Ultra high performance liquid chromatographic-tandem mass spectrometric multi-analyte approach for target screening and quantification in human blood plasma : development, validation, and application

摘要

In the presented studies, the development of an UHPLC-MS/MS approach for fast target screening and quantification in plasma was described. This approach covered 136 analytes out of the drug classes of antidepressants, neuroleptics, benzodiazepines, beta-blockers, oral antidiabetics, and analytes to be determined in the context of brain death diagnosis. Further, it was possible to find one chromatographic system with the same column and mobile phase compositions to separate almost all these analytes sufficiently. A fast and simple liquid-liquid extraction for all these analytes was developed. In addition, the presented studies showed that ion suppression and enhancement tests were essential, particularly for the selection of internal standards for UHPLC-MS/MS multi-analyte procedures and for combining co-eluting analytes during method validation. Furthermore, this approach was fully validated for the most important drug classes of antidepressants, neuroleptics, and benzodiazepines. This approach was valid for 28 antidepressants, 24 neuroleptics, and 21 benzodiazepines. In addition, the applicability was shown successfully using authentic human blood samples and external quality control samples. The cost and time saving one-point calibration was shown to be sufficient for more than half of the analytes.