摘要
目的:建立一种快捷、灵敏的高效液相色谱法测定大鼠血浆中的厄他培南,并考察其在大鼠体内的药动学。方法:以甲硝唑为内标,血浆样品经过甲醇沉淀蛋白,离心,取上清液进行HPLC分析。使用Diamonsil C_(18)(4.6 mm×150 mm,5.0μm)色谱柱,流动相为乙腈-10 mmol·L^(-1)醋酸钠溶液(11.4:88.6),流速1.0 m L·min^(-1),检测波长295 nm,柱温35℃,进样量10μL。结果:血浆中厄他培南浓度在2~200μg·m L^(-1)范围内线性关系良好(r=0.999 8);厄他培南的绝对回收率为(96.4±1.7)%^(99.3±1.2)%,方法回收率为(87.6±3.1)%^(107.9±2.5)%;内标甲硝唑的绝对回收率为(98.1±1.9)%;日内、日间精密度均小于5%;中浓度的血浆样品在常温放置3 h、-40℃保存7 d及反复冻融3次,均能保持稳定;稀释效应精密度为0.4%。大鼠静脉注射厄他培南100 mg·kg^(-1)后的主要药动学参数分别为AUC_(0→t)(207.9±19.7)μg·h·mL^(-1),AUC_(0→∞)(209.1±20.4)μg·h·mL^(-1),t_(1/2)(0.4±0.05)h,CL(0.48±0.05)L·(h·kg)^(-1),V(0.29±0.02)L·kg^(-1)。结论:此HPLC法测定大鼠体内厄他培南浓度,方法准确快捷,灵敏度高,重复性好,适合该药的药动学研究。
Objective： To establish a rapid, sensitive method for the determination of ertapenem in rat plasma, and its preliminary pharmacokinetics in rats was also investigated. Methods： Taking metronidazole as an internal standard, the plasma samples were extracted by methanol to precipitate protein. After centrifugation, the supernatant was analyzed by HPLC. A Diamonsil C18 （ 4.6 mm × 150 mm, 5.0μ m ） column was used, with the mobile phase of acetonitrile-10 mmol· L-1 sodium acetate solution（ 11.4：88.6 ）, flow rate of 1 mL·min-1, detection wavelength of 295 nm, column temperature of 35 ℃, sample volume of 10μL. Results： The method was validated over the concentration range of 2-200 μg· mL-1 for ertapenem in rat plasma, and there was excellent linearity （ r=0.999 8 ）. The extraction recoveries for ertapenem were （ 96.4 ± 1.7 ） %- （ 99.3 ± 1.2 ） %, while its method recoveries were （ 87.6± 3.1 ） %- （ 107.9± 2.5 ） %. The extraction recovery for the internal standard metronidazole was （ 98.1 ±1.9 ） %;the intra-day and inter-day RSDs were both below 5% ; All the analytes of medium concentrations in serum were stable at room temperature for 3 h at-40 ℃ for 7 days and after three-cycle freeze-thaw; Effect of dilution RSD was 0.4%. The major pharmacokinetic parameters after iv administration of ertapenem 100 mg·kg-1 to rats were as follows： AUC0→t（ 207.9 ＋ 19.7 ） μg· h· mL-1, AUC0→∞ （ 209.1 ± 20.4 ） μg· h· mL-1, t/n（ 0.4 ± 0.05 ）h, CL （ 0.48± 0.05 ） L· （ h·kg ）-1, V（ 0.29 ±0.02 ） L· kg-1. Conclusion： HPLC method for the determination of ertapenem concentration in plasma is rapid, simple, accurate and sensitive, which is also suitable for pharmacokinetic study.
出处
《药物分析杂志》
CAS
CSCD
北大核心
2017年第11期2082-2086,共5页
Chinese Journal of Pharmaceutical Analysis
