摘要
建立了高效液相色谱法(HPLC)测定血浆中氯解磷定(PAM)的含量,研究了不同给药方式对大鼠体内药代动力学行为的影响。优化条件为:色谱柱CAPCELL PAK C18 MGⅢ(250 mm×4.6 mm,5μm),以5 mmol/L正庚烷磺酸钠溶液(含体积比0.12%三氟乙酸)-乙腈为流动相进行梯度洗脱,流速1 mL/min,检测波长294 nm,内标双复磷。血浆中PAM浓度在0.5~100 mg/L范围内与PAM和内标峰面积之比具有良好的线性关系,相关系数为0.9996。方法日内精密度分别为7.1%,3.3%,3.6%,日间精密度分别为9.1%,9.7%,7.1%,重复性相对标准偏差(RSD)为0.76%,可用于血浆中PAM的含量测定。药代动力学结果表明,相比静脉注射组,肌内注射组药物半衰期和平均滞留时间延长。肌内注射PAM更适用于急性中、重度有机磷中毒的临床治疗。
A high-performance liquid chromatography(HPLC)method was established for the determination of pralidoxime chloride(PAM)in rat plasma,and the effects of different administration methods on the pharmacokinetic profiles of rats were investigated.The optimized conditions were as follows:CAPCELL PAK C18 MGⅢ(250 mm×4.6 mm,5μm)as the chromatographic column,gradient elution with 5 mmol/L sodium nheptane sulfonate solution(containing the volume ratio of 0.12%trifluoroacetic acid)-acetonitrile as mobile phase,the flow rate of 1 mL/min,294 nm as detection wavelength,and obidoxime for internal standard.The PAM concentration and the ratio of the peak area of the PAM to the obidoxime showed a good linear relationship with a correlation coefficient of 0.9996 in the ranges of 0.5-100 mg/L in plasma.The intra-day precisions were 7.1%,3.3%and 3.6%,and the inter-day precisions were 9.1%,9.7%and 7.1%,respectively.The relative standard deviation(RSD)of repeatability was 0.76%.The HPLC method can be used for the determination of PAM in rat plasma.Pharmacokinetic studies showed that the half-life and the mean residence time prolonged in intramuscular injection group compared to intravenous injection.Intramuscular injection of PAM was more suitable for moderate or severe organophosphorus poisoning in clinical practice.
作者
蔡啟梅
冯数橙
王涛
全东琴
王永安
申辽
马兵
CAI Qimei;FENG Shucheng;WANG Tao;QUAN Dongqin;WANG Yongan;SHEN Liao;MA Bing(School of Chemistry and Chemical Engineering,Key Laboratory of Medical Molecule Science and Pharmaceutics Engineering,Ministry of Industry and Information Technology,Beijing Institute of Technology,Beijing 100081,China;State Key Laboratory of Highly Toxic Substances for Anti-Drug Research,Institute of Pharmacology and Toxicology,Academy of Military Medical Sciences,Beijing 100850,China)
出处
《分析试验室》
EI
CAS
CSCD
北大核心
2023年第2期167-171,共5页
Chinese Journal of Analysis Laboratory
基金
国家自然科学基金项目(82001936)资助。
关键词
高效液相色谱
氯解磷定
含量测定
药代动力学
high performance liquid chromatography
pralidoxime chloride
content determination
pharmacokinetics