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虫草素及其代谢物3′-脱氧肌苷在大鼠体内的药动学OACSTPCD

Pharmacokinetics of Cordycepin and Its Metabolite 3′-Deoxyinosine in Rats

中文摘要英文摘要

目的 建立血浆虫草素及代谢物 3'-脱氧肌苷(3′-Deo)的液相色谱-串联质谱(LC-MS/MS)测定方法,研究其在大鼠体内的药动学.方法 以 2-氯腺苷(2-Chl)为内标,甲醇沉淀蛋白,色谱柱为 Kinetex C18(3 mm×100 mm,2.6 μm),流动相为水(5 mmol·L-1乙酸铵)-甲醇溶液,梯度洗脱.电喷雾离子源,正离子多反应监测.研究大鼠灌胃虫草素(10 mg·kg-1)后血浆虫草素及 3′-Deo药动学.结果 虫草素和 3′-Deo分别在 0.5~100 和 1~200 ng·mL-1范围内线性关系良好,定量下限分别为0.5 和1 ng·mL-1.大鼠灌胃虫草素后,血浆虫草素浓度较低,主要转化为3′-Deo.虫草素和 3′-Deo的峰浓度(Cmax)分别为(5.4±3.4)和(142.0±50.0)ng·mL-1,血药浓度-时间曲线下面积(AUC0-360 min)分别为(658.4±459.3)和(18 034.9±4 981.1)ng·min·mL-1.结论 该方法简单、灵敏、准确,适用于虫草素与 3′-Deo血药浓度测定及药动学研究.

Objective To establish a method of LC-MS/MS for determining cordycepin(Cor)and 3′-deoxyinosine(3′-Deo)concentration in rat plasma,and to study their pharmacokinetics in rats.Methods Protein was precipitated with methanol using 2-chloadenosine(2-Chl)as an internal standard.The chromatography was performed on Kinetex C18(3 mm×100 mm,2.6 μm,Phenomenex,USA)with gradient elution in aqueous(5 mmol·L-1 ammonium acetate)-methanol solution as mobile phase.ESI ion source was used for mass spectrometry,and positive ion multiple reaction monitoring(MRM)was used for scanning detection.The pharmacokinetics of Cor and 3′-Deo after oral administration of Cor(10 mg·kg-1)were studied in rats.Results Cor at 0.5-100 ng·mL-1 and 3′-Deo at 1-200 ng·mL-1 had good linearity,and the lower limits of quantification were 0.5 and 1 ng·mL-1,respectively.After oral administration of Cor in rats,the plasma concentration of Cor was low,which was mainly converted into the metabolite 3′-Deo.The Cmax of Cor and 3′-Deo were(5.4±3.4)and(142.0±50.0)ng·mL-1,and AUC0-360min min were(658.4±459.3)and(18 034.9±4 981.1)ng·min·mL-1,respectively.Conclusion The method is simple,sensi-tive,and accurate,which is suitable for determining Cor and 3′-Deo concentration in plasma and the pharmacokinetic study.

胡楠;蒋振伟;钱敏燕;张雯婷;陈陆俊;郑晓;应汉杰;蒋敬庭

苏州大学附属第三医院药学部,常州 213000||苏州大学附属第三医院肿瘤生物诊疗中心,常州 213000苏州大学附属第三医院药学部,常州 213000苏州大学附属第三医院肿瘤生物诊疗中心,常州 213000南京工业大学生物与制药工程学院,南京 211816

中医学

虫草素3′-脱氧肌苷药动学液相色谱-串联质谱法

Cordycepin3′-deoxyinosinePharmacokineticsLiquid chromatography tandem mass spectrometry

《医药导报》 2024 (003)

345-351 / 7

国家自然科学基金资助项目(32270955,81972869);江苏省中医药科技发展计划(ZT202115);江苏省科技计划专项资金(重点研发计划社会发展)项目(BE2022719);常州市社会发展科技支撑资金项目(CE20215030);常州市科技基础设施建设计划-常州市临床药学重点实验室(CM20223005).

10.3870/j.issn.1004-0781.2024.03.003

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