用UPLC-MS/MS法测定大鼠血浆中索格列净的浓度  

Determination of sotagliflozin in rat plasma by UPLC-MS/MS method

作　　者：曹格溪 张晓旭[3] 邓艳茹 闫彬 董占军[2,4] CAO Ge-xi;ZHANG Xiao-xu;DENG Yan-ru;YAN Bin;DONG Zhan-jun(Graduate School,Hebei Medical University,Shijiazhuang 050051,Hebei Province,China;Department of Pharmacy,Hebei General Hospital,Shijiazhuang 050051,Hebei Province,China;Department of Acupuncture and Moxibustion,Hebei General Hospital,Shijiazhuang 050051,Hebei Province,China;Hebei Key Laboratory of Clinical Pharmacy,Hebei General Hospital,Shijiazhuang 050051,Hebei Province,China)

机构地区：[1]河北医科大学研究生学院,河北石家庄050051 [2]河北省人民医院药学部,河北石家庄050051 [3]河北省人民医院针灸科,河北石家庄050051 [4]河北省人民医院河北省临床药学重点实验室,河北石家庄050051

出　　处：《中国临床药理学杂志》2025年第2期230-234,共5页The Chinese Journal of Clinical Pharmacology

基　　金：河北省自然科学基金资助项目(H2022307063);河北省医学科学研究课题资助项目(20211721)。

摘　　要：目的建立高效液相色谱串联质谱(UPLC-MS/MS)法,测定大鼠血浆中索格列净浓度,并应用于大鼠体内的药代动力学研究。方法电喷雾负离子方式多反应离子检测;色谱柱:EXT-C_(18)柱(2.1mm×100.0mm,2.7μm);柱温:45℃;流动相:含5mmol·L^(-1)乙酸铵水-乙腈;流速:0.35mL·min^(-1);索格列净离子对:m/z483.3→315.1达格列净离子对:m/z467.4→329.2;进样量:6μL,用甲基叔丁基醚液液萃取法处理血浆样品。将6只SD雄性大鼠单次灌胃索格列净40mg·kg^(-1),检测血浆中索格列净的浓度,用DrugAnd Statistics(DAS)2.1.1软件计算药代动力学参数。结果索格列净在5~2000ng·mL^(-1)内线性关系良好,日内和日间精密度均小于15%,回收率、基质效应与稳定性均在规定范围;药代动力学参数:C_(max)为(3716.67±568.28)ng·mL^(-1),t_(max)为(1.00±0.32)h,t_(1/2)为(2.28±0.45)h,AUC_(0-t)为(1.70×10^(4)±2075.87)ng·mL^(-1)·h。结论本研究建立了大鼠血浆中索格列净浓度的测定方法,具有灵敏度高、检测快速、重复性良好等特点,适用于血浆中索格列净浓度测定及药代动力学等研究。Objective To establish a ultra-high performance liquid chromatography-tandem mass spectrometer(UPLC-MS/MS)method for determining the concentration of sotagliflozin in rat plasma and apply it to pharmacokinetic studies in rats.MethodssElectrospray negative ion multi-reaction ion detection was used.Chromatographic column:EXT-C_(18)(2.1 mm×100.0 mm,2.7μm);column temperature:45℃;mobile phase:5 mmol:L^(-1)ammonium acetate aqueous solution-acetonitrile;flow rate:0.35 mL·min^(-1);ion pairs:sotagliflozin m/z 483.3→315.1,dapagliflozin m/z 467.4→329.2;injection volume:6μL,plasma samples were processed using methyl tert-butyl ether liquid-liquid extraction.Six male SD rats were administered a single oral dose of sogliflozin at 40 mg·kg^(-1),and detected the concentration of sogliflozin in plasma.Pharmacokinetic parameters were calculated using Drug And Statistics(DAS)2.1.1.ResultssSotagliflozin showed good linearity within the range of 5-2000 ng·mL^(-1),with intra-day and inter-day precision both less than 15%.The recovery rate,matrix effect,and stability were all within the specified range.Pharmacokinetic parameters:C_(max)was(3716.67±568.28)ng·mL^(-1),tm wasmax(1.00±0.32)h,t_(1/2)was(2.28±0.45)h,AUC_(0-t)was(1.70×10±2075.87)ng·mL^(-1).h.Conclusion This study established a method for determining the concentration of sotagliflozin in rat plasma,which is characterized by high sensitivity,rapid detection,and good repeatability.It is suitable for the determination of sotagliflozin concentration in plasma and pharmacokinetic studies.

关 键 词：索格列净 血药浓度 药代动力学 超高效液相色谱-质谱联用法 

分 类 号：R977.15[医药卫生—药品]