Simultaneous and enantiospecific quantification of primaquine and carboxyprimaquine in human plasma using liquid chromatography-tandem mass spectrometry.
Simultaneous and enantiospecific quantification of primaquine and carboxyprimaquine in human plasma using liquid chromatography-tandem mass spectrometry.
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DOI：
10.1186/s12936-022-04191-w
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发表时间：
2022-06-03
期刊：
影响因子：
3
通讯作者：
Tarning, Joel
中科院分区：
文献类型：
--
作者：
Hanpithakpong, Warunee;Day, Nicholas P. J.;White, Nicholas J.;Tarning, Joel
8-氨基喹啉抗疟药伯氨喹的对映体具有不同的药理学性质。开发一种同时定量测定伯氨喹及其代谢物羧基伯氨喹对映体的分析方法，将支持临床药物计量学评估。建立了液相色谱-串联质谱联用（LC-MS /MS）同时测定人血浆中伯氨喹及其代谢产物羧基伯氨喹对映体特异性的方法。用稳定同位素作为内标来补偿潜在的干扰和基质效应。血浆样品（100µL）用1%甲酸在乙腈中沉淀，然后进行磷脂去除固相萃取。在Chiralcel OD-3R （150 mm × 4.6 mm, id 3 μm）柱上采用LC梯度模式分离伯氨喹和羧基伯氨喹对映体。采用反相色谱柱（Hypersil Gold 100 mm × 4.6 mm； id为3µm），流动相为10 mm醋酸铵缓冲液，pH为3.5，乙腈为等密度模式，对液相色谱法进行了改进和验证。方法验证按照法规要求进行。伯氨喹和羧基伯氨喹对映体的校准范围分别为0.571 ~ 260 ng/mL和2.44 ~ 2500 ng/mL，所有校准曲线的相关系数（r2）均≥0.0998。伯氨喹和羧基伯氨喹对映体的日内、日间测定精密度< 10%，准确度在94.7% ~ 103%之间。对映体特异性方法也进行了改进和验证，以定量外消旋型伯氨喹和羧基伯氨喹，将总运行时间从30分钟减少到8分钟。外消旋定量方法的日内、日间测定精密度< 15%。伯氨喹和羧基伯氨喹的绝对回收率在70% ~ 80%之间。在- 80°C条件下稳定性可达2年。对映体和外消旋LC-MS /MS方法均成功应用于健康志愿者的药代动力学研究。建立了简便、灵敏、准确的LC-MS /MS定量人血浆中对映体和外消旋体伯氨喹和羧基伯氨喹的方法，并成功应用于临床常规药物分析。
The enantiomers of the 8-aminoquinoline anti-malarial primaquine have different pharmacological properties. Development of an analytical method for simultaneous quantification of the enantiomers of primaquine and its metabolite, carboxyprimaquine, will support clinical pharmacometric assessments. A simple and sensitive method consisting of liquid chromatography coupled with tandem mass spectrometry (LC–MS/MS) was developed for simultaneous and enantiospecific determination of primaquine and its metabolite, carboxyprimaquine, in human plasma. Stable isotopes were used as internal standards to compensate for potential interference and matrix effects. Plasma samples (100 µL) were precipitated with 1% formic acid in acetonitrile followed by phospholipid removal solid phase extraction. Primaquine and carboxyprimaquine enantiomers were separated on a Chiralcel OD-3R (150 mm × 4.6 mm; I.D. 3 μm) column using a LC gradient mode. For separation of racemic primaquine and carboxyprimaquine, the LC method was modified and validated using a reverse phase column (Hypersil Gold 100 mm × 4.6 mm; I.D. 3 µm) and a mobile phase composed of 10 mM ammonium acetate buffer, pH 3.5 and acetonitrile in the isocratic mode. Method validation was performed according to regulatory guidelines. The calibration range was set to 0.571–260 ng/mL and 2.44–2,500 ng/mL for primaquine and carboxyprimaquine enantiomers, respectively, resulting in a correlation coefficient (r2) ≥ 0.0998 for all calibration curves. The intra- and inter-day assay precisions were < 10% and the accuracy was between 94.7 to 103% for all enantiomers of primaquine and carboxyprimaquine. The enantiospecific method was also modified and validated to quantify racemic primaquine and carboxyprimaquine, reducing the total run time from 30 to 8 min. The inter-, intra-day assay precision of the racemic quantification method was < 15%. The absolute recoveries of primaquine and carboxyprimaquine were between 70 and 80%. Stability was demonstrated for up to 2 years in − 80 °C. Both the enantiomeric and racemic LC–MS/MS methods were successfully implemented in pharmacokinetic studies in healthy volunteers. Simple, sensitive and accurate LC–MS/MS methods for the quantification of enantiomeric and racemic primaquine and carboxyprimaquine in human plasma were validated successfully and implemented in clinical routine drug analysis.
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影响因子：
4.9
作者：
Hanboonkunupakarn, Borimas;Ashley, Elizabeth A.;White, Nicholas J.
通讯作者：
White, Nicholas J.
DOI：
10.1016/s1570-0232(02)00142-3
发表时间：
2002-06-15
影响因子：
3
作者：
Müller, C;Schäfer, P;Weinmann, W
通讯作者：
Weinmann, W
影响因子：
4.9
作者：
Lourens, Chris;Lindegardh, Niklas;Tarning, Joel
通讯作者：
Tarning, Joel
DOI：
10.1093/jac/dky297
发表时间：
2018-11-01
期刊：
The Journal of antimicrobial chemotherapy
影响因子：
--
作者：
Chairat K;Jittamala P;Hanboonkunupakarn B;Pukrittayakamee S;Hanpithakpong W;Blessborn D;White NJ;Day NPJ;Tarning J
通讯作者：
Tarning J
DOI：
10.1016/0378-4347(92)80370-6
发表时间：
1992-08-07
期刊：
JOURNAL OF CHROMATOGRAPHY-BIOMEDICAL APPLICATIONS
影响因子：
--
作者：
ENDOH, YS;YOSHIMURA, H;NISHIKAWA, M
通讯作者：
NISHIKAWA, M