CAJ | 학술논문

目的：建立 LC-MS/MS 法测定大鼠血浆中莲必治注射液主要有效成分亚硫酸氢钠穿心莲内酯(ASB)浓度,研究大鼠静脉注射莲必治注射液的体内药动学。方法利用甲醇提取血浆中药物,以脱水穿心莲内酯(DAG)为内标,在 Hypersil Gold C18色谱柱(50 mm×2.1 mm,1.9μm)上以流动相甲醇-水梯度洗脱,流速0.2 mL·min-1,柱温35℃,分析时间6 min。在电喷雾离子化电离源上以选择反应监测方式进行负离子检测,用于定量分析的离子反应分别为m/z 413.2→287.2(ASB)和m/z 331.2→303.3(DAG)。大鼠静脉注射80 mg·kg-1莲必治注射液,收集不同时间点血样,测定药物浓度。结果ASB血浆标准样品的线性范围为10~1000 ng·mL-1,方法定量下限为10 ng·mL-1。方法的日内和日间精密度(RSD)在6.9%和10.8%以内,日内和日间准确度分别在96.4%~103.2%和93.7%~98.0%,提取回收率为71.2%~98.9%,基质效应为88.9%~99.9%。莲必治的末端消除半衰期t1/2λ为1.72±1.24 h,表观分布容积Vd为2.33±1.98 L·kg-1,表观清除率CL为0.87±0.39 L·h-1·kg-1。结论本方法专属性好、准确度高,灵敏度高,适用于莲必治体内药动学研究。莲必治大鼠药动学研究可为莲必治注射剂安全性再评价提供参考。
목적：건립 LC-MS/MS 법측정대서혈장중련필치주사액주요유효성분아류산경납천심련내지(ASB)농도,연구대서정맥주사련필치주사액적체내약동학。방법이용갑순제취혈장중약물,이탈수천심련내지(DAG)위내표,재 Hypersil Gold C18색보주(50 mm×2.1 mm,1.9μm)상이류동상갑순-수제도세탈,류속0.2 mL·min-1,주온35℃,분석시간6 min。재전분무리자화전리원상이선택반응감측방식진행부리자검측,용우정량분석적리자반응분별위m/z 413.2→287.2(ASB)화m/z 331.2→303.3(DAG)。대서정맥주사80 mg·kg-1련필치주사액,수집불동시간점혈양,측정약물농도。결과ASB혈장표준양품적선성범위위10~1000 ng·mL-1,방법정량하한위10 ng·mL-1。방법적일내화일간정밀도(RSD)재6.9%화10.8%이내,일내화일간준학도분별재96.4%~103.2%화93.7%~98.0%,제취회수솔위71.2%~98.9%,기질효응위88.9%~99.9%。련필치적말단소제반쇠기t1/2λ위1.72±1.24 h,표관분포용적Vd위2.33±1.98 L·kg-1,표관청제솔CL위0.87±0.39 L·h-1·kg-1。결론본방법전속성호、준학도고,령민도고,괄용우련필치체내약동학연구。련필치대서약동학연구가위련필치주사제안전성재평개제공삼고。
Objective To establish a liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for the quantification of the maj or effective component of Lianbizhi inj ection (andrographolide sodium bisulphite,ASB)in rat plasma,and to investigate pharmacokinetics of ASB in rats by following single intravenous administration. Methods ASB and an internal standard dehydroandrographolide (DAG ) were extracted from plasma by using methanol and were separated on a Hypersil Gold C18 column (50 mm×2.1 mm, 1.9μm)by using gradient mobile phase of methanol and water at a flow rate of 0.2 mL·min-1 with the temperature of 35℃.The analysis lasted for 6 min.At negative electrospray ionization mode,selected reaction monitoring of the precursor-product transitions m/z 413.2→287.2 for ASB and m/z 331.2→303.3 for DAG was used for the quantification.Plasma was collected after rats were intravenously administered with ASB at a single dose of 80 mg · kg-1 at differenttime, and the quantification of the medicine is investigated.Results The linear calibration curve was obtained in a concentration range of 10-1 000 ng· mL-1 with a lower limit of quantification of 10 ng·mL-1.Intra-and inter-day precision was less than 6.9% and 10.8% respectively.Intra-and inter-day accuracy fell in the ranges of 96.4%-103.2% and 93.7%-98.0% respectively.The recovery ranged from 71.2% to 98.9%,and the matrix effects from 88.9% to 99.9%.Pharmacokinetic parameters were obtained,t1/2λof 1.72±1.24 h,V of 2.33±1.98 L·kg-1 , CL of 0.87±0.39 L·h-1 ·kg-1 .Conclusion The study on specific,accurate,sensitive and suitable for in vivo pharmacokinetic experiment of Lianbizhi. pharmacokinetics of Lianbizhi inj ection in rats provides valuable information for safety reevaluation of Chinese medicine inj ection.