Very complex internal standard response variation in LC-MS/MS bioanalysis: Root cause analysis and impact assessment

Van De Merbel, N. C., Koster, R. A. & Ohnmacht, C., 27-Nov-2019, In : Bioanalysis. 11, 18, p. 1693-1700 8 p.

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  • Very complex internal standard response variation in LC–MS-MS bioanalysis root cause analysis and impact assessment

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Internal standards (ISs) are essential for the development and use of reliable quantitative bioanalytical LC-MS/MS methods, because they correct for fluctuations in the analytical response that are caused by variations in experimental conditions. Sample-to-sample differences in the IS response are thus to be expected, but a large variability often is an indication of nonoptimal sample handling or analysis settings. This paper discusses a number of cases of very complex variation of IS responses that could be attributed to analytical problems such as injection errors and sample inhomogeneity, and matrix-related issues such as degradation and increased ionization efficiency. A decision tree is proposed to help find the underlying root cause for extreme IS variability.
Original languageEnglish
Pages (from-to)1693-1700
Number of pages8
Issue number18
Publication statusPublished - 27-Nov-2019


  • internal standard, LC-MS, matrix effects, response variability, root cause analysis, decision tree, ionization, liquid chromatography-mass spectrometry, matrix effect, review, standard, SPECTROMETRY

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