Discussions on the inaccuracy problems and preventing strategies associated with the use of liquid chro-matography-tandem mass spectrometry in quantitative assay of biosamples / 中国药学杂志

ABSTRACT

Liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS) is a widely used technique in the quantitative analysis of small molecules, part of peptides and proteins in biological matrix. When compared with LC, the LC-MS/MS posesses many advantages, such as high sample throughput, high sensitivity and resolutions, simple method development and simultaneous quantification of multiple components. At the stage of method development, the main practices for analysts are to validate analytical methods according to the regulated requirements. However, due to the quantitative mechanisms of LC-MS/MS, even though the used method is fully validated, analytical inaccuracy problem, which is the so called bioanalytical risk (pitfalls), may still exist, if we do not pay attentions to some details. In the present paper, the factors which may cause inaccuracy in quantitative analysis are summarized, especially those could not be found during routine method validation. Those factors include back transformation of unstable drug metabolites to analyte in the handling of biosamples, matrix effects, in-source conversion, and ion interference caused by ions with similar or same mass-to-charge ratio, etc. In addition to QA/QC oversight and strict method validation, the preventing strategies may contain the follows selecting biosample processing method with high proficiency in eliminating matrix interferences, enhancing chromatographic separation, selection of suitable precursor-product ions and validation with incurred samples, etc.