摘要
建立LC-MS/MS测定Beagle犬血浆中地文拉法辛的方法,研究多规格琥珀酸地文拉法辛缓释片的药动学。使用安捷伦Extend-C18(4.6 mm×150 mm,5μm)色谱柱,柱温为室温,流动相为10.0 mmol/L乙酸铵水溶液(含0.2%的甲酸)(A)-甲醇(B),流速为1.0 mL·min-1。采用电喷雾离子源(ESI+)结合多重反应检测模式(MRM)进行检测,地文拉法辛、内标(O-地文拉法辛-d10)的检测离子对分别为m/z 264.3→58.1、m/z 274.3→58.1。方法学研究显示,Beagle犬血浆中地文拉法辛的线性范围为0.500~500 ng·mL^(-1)(r=0.9982,定量下限为0.500 ng·mL^(-1)),质控样品批内精密度CV≤6.64%,批间精密度CV≤4.99%,准确度相对偏差为-8.00%~8.89%,地文拉法辛在多种条件下稳定性结果RSD均<15.0%。建立的检测方法灵敏、操作步骤简单、科学可靠,适用于比格犬血浆中地文拉法辛的检测。
To establish a LC-MS/MS method for the determination of the concentrations of desvenlafaxine in Beagle dogs plasma and to study the pharmacokinetics of desvenlafaxine succinate sustained-release tablets(50 mg&100 mg).Agilent Extend-C 18(4.6 mm×150 mm,5μm)column was used with the mobile phase consisting of 10.0 mM Ammonium acetate aqueous solution(containing 0.2%formic acid)(A)and methanol(B).The flow rate was controlled at 1.0 mL·min-1 with the column temperature was set at room temperature.Electrospray positive ionization source(ESI+)combined with multiple reaction monitoring mode was selected,with quantitative transition m/z 264.3→58.1 for desvenlafaxine,and m/z 274.3→58.1 for internal standard(O-desvenlafaxine-d 10).Methodological studies showed that the the linear range of desvenlafaxine in Beagle dogs plasma were 0.500~500 ng·mL^(-1)(r=0.9982,lower limit of quantification was 0.500 ng·mL^(-1)).The inter-batch and intra-batch precision CVs of quality-control samples were less than 6.64%and 4.99%,respectively.The accuracy were in the range of-8.00%~8.89%in terms of relative error.The stability results of desvenlafaxine under various experimental conditions showed that all RSD were<15.0%.The method is sensitive,convenient,reliable and suitable for determination of desvenlafaxine in Beagle dogs plasma.
作者
毛杰
顾阳
薛留亮
吴青青
孙春艳
宣景安
田凤杰
刘显琦
吕慧敏
MAO Jie;GU Yang;XUE Liuliang;WU Qingqing;SUN Chunyan;XUAN Jing′an;TIAN Fengjie;LIU Xianqi;LYU Huimin(National Key Laboratory of Complex Drug Formulations for Overcoming Delivery Barriers,Yangtze River Pharmaceutical(Group)Co.,Ltd.,Taizhou 225300,China;Beijing Union-Genius Pharmaceutical Technology Ltd.,Beijing 100176,China)
出处
《山东化工》
CAS
2024年第19期173-176,共4页
Shandong Chemical Industry
