± 0.2, the peak concentration (C max / μg·L -1) were 3.43± 0.55, 3.71± 0.24 and 9.18± 3.78, the area under time- concentration curve (AUC 0-t / μg·h -1·L -1) were 31.10± 5.00, 33.63± 7.16 and 32.72± 5.09. But after being given multiple doses of nisoldipine, C max/ μg·L -1 were 5.20± 0.27, 3.91± 0.22 and 5.30± 1.04, C min / μg·L -1 were 0.72± 0.10, 0.77± 0.07 and 0.53± 0.07, DF were 175.00%± 16.34%, 177.10%± 18.43% and 247.92%± 57.71% respectively. The bioavailability of sustained- release tablet and capsule were 96%±12% and 102%±9% respectively. CONCLUSION: The determination of concentration of nisoldipine in human plasma by HPLC-MS method is sensitive and accurate. It can be used for the investigation of the bioavailability and pharmacokinetic of nisoldipine.
出处
《中国临床药理学与治疗学》
CAS
CSCD
2004年第9期1002-1006,共5页
Chinese Journal of Clinical Pharmacology and Therapeutics
