液相色谱串联质谱法测定大鼠血浆中反式-橙花叔醇质量浓度  

Determination of Trans-Nerolidol in Plasma of Rats by LC-MS/MS

作　　者：佟彬良[1] 迟玉乾 颜文 赵梦然[1] 张卓[1] 周春华 TONG Binliang;CHI Yuqian;YAN Wen;ZHAO Mengran;ZHANG Zhuo;ZHOU Chunhua(Department of Pharmacy,The First Hospital of Hebei Medical University,Shijiazhuang,Hebei,China 050031;School of Pharmacy,Hebei Medical University,Shijiazhuang,Hebei,China 050017)

机构地区：[1]河北医科大学第一医院药学部,河北石家庄050031 [2]河北医科大学药学院,河北石家庄050017

出　　处：《中国药业》2022年第19期51-55,共5页China Pharmaceuticals

基　　金：河北省中医药管理局科研计划项目[Z2022014,2017066]。

摘　　要：目的建立测定大鼠血浆中反式-橙花叔醇质量浓度的液相色谱串联质谱(LC-MS/MS)法,并用于药代动力学(PK)研究。方法大鼠灌胃50 mg/kg反式-橙花叔醇,给药后特定时间点采血,以磺胺甲噁唑为内标,血浆样品采用乙腈沉淀蛋白处理。色谱柱为Synergifusion-RPC_(18)柱(50 mm×3.0 mm,4μm),流动相为乙腈-含0.1%甲酸和1 mmol/L乙酸铵的水溶液(40∶60,V/V),流速为400μL/min。采用电喷雾离子源,正离子模式,多反应监测模式。建立标准曲线,计算血药浓度,根据血药浓度建立血药浓度-时间曲线,并计算主要PK参数。结果含药血浆标准曲线的质量浓度线性范围为0.01~40μg/mL,相关系数(r)为0.9972(n=10);定量下限为0.01μg/mL;反式-橙花叔醇日内精密度试验的RSD≤6.20%,日间精密度试验的RSD≤7.67%;提取回收率≥(91.28±4.94)%。反式-橙花叔醇在大鼠血浆中稳定性良好,主要PK参数峰浓度(C_(max))为(21.38±3.08)μg/mL,半衰期(t_(1/2))为(1.950±0.346)h,0~t药时曲线下面积(AUC_(0-t))为(52.62±10.37)μg/(mL·h),表观分布容积(V_(Z/F))为(2.660±0.333)L/kg,0~t平均驻留时间(MRT_(0-t))为(2.650±0.341)h。结论所建立的LC-MS/MS法准确、可靠,可用于大鼠血浆中反式-橙花叔醇的质量浓度测定及其PK研究。Objective To establish a liquid chromatography-tandem mass spectrometry(LC-MS/MS)method for the determination of trans-nerolidol in plasma of rats,and to provide a reference for the pharmacokinetics(PK)study of trans-nerolidol.Methods The rats were given 50 mg/kg of trans-nerolidol by gavage.Blood samples were collected at specific time points after the administration,and sulfamethoxazole was used as the internal standard.The plasma samples were treated with acetonitrile for precipitation protein.The chromatographic column was Synergi fusion-RP C18 column(50 mm×3.0 mm,4μm),the mobile phase was acetonitrile-aqueous solution containing 0.1%formic acid and 1 mmol/L ammonium acetate(40∶60,V/V),and the flow rate was 400μL/min.The electrospray ion source and multiple reaction monitoring mode were performed in the positive ion mode.A standard curve was established,and the blood concentration was calculated.The blood concentration-time curve was established according to the blood concentration,and the main PK parameters were calculated.Results The linear range of the mass concentration of the standard curve of plasma containing drugs was 0.01-40μg/mL,with the correlation coefficient(r)of 0.9972(n=10).The lower limit of quantification of trans-nerolidol was 0.01μg/mL.The RSD of intra-day precision test of trans-nerolidol≤6.20%,and the RSD of inter-day precision test of trans-nerolidol≤7.67%.The extraction recovery rate of trans-nerolidol≥(91.28±4.94)%.The trans-nerolidol in the plasma of rats was stable,and the main PK parameter peak concentration(C_(max))was(21.38±3.08)μg/mL,half-life(t_(1/2))was(1.950±0.346)h,area under the curve from 0 to t(AUC_(0-t))was(52.62±10.37)μg/(mL•h),apparent distribution volume(V_(Z/F))was(2.660±0.333)L/kg,and mean residence time from 0 to t(MRT_(0-t))was(2.650±0.341)h.Conclusion The established LC-MS/MS method is accurate and reliable,which can be used for the determination of trans-nerolidol in plasma of rats and the study of its PK.

关 键 词：反式-橙花叔醇 液相色谱串联质谱法 药代动力学 大鼠 

分 类 号：R932[医药卫生—生药学] R285.5[医药卫生—药学]