一种简单灵敏的梯度洗脱液相色谱串联质谱法用于测定兔血浆中阿霉素的含量

doi:10.5246/jcps.2016.08.064

中国药学(英文版) ›› 2016, Vol. 25 ›› Issue (8): 576-581.DOI: 10.5246/jcps.2016.08.064

一种简单灵敏的梯度洗脱液相色谱串联质谱法用于测定兔血浆中阿霉素的含量

李佳林^1,2, 郭李盈^1,2, 覃小雅^1,2, 范田园^1,2*

1. 北京大学天然药物及仿生药物国家重点实验室, 北京 100191
2. 北京大学药学院分子药剂学与新释药系统北京市重点实验室, 北京 100191

收稿日期:2016-04-21 修回日期:2016-05-10 出版日期:2016-09-01 发布日期:2016-05-15
通讯作者: Tel.: +86-010-82805123, E-mail: tianyuan_fan@bjmu.edu.cn
基金资助:
National Natural Science Foundation of China (Grant No. 81473113).

A simple and sensitive gradient elution liquid chromatography with tandem mass spectrometry (LC-MS/MS) method for the quantification of doxorubicin in rabbit plasma

Jialin Li^1,2, Liying Guo^1,2, Xiaoya Qin^1,2, Tianyuan Fan^1,2*

1. State Key Laboratory of Natural and Biomimetic Drugs, Peking University Health Science Center, Beijing 100191, China
2. Beijing Key Laboratory of Molecular Pharmaceutics and New Drug Delivery Systems, School of Pharmaceutical Sciences, Peking University Health Science Center, Beijing 100191, China

Received:2016-04-21 Revised:2016-05-10 Online:2016-09-01 Published:2016-05-15
Contact: Tel.: +86-010-82805123, E-mail: tianyuan_fan@bjmu.edu.cn
Supported by:
National Natural Science Foundation of China (Grant No. 81473113).

摘要/Abstract

摘要：

本研究建立和验证了测定兔血浆中阿霉素含量的液相色谱串联质谱法(LC-MS/MS)。采用乙酸乙酯萃取血浆样品中的阿霉素和柔红霉素(内标)。以配有C₁₈预柱(2.1 mm×10 mm, 2.5 μm)的C₁₈色谱柱(2.1 mm×50 mm, 2.5 μm)进行色谱分离, 采用0.1%甲酸水溶液–乙腈二元梯度洗脱: 在0-1 min, 1-8 min和8-15 min两者比例分别为82:18-82:18 (v/v), 82:18-50:50 (v/v)和50:50-82:18 (v/v), 流速为0.4 mL/min; 色谱柱柱温设定为40 ^oC, 样品进样量为10 μL。液相流出液使用电喷雾离子源(ESI, 正离子模式), 质谱多反应监测模式检测, 检测离子: 阿霉素m/z 544.07→396.96, 内标: m/z 528.06→321.05。阿霉素在2–600 ng/mL范围内, 线性关系良好, 最低定量限为2 ng/mL。该方法的专属性、基质效应、提取回收率及样品稳定性均符合要求。日内准确度和日间准确度的相对误差范围分别为-2.48%~0.18%和-3.78%~1.94%。日内精密度和日间精密度的相对标准偏差值分别小于8.65%和6.41%。结果显示, 该方法为检测家兔血浆中阿霉素的含量提供了一种可靠的手段。

关键词: 阿霉素, 液相色谱串联质谱, 梯度洗脱, 兔血浆

Abstract:

In the present study, we developed and validated a simple and sensitive gradient elution liquid chromatography tandem mass spectrometry (LC-MS/MS) method for quantification of doxorubicin in rabbit plasma. Daunorubicin was used as an internal standard (IS). The doxorubicin and IS were extracted with ethyl acetate from plasma samples. The chromatographic separations were achieved on a C₁₈column (2.1 mm×50 mm, 2.5 μm) configured with a C₁₈ guard column (2.1 mm×10 mm, 2.5 μm). The mobile phase of 0.1% formic acid-water solution and acetonitrile was delivered using a gradient elution program at a flow rate of 0.4 mL/min. The temperature for column was maintained at 40 ºC. The electrospray ionization (ESI) source was operated in the positive ion mode, and the quantification was conducted using multiple reaction monitoring (MRM) of the transitions m/z 544.07→396.96 and m/z 528.06→321.05 for doxorubicin and IS, respectively. The calibration curve of doxorubicin was linear (r > 0.999) within the range of 2-600 ng/mL. The lower limit of quantification was 2 ng/mL. The relative errors of intraday and inter-day accuracies ranged from -2.48% to 0.18% and from -3.78% to 1.94%, respectively. The relative standard deviations of intraday and inter-day precisions were less than 8.65% and 6.41%, respectively. The method exhibited satisfactory results in terms of specificity, sensitivity, matrix effect, recovery and stability. The newly developed LC-MS/MS method was reliable to monitor doxorubicin concentrations in rabbit plasma.

Key words: Doxorubicin, LC-MS/MS, Gradient elution, Rabbit plasma

中图分类号:

R969.1

Supporting:

李佳林, 郭李盈, 覃小雅, 范田园. 一种简单灵敏的梯度洗脱液相色谱串联质谱法用于测定兔血浆中阿霉素的含量[J]. 中国药学(英文版), 2016, 25(8): 576-581.

Jialin Li, Liying Guo, Xiaoya Qin, Tianyuan Fan. A simple and sensitive gradient elution liquid chromatography with tandem mass spectrometry (LC-MS/MS) method for the quantification of doxorubicin in rabbit plasma[J]. Journal of Chinese Pharmaceutical Sciences, 2016, 25(8): 576-581.

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一种简单灵敏的梯度洗脱液相色谱串联质谱法用于测定兔血浆中阿霉素的含量

A simple and sensitive gradient elution liquid chromatography with tandem mass spectrometry (LC-MS/MS) method for the quantification of doxorubicin in rabbit plasma

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