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建立人血浆中依那普利的高效液相色谱-质谱测定方法,用于研究依那普利片的人体相对生物利用度。方法:血浆样品中加入内标阿普唑仑后,离心取上清液上固相革取小柱,以甲醇洗脱,采用高效液相色谱-质谱法,电喷雾电离源正源选择离子峰检测。色谱柱为ODS c_(18),流动相为甲醇-0.1％甲酸(45∶55),流速为0.8mL·min~(-1),毛细管电喷雾电压:3.81KV,取样锥孔电压:39.00V。用建立的方法测定16名健康男性志愿者单剂量口服依那普利片实验制剂或参比制剂的体内经时过程,由血药浓度数据获得各自的主要药动学参数,以双单侧t检验进行生物等效性半定。结果:依那普利在2.5～400ng·mL~(-1)范围内呈良好的线性关系,r=0.9996,平均回收率为102.2％,日内RSD≤4.6％,日间RSD≤8.2％。16名健康男性志愿者单次服用20mg依那普利片实验制剂或通用比制剂后的药动学参数AUC_(0-6)、C_(max)、T_(1/2)分别为(322.6±79.1)和(325.1±70.5)ng·h·mL~(-1)、(229.8±54.4)和(237.3±48.1)ng·mL~(-1)、(1.80±0.60)和(1.50±0.30)h。相对生物利用度为(99.7±8.2)％。结论:该方法灵敏度高,无杂质干扰,结果准确。测得的实验制剂与参比制剂的主要药动学参数之间无明显差异,2种片剂为生物等效制剂。
A HPLC method for the determination of enalapril in human plasma was developed to study the relative bioavailability of enalapril in humans. Methods: Plasma samples were treated with alprazolam internal standard and centrifuged to collect the solid phase on the supernatant column. The column was eluted with methanol. High performance liquid chromatography-mass spectrometry (ESI-MS / MS) Detection. The mobile phase consisted of methanol-0.1% formic acid (45:55), the flow rate was 0.8mL · min -1, the capillary electrospray voltage was 3.81KV, the sampling cone pressure was 39.00V . The established method was used to determine the in vivo time course of single-dose oral enalapril tablets or reference preparations in 16 healthy male volunteers. The main pharmacokinetic parameters were obtained from plasma concentration data, Test for bioequivalence semi-definite. Results: Enalapril had a good linear relationship in the range of 2.5-400 ng · mL -1, r = 0.9996. The average recovery was 102.2%. The intraday RSD was lower than 4.6% and the intraday RSD was less than or equal to 8.2%. The pharmacokinetic parameters AUC_ (0-6), C_ (max), and T_ (1/2) of 16 healthy male volunteers after single administration of enalapril tablet or general-purpose preparation were (322.6 ± 79.1) and (325.1 ± 70.5) ng · h · mL -1, (229.8 ± 54.4) and (237.3 ± 48.1) ng · mL -1, 1.80 ± 0.60 and 1.50 ± 0.30, h The relative bioavailability was (99.7 ± 8.2)%. Conclusion: The method has high sensitivity, no impurity interference and accurate results. There was no significant difference in the main pharmacokinetic parameters between the experimental and reference preparations measured, and the two tablets were bioequivalent.