摘要
目的:建立液相色谱-质谱(HPLC-MS)法测定人血浆中赖诺普利的浓度,并用于其生物等效性研究。方法:以依那普利拉为内标,采用Thermo Hypersil-HyPURITY C_(18)色谱柱,流动相为0.1%甲酸-甲醇-乙腈(58:25:17),HPLC-MS采用电喷雾离子化(ESI),选择正离子检测模式。结果:赖诺普利在2.5~320μg·L^(-1)浓度范围内线性关系良好。18名受试者单次服用20mg赖诺普利受试制剂或参比制剂后的主要药动学参数AUC_(0~48),AUC_(0~∞),t_(max),c_(max)分别为(1062±s 212)和(1055±214)μg·h·L^(-1),(1115±221)和(1136±224)μg·h·L^(-1),(6.1±0.6)和(6.1±0.5)h,(109±25)和(115±27)μg·L^(-1)。受试制剂对参比制剂的相对生物利用度为(101±13)%。结论:该方法灵敏度高,无杂质干扰,结果准确。测得受试制剂与参比制剂的主要药动学参数之间无显著差异,2种制剂生物等效。
AIM: To determine the concentration of lisinopril in human plasma with HPLC-MS method for pharmacokinetics study and bioequivalence evaluation. METHODS: A Thermo Hypersil-HyPURITY Cls column was used with enalaprilat as internal standard and 0.1% formic acid-methanol-acetonitrile (58 : 25 : 17) as the mobile phase. The analytes were ionized in the electro spray ionization (ESI) ion source of the mass spectrometer and detected in the selected ion monitoring (SIM) mode. RESULTS: The calibration curve of lisinopril was linear over the range of 2.5~320μg·L^-1. The pharmacokinetic parameters, AUCo-48, AUCo-∞, Tmax and Cmax of 18 subjects after taking a single dose of the trial preparation (20 mg) or the reference preparation (20mg) were (1062±s212) and (1 055±214)μg·L^-1, (1115±221) and (1 136±224)μg·h·L^-1, (6.1 ± 0.6) and (6.1 ± 0.5) h, (109 ± 25) and (115 ± 27)μg·L^-1, respectively. The relative bioavailability was (101 ± 13) %. There were no significant difference of main pharmaeokinetie parameters between the trial preparation and the reference preparation. CONCLUSION: The method is accurate and sensitive with no endogenous interference. The two formulations are bioequivalent.
出处
《中国新药与临床杂志》
CAS
CSCD
北大核心
2007年第6期436-439,共4页
Chinese Journal of New Drugs and Clinical Remedies
关键词
赖诺普利
依那普利拉
色谱法
高压液相
光谱法
质谱
电喷雾电离
药动学
生物等效性
lisinopril
enalaprilat
chromatography, high pressure liquid
spectrometry, mass,electrospray ionization
pharmacokinetics
bioequivalence