摘要
目的:建立人血浆中福辛普利及其代谢物福辛普利拉的LC-MS/MS测定方法,研究健康志愿者口服福辛普利片后的药代动力学。方法:血浆样品加入内标扎来普隆,血浆样品酸化后用乙醚-二氯甲烷(3∶1)混合溶剂提取处理,LC-MS/MS分析。流动相为甲醇-10mmol/L醋酸胺水溶液,色谱柱为LichrospherC8,梯度洗脱,流速1.0mL/min,柱温25℃。质谱检测方式:选择性反应检测(SRM),20名健康受试者口服20mg福辛普利钠片,计算主要药代动力学参数。结果:福辛普利在0.1～15.0ng/mL,福辛普利拉1.0～700ng/mL范围内线性关系良好。福辛普利的日内RSD小于3.7%,日间RSD小于6.9%;福辛普利拉的日内RSD小于2.4%,日间RSD小于5.2%。福辛普利与福辛普利拉的t1/2分别为(2.72±1.75)h和(7.25±0.81)h,cmax分别为(4.61±2.34)ng/mL和(409.43±136.28)ng/mL,tmax分别为(1.21±0.42)h和(3.74±0.87)h。结论:本方法灵敏度高,测定结果准确,可用于人体药代动力学及相对生物利用度研究。
Aim： To establish a LC-MS/MS method for the simultaneous determination of plasma fosinopril and its major active metabolite fosinoprilat concentrations in human pharmacokinetic studies. Methods：After adding zaleplon （internal standard）, plasma samples were extracted by ether-dichloromethane （3：1） and then determined by LC-MS/MS. The separation was carried out on a Lichrospher C8 （4.6 mm×250 mm,5 μm） at 25 ℃ ,with gradient elution at a flow rate of 1.0 mL/min. Methanol was used as eluent A and 10 mmol/L ammonium acetate aqueous was used as eluent B. The gradient procedure was as follows： from 0 min to 2.0 min, 40% B;from 2.01 min to 10.0 min, 40% B. HPLCMS/MS was monitored in the mode of selected reaction monitoring （SRM） mode. A single oral dose of 20-mg fosinopril sodium tablets was administered to 20 healthy subjects. Results： Linearity between the observed response and the con- centration was found with fosinopril and fosinoprilat over the concentration range of 0.1 - 15 ng/mL and 1.0 - 700 ng/ mL for fosinopril and fosinoprilat, respectively. Intra-day and inter-day precisions （expressed as RSD） in the method were less than 3.7% and 6.9% for fosinopril and less than 2.4% and 5.2% for fosinoprilat, respectively. For fosino- pril, the main pharmacokinetic parameters t1/2, tmax and cmax were found to be （2.72 ± 1.75） h, （1.21 ± 0.42） h and （4.61 ± 2.34） ng/mL, respectively. For fosinoprilat, the main pharmacokinetic parameters t1/2, tmax and cmax were （7.25 ± 0.81 ） h, （ 3.74 ± 0.87） h and （409.43 ± 136.28） ng/mL, respectively. Conclusion： The assay was proved to be sensitive, accurate and convenient. It can be applied to study the phannacokinetics and bioavailability of fosinopill and fosinoprilat formulations in humans.
出处
《中国药科大学学报》
CAS
CSCD
北大核心
2007年第4期347-351,共5页
Journal of China Pharmaceutical University
