血浆苦参碱UPLC-MS/MS测定方法建立及山豆根浸膏粉经口毒代动力学研究  

Determination of matrine in rat plasma after oral administration of mountain bean root extract powder and its toxicokinetic by UPLC-MS/MS

作　　者：孙杰 刘萍 范俊沛 窦秀秀 高丹 唐黎明 SUN Jie;LIU Ping;FAN Jun-pei;DOU Xiu-xiu;GAO Dan;TANG Li-ming(Department of Pharmacology and Toxicology/Drug Safety Evaluation Center,Shanghai Institute for Food and Drug Control,Shanghai 201203,China)

机构地区：[1]上海市食品药品检验研究院药理毒理所/药物安全评价中心,上海201203

出　　处：《毒理学杂志》2024年第5期373-377,382,共6页Journal of Toxicology

摘　　要：目的 建立UPLC-MS/MS法,测定大鼠灌胃给予山豆根浸膏粉后血浆中苦参碱含量及其毒代动力学参数。方法 选取苦参碱作为毒代动力学指标物质,LC条件:采用xBridge Amide C18色谱柱(4.6 mm×100 mm,3.5μm),0.1%甲酸溶液-乙腈=60∶40 (v/v)为流动相;流速0.5 ml/min;进样体积1μl。MS条件:ESI离子源,正离子电离模式,多反应离子监测的MRM扫描方式。以1、4和12 g生药/kg剂量,1次/d,连续28 d给大鼠灌胃给予山豆根水提浸膏粉,测定大鼠体内苦参碱的浓度以及毒代动力学参数。结果 大鼠血浆中苦参碱的线性范围为10~1000 ng/ml。定量下限为10 ng/ml。批内和批间精密度良好,RSD均小于15%,准确度均在±15%以内。苦参碱在大鼠体内的Cmax、AUC随着剂量增加而增加,但不呈线性关系。苦参碱在大鼠体内存在明显雌雄差异,雌性大鼠体内苦参碱暴露量明显高于雄性大鼠。苦参碱在大鼠体内无明显蓄积,与毒性表现基本一致。结论 该法专属性强、灵敏度高、操作简便,适用于生物样本中苦参碱的测定及毒代动力学研究。Objective To establish a UPLC-MS/MS method for the quantitative determination of matrine in rat plasma and its toxicokinetic parameters after oral administration of mountain bean root extract powder.Methods Matrine was selected as the toxicity marker,LC conditions:xBridge Amide C18 column(4.6 mmx100 mm,3.5μm),0.1%formic acid solution-acetonitrile=60:40(v/v)was used as mobile phase.Flow rate:O.5 ml/min;Injection volume:lμl.MS conditions:ESI ion source,positive ion mode,MRM scan for multi-reactive ion monitoring.At the doses of 1,4 and 12 g crude drug/kg,mountain bean root extract powder was orally administered to rats once a day for 28 consecutive days,and the plasma concentration of matrine and its toxicokinetic profile were determined.Results The calibration curve for matrine had a good linearity over the range of 10~1000 ng/ml and the minimum quantitative limit was 10 ng/ml.The precisions(RSDs)of inter-and intra-batch and the accuracies(REs)were below 15%and±15%respectively.The Cmax and AUC of matrine increased with the increase of dose,but there was no linear relationship.There was a significant male-female difference in rats,with female rats having significantly higher exposure than male rats.There was no significant accumulation of matrine in rats,which was basically consistent with the toxicity.Conclusion This method is specific,sensitive,convenient and suitable for the determination of matrine in biological samples and its toxicokinetic study.

关 键 词：超高效液相色谱-串联质谱 山豆根 苦参碱 毒代动力学 

分 类 号：R99[医药卫生—毒理学] R114[医药卫生—药学]