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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 and sensitive HPLC method for the determination of ertapenem in rat plasma and investigate its pharmacokinetics in rats. Methods: Metronidazole was used as internal standard. The plasma samples were precipitated by methanol, centrifuged and the supernatant was taken for HPLC analysis. The mobile phase was acetonitrile-10 mmol·L -1 sodium acetate solution (11.4: 88.6) at a flow rate of 1.0 m L · min ~ (-1) with Diamonsil C 18 (4.6 mm × 150 mm, -1), detection wavelength 295 nm, column temperature 35 ℃, injection volume 10μL. Results: The plasma concentration of ertapenem was linear in the range of 2 ~ 200 μg · m L -1 (r = 0.999 8). The absolute recovery of ertapenem was (96.4 ± 1.7)% ~ ( 99.3 ± 1.2)%, the recovery rate was (87.6 ± 3.1)% ~ (107.9 ± 2.5)%. The absolute recovery of internal standard metronidazole was (98.1 ± 1.9)%. The intra- and inter- %. The plasma samples with medium concentration were kept at room temperature for 3 h, stored at -40 ° C for 7 days, and frozen and thawed repeatedly for 3 times, all of which remained stable. The dilution precision was 0.4%. The main pharmacokinetic parameters of rat after intravenous injection of ertapenem 100 mg · kg ~ (-1) were AUC_ (0 → t) (207.9 ± 19.7) μg · h · mL -1, AUC_ (∞ → ∞) (209.1 ± 20.4) μg · h · mL -1, t 1/2 (0.4 ± 0.05) h and CL (0.48 ± 0.05) L · (h · kg) -1 ), V (0.29 ± 0.02) L · kg -1. Conclusion: This HPLC method for the determination of rat ertapenem concentration in rats, the method is accurate and fast, high sensitivity, good repeatability, suitable for the pharmacokinetics of the drug.