Simultaneous Determination of D and L Enantiomers of 2-Hydroxyglutarate by UHPLC-MS/MS Method in Human Biological Fluids and its Clinical Application.

IF 1.5 4区 化学 Q4 BIOCHEMICAL RESEARCH METHODS
Xiaoqing Li, Yunhai Bo, Le Le, Fen Yang
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引用次数: 0

Abstract

2-hydroxyglutarate has limited abundance in normal tissues but a high level under certain pathologic conditions. To clarify the diagnostic value of two chiral isomers of 2-hydroxyglutarate in plasma and urine of Chinese cancer patients, an ultra-high performance liquid chromatography-tandem mass spectrometric method was developed for simultaneous quantification of D-/L-2-hydroxyglutarate. The selected D-/L-2-hydroxyglutarate-d5 as internal standards were added to samples before the SPE on Waters Oasis® MAX 96-Well plate (30 μm, 60 mg). A derivatization step with (+)-O,O'-diacetyl-L-tartaric anhydride permitted the chromatography separation of D-/L-2-hydroxyglutarate on an ACQUITY UPLC-HSS T3 column (50 × 2.1 mm, i.d. 1.8 μm) with acetonitrile and water (containing 0.1% formic acid and 10 mmol ammonium acetate) as the mobile phase. The calibration curves showed good linearity (R ≥ 0.99) over the concentration ranges of 200-5,000 ng/mL and 500-20,000 ng/mL for analysis of D-/L-2-hydroxyglutarate in plasma and urine samples, respectively. Intra- and inter-run precision were ≤ 12.33%, and the accuracy was within the range of -10.44 to 13.90%. This method was further successfully applied to clinical sample analysis in isocitrate dehydrogenase 1/2 mutated Chinese cancer patients.

超高效液相色谱-质谱/质谱法同时测定人体生物液体中2-羟基戊二酸D和L对映体及其临床应用
2-羟基戊二酸在正常组织中含量有限,但在某些病理情况下含量较高。为明确中国癌症患者血浆和尿液中2-羟基戊二酸两种手性异构体的诊断价值,建立了一种超高效液相色谱-串联质谱法同时定量检测D-/L-2-羟基戊二酸的方法。样品在Waters Oasis® MAX 96孔板(30 μm,60 mg)上进行固相萃取前,先加入选定的D-/L-2-羟基戊二酸-d5作为内标物。用(+)-O,O'-二乙酰基-L-酒石酸酐进行衍生化后,D-/L-2-羟基戊二酸酯在 ACQUITY UPLC-HSS T3 色谱柱(50 × 2.1 mm,内径 1.8 μm)上进行色谱分离,流动相为乙腈和水(含 0.1%甲酸和 10 mmol 乙酸铵)。在血浆和尿液样品中 D-/L-2- 羟基戊二酸的浓度范围分别为 200-5,000 纳克/毫升和 500-20,000 纳克/毫升时,校准曲线显示出良好的线性关系(R ≥ 0.99)。结果表明,D-/L-2-羟基戊二酸在血浆和尿液中的检出限分别为500-20,000 ng/mL和5,000-5,000 ng/mL。该方法成功地应用于异柠檬酸脱氢酶1/2突变的中国癌症患者的临床样本分析。
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来源期刊
CiteScore
2.90
自引率
7.70%
发文量
94
审稿时长
5.6 months
期刊介绍: The Journal of Chromatographic Science is devoted to the dissemination of information concerning all methods of chromatographic analysis. The standard manuscript is a description of recent original research that covers any or all phases of a specific separation problem, principle, or method. Manuscripts which have a high degree of novelty and fundamental significance to the field of separation science are particularly encouraged. It is expected the authors will clearly state in the Introduction how their method compares in some markedly new and improved way to previous published related methods. Analytical performance characteristics of new methods including sensitivity, tested limits of detection or quantification, accuracy, precision, and specificity should be provided. Manuscripts which describe a straightforward extension of a known analytical method or an application to a previously analyzed and/or uncomplicated sample matrix will not normally be reviewed favorably. Manuscripts in which mass spectrometry is the dominant analytical method and chromatography is of marked secondary importance may be declined.
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