PDF《urinary excretion study》

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1330 ・ 药学学报 Acta Pharmaceutica Sinica 2015,

50 (10):

1330 ?1335 LC-MS/MS 法同时测定人尿液中苦杏仁苷和芍药苷及其尿药排泄研究 李晓冰

1 , 石富国

2 , 菅凌燕 1* , 丁黎2* (1.

中国医科大学附属盛京医院药学部, 辽宁 沈阳 110004;

2. 中国药科大学药物分析教研室, 江苏 南京 210009) 摘要: 建立苦杏仁苷和芍药苷尿药浓度的 LC-MS/MS 同时测定方法, 研究健康中国受试者静脉滴注活血通 络粉针剂后其体内苦杏仁苷和芍药苷的人体尿药排泄特征.尿液样品经甲醇沉淀蛋白并稀释后, 采用 Hedera ODS-2 色谱柱分离, 流动相为乙腈?5 mmol・L?1 醋酸铵水溶液 (含0.05% 甲酸) (20∶80);

质谱采用 Turbo-Ionspray 电喷雾离子源和正离子多反应监测方式.尿液中杂质不干扰样品的测定, 苦杏仁苷和芍药苷的标准曲线线性范 围为 0.03~40 μg・mL?1 , 线性关系良好;

高、中、低三种浓度的日间和日内精密度均小于 15.0%;

无介质效应、残 留效应;

稳定性良好.9 名健康受试者单次静脉输注活血通络粉针

6 g 后, 苦杏仁苷和芍药苷主要以原形经尿液 排出体外, 平均累计排泄率分别为 79.6% 和48.4%.建立的 LC-MS/MS 分析方法适用于健康中国受试者体内苦 杏仁苷和芍药苷的尿药排泄研究. 关键词: 苦杏仁苷;

芍药苷;

尿药排泄;

LC-MS/MS 中图分类号: R917 文献标识码: A 文章编号: 0513-4870 (2015) 10-1330-06 An LC-MS/MS method for the simultaneous determination of amygdalin and paeoniflorin in human urine and application to urinary excretion study LI Xiao-bing1 , SHI Fu-guo2 , JIAN Ling-yan1* , DING Li2* (1. Department of Pharmacy, Shengjing Hospital of China Medical University, Shenyang 110004, China;

2. Department of Pharmaceutical Analysis, China Pharmaceutical University, Nanjing 210009, China ) Abstract: The study aims to develop an LC-MS/MS method for the simultaneous determination of amygdalin and paeoniflorin in urine samples, and to investigate their urinary excretion characteristics in healthy volunteers after intravenous infusion administration of Huoxue-Tongluo lyophilized powder for injection (HTLPI). The urine samples were extracted by methanol, and then separated on a Hedera ODS-2 column with a mobile phase of acetonitrile and

5 mmol・L?1 ammonium acetate buffer solution containing 0.05% formic acid (20∶80). Electrospray ionization source was applied and operated in the positive ion mode using MRM. The method exhibited good linearity over the concentration range of 0.03 ?40 μg・mL?1 . The values on both the occasions (intra- and inter-day) were all within 15% at three concentration levels. No matrix effect and carry-over effect were observed. Amygdalin and paeoniflorin were stable in human urine under different storage conditions. Approximately 79.6% of the administered amount of amygdalin was excreted unchanged in urine within

24 h and which was 48.4% for paeoniflorin. The developed LC-MS/MS method can be applied to evaluate the urinary excretion of amygdalin and paeoniflorin. Key words: amygdalin;

paeoniflorin;

urinary excretion;

LC-MS/MS 收稿日期: 2015-02-25;

修回日期: 2015-03-26. 基金项目: 国家自然科学基金资助项目 (81273482, 81503169). *通讯作者 Tel / Fax: 86-24-96615-71101, E-mail: [email protected];

Tel / Fax: 86-25-83271289, E-mail: [email protected] 李晓冰等: LC-MS/MS 法同时测定人尿液中苦杏仁苷和芍药苷及其尿药排泄研究 ・