Simultaneous quantitation of hydroxychloroquine and its metabolites in mouse blood and tissues using LC-ESI-MS/MS: An application for pharmacokinetic studies.
Simultaneous quantitation of hydroxychloroquine and its metabolites in mouse blood and tissues using LC-ESI-MS/MS: An application for pharmacokinetic studies.
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使用LC-ESI-MS/MS同时定量小鼠血液和组织中其代谢产物的定量：药代动力学研究的应用。
DOI：
10.1016/j.jchromb.2017.11.026
复制
发表时间：
2018-01-01
期刊：
影响因子：
--
通讯作者：
Murry DJ
中科院分区：
文献类型：
--
作者：
Chhonker YS;Sleightholm RL;Li J;Oupický D;Murry DJ
羟氯喹（HCQ）已被证明可以破坏自噬，并使癌细胞对放射和化疗药物敏感。然而，这些效果所需的最佳递送方法、剂量和肿瘤浓度尚不清楚。这在一定程度上是由于缺乏灵敏且可重复的小动物HCQ定量分析方法。因此，我们开发并验证了一种选择性和灵敏的液相色谱-串联质谱（LC-MS/MS）方法，用于同时定量羟氯喹及其代谢产物在小鼠血液和组织中。采用Thermo Aquasil C18（50 × 4.6 mm，3μ）色谱柱，以0.2%甲酸和0.1%甲酸的甲醇溶液为移动的相，梯度洗脱，流速为0.5 mL/min，蛋白质沉淀法提取。分析物分离和定量使用MS/MS与电喷雾电离源在正多反应监测（MRM）模式。对于所有分析物，MS/MS响应在1-2000 ng/mL浓度范围内呈线性，相关系数（R2）为0.998或更好。根据FDA指南，日内和日间精密度（相对标准偏差，% RSD）和准确度在可接受限度内。经验证的方法已成功应用于临床前药代动力学小鼠研究，涉及低体积的血液和组织样本的羟氯喹和代谢产物。
Hydroxychloroquine (HCQ) has been shown to disrupt autophagy and sensitize cancer cells to radiation and chemotherapeutic agents. However, the optimal delivery method, dose, and tumor concentrations required for these effects are not known. This is in part due to a lack of sensitive and reproducible analytical methods for HCQ quantitation in small animals. As such, we developed and validated a selective and sensitive liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS) method for simultaneous quantitation of hydroxychloroquine and its metabolites in mouse blood and tissues. The chromatographic separation and detection of analytes were achieved on a reversed phase Thermo Aquasil C18 (50 × 4.6 mm, 3μ) column, with gradient elution using 0.2 % formic acid and 0.1% formic acid in methanol as mobile phase at a flow rate of 0.5 mL/min. Simple protein precipitation was utilized for extraction of analytes from the desired matrix. Analytes were separated and quantitated using MS/MS with an electrospray ionization source in positive multiple reaction monitoring (MRM) mode. The MS/MS response was linear over the concentration range from 1–2000 ng/mL for all analytes with a correlation coefficient (R2) of 0.998 or better. The within- and between-day precision (relative standard deviation, % RSD) and accuracy were within the acceptable limits per FDA guidelines. The validated method was successfully applied to a preclinical pharmacokinetic mouse study involving low volume blood and tissue samples for hydroxychloroquine and metabolites.
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DOI：
10.1016/j.jpba.2014.07.009
发表时间：
2014-11-01
影响因子：
3.4
作者：
Soichot, Marion;Megarbane, Bruno;Bourgogne, Emmanuel
通讯作者：
Bourgogne, Emmanuel
影响因子：
--
作者：
Costedoat-Chalumeau, Nathalie;Amoura, Zahir;Piette, Jean-Charles
通讯作者：
Piette, Jean-Charles
DOI：
10.1016/s0378-4347(00)82024-1
发表时间：
1985-01-01
期刊：
JOURNAL OF CHROMATOGRAPHY
影响因子：
--
作者：
TETT, SE;CUTLER, DJ;BROWN, KF
通讯作者：
BROWN, KF
影响因子：
3.8
作者：
Fan, Hong-wei;Ma, Zhi-xiang;Li, Ying-bin
通讯作者：
Li, Ying-bin
影响因子：
5
作者：
Fuezery, Anna K.;Breaud, Autumn R.;Clarke, William A.
通讯作者：
Clarke, William A.