Simultaneous Determination of 6-Mercaptopurine and its Oxidative Metabolites in Synthetic Solutions and Human Plasma using Spectrophotometric Multivariate Calibration Methods.

BioImpacts : BI Pub Date : 2011-01-01 Epub Date: 2011-06-09 DOI:10.5681/bi.2011.008
Mohammad-Hossein Sorouraddin, Mohammad-Yaser Khani, Kaveh Amini, Abdolhossein Naseri, Davoud Asgari, Mohammad-Reza Rashidi
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引用次数: 15

Abstract

Introduction: 6-Mercaptopurine (6MP) is an important chemotherapeutic drug in the conventional treatment of childhood acute lymphoblastic leukemia (ALL). It is catabolized to 6-thiouric acid (6TUA) through 8-hydroxo-6-mercaptopurine (8OH6MP) or 6-thioxanthine (6TX) intermediates.

Methods: High-performance liquid chromatography (HPLC) is usually used to determine the contents of therapeutic drugs, metabolites and other important biomedical analytes in biological samples. In the present study, the multivariate calibration methods, partial least squares (PLS-1) and principle component regression (PCR) have been developed and validated for the simultaneous determination of 6MP and its oxidative metabolites (6TUA, 8OH6MP and 6TX) without analyte separation in spiked human plasma. Mixtures of 6MP, 8-8OH6MP, 6TX and 6TUA have been resolved by PLS-1 and PCR to their UV spectra.

Results: Recoveries (%) obtained for 6MP, 8-8OH6MP, 6TX and 6TUA were 94.5-97.5, 96.6-103.3, 95.1-96.9 and 93.4-95.8, respectively, using PLS-1 and 96.7-101.3, 96.2-98.8, 95.8-103.3 and 94.3-106.1, respectively, using PCR. The NAS (Net analyte signal) concept was used to calculate multivariate analytical figures of merit such as limit of detection (LOD), selectivity and sensitivity. The limit of detections for 6MP, 8-8OH6MP, 6TX and 6TUA were calculated to be 0.734, 0.439, 0.797 and 0.482 μmol L-1, respectively, using PLS and 0.724, 0.418, 0783 and 0.535 μmol L-1, respectively, using PCR. HPLC was also applied as a validation method for simultaneous determination of these thiopurines in the synthetic solutions and human plasma.

Conclusion: Combination of spectroscopic techniques and chemometric methods (PLS and PCR) has provided a simple but powerful method for simultaneous analysis of multicomponent mixtures.

分光光度多变量校准法同时测定合成液和人血浆中6-巯基嘌呤及其氧化代谢物
简介:6-巯基嘌呤(6MP)是儿童急性淋巴细胞白血病(ALL)常规治疗中的重要化疗药物。它通过8-羟基-6-巯基嘌呤(8OH6MP)或6-硫黄嘌呤(6TX)中间体分解代谢为6-硫脲酸(6TUA)。方法:常用高效液相色谱法测定生物样品中治疗药物、代谢物等重要生物医学分析物的含量。在本研究中,建立了多元校准方法、偏最小二乘法(PLS-1)和主成分回归(PCR),并验证了在不分离分析物的情况下同时测定人血浆中6MP及其氧化代谢物(6TUA、8OH6MP和6TX)。6MP, 8-8OH6MP, 6TX和6TUA的混合物通过PLS-1和PCR对其紫外光谱进行分辨。结果:6MP、8-8OH6MP、6TX和6TUA的回收率(%)分别为94.5-97.5、96.6-103.3、95.1-96.9和93.4-95.8,PCR法分别为96.7-101.3、96.2-98.8、95.8-103.3和94.3-106.1。NAS(净分析物信号)的概念被用于计算多变量分析值的优点,如检出限(LOD),选择性和灵敏度。PLS法计算6MP、8-8OH6MP、6TX和6TUA的检出限分别为0.734、0.439、0.797和0.482 μmol L-1; PCR法计算6MP、8-8OH6MP、6TX和6TUA的检出限分别为0.724、0.418、0783和0.535 μmol L-1。采用高效液相色谱法同时测定合成溶液和人血浆中这些硫嘌呤的含量。结论:光谱技术与化学计量学方法(PLS和PCR)的结合为多组分混合物的同时分析提供了一种简单而有效的方法。
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