Generic DART-MS platform for monitoring the on-demand continuous-flow production of pharmaceuticals: Advancing the quantitative protocol for caffeates in microfluidic biocatalysis

文献类型: 外文期刊

第一作者: Xu, Yan

作者: Xu, Yan;Zhang, Dong-Yang;Liu, Xi;Sheng, Sheng;Wu, Guo-Hua;Wang, Jun;Wu, Fu-An;Xu, Yan;Zhang, Dong-Yang;Sheng, Sheng;Wu, Guo-Hua;Wang, Jun;Wu, Fu-An;Meng, Xiang-Yun

作者机构:

关键词: Caffeates;Caffeic acid phenethyl ester;Continuous-flow synthesis;Direct analysis in real time mass;spectrometry;Methyl caffeate;Microfluidic biocatalysis

期刊名称:JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS ( 影响因子:3.935; 五年影响因子:3.563 )

ISSN:

年卷期:

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收录情况: SCI

摘要: Today, continuous processing is regarded as an effective on-demand production technique of pharmaceuticals. Homemade microreactors packed with immobilized lipase under continuous-flow conditions were first applied to tailor the production of high-value caffeic add phenethyl ester (CAPE) from methyl caffeate (MC) and 2-phenylethanol (PE) in cyclohexane via transesterification; however, this method is challenging due to the lack of a rapid platform for monitoring caffeates in microfluidic biocatalysis. The reactants were directly analyzed using Direct Analysis in Real Time Mass Spectrometry (DART-MS), and the corresponding ionization parameters were investigated. Special ions produced from MC (parent ion m/z 192.87 and product ion m/z 133.44) and CAPE (parent ion m/z 282.93 and product ion m/z 178.87) were determined using DART-MS2 in the negative ion mode. The peak areas of the select reaction monitoring (SRM) signals were calculated to develop the standard curves for quantitative analyses of the concentration. Reasonable linear regression equations of MC and CAPE were obtained in the range of 3.125-50.000 mg/L, with linear coefficients (R-2) of 0.9515 and 0.9973, limits of detection (LOD) of 0.005 and 0.003 mg/L, limits of quantification (LOQ) of 0.02 and 0.01 mg/L, and recovery ranges of 92.50-97.11% and 90.11-97.60%, respectively. The results using DART-MS2 were in good agreement with those using conventional High-Performance Liquid Chromatography with a UV detector (HPLC-UV) and were successfully applied to monitor the kinetics constants and mass transfer coefficients in a continuous-flow packed bed microreactor. Thus, the DART-MS2 method is an efficient tool for analyzing caffeates in microfluidic biocatalysis with limited sample preparation and short operating time. (C) 2017 Elsevier B.V. All rights reserved.

分类号: R9

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