Exploring the boundaries of bioanalytical quantitative LC–MS–MS

Lagerwerf, Fija M.; Dongen, W. D. van; Steenvoorden, R.J.J.M.; Honing, Maarten; Jonkman, J. H. G.

doi:10.1016/s0165-9936(00)00009-1

Cited by 64 publications

(45 citation statements)

References 21 publications

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“…However on the second machine, the metabolite did no longer provide a stable assay. A separate assay had to be implemented for this metabolite only [7].…”

Section: Technology Transfermentioning

confidence: 99%

LC-MS-MS experiences with internal standards

2002

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SummaryOver the years of chromatographic evolution, the purpose of using internal standards for quantitative determinations in bioanalysis has shifted from covering (correcting for) random and systematic errors of the entire method (including sample preparation, chromatography and detection) to currently covering (correcting for) random and systematic errors of the detection, by MS-MS especially. However, the need for internal standards in current LC-MS-MS is also dependent on the degree of chromatographic separation and the degree of sample clean-up. This emphasizes the need for integrated method development, including selection of an internal standard. Available options for internal standard selection are (1) no internal standard, (2) a structurally related compound, (3) a structurally similar compound or (4) a stable isotope labelled compound. An overview of the purposes of internal standards in bioanalytical LC-MS-MS is given and this overview is supported by various illustrations using different types of internal standards.An overview of the purposes of internal standards in bioanalytical LC-MS-MS is given. It is supported byvarious illustrations using different b, pes of internal standards.The option of using cleuterated internal standards has given us surprising results in some cases, where chromatographic and/or extraction behaviour of cleuterated internal standards was different from the analyte.

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“…However on the second machine, the metabolite did no longer provide a stable assay. A separate assay had to be implemented for this metabolite only [7].…”

Section: Technology Transfermentioning

confidence: 99%

LC-MS-MS experiences with internal standards

2002

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“…During the process of API, substantial fluctuations in the ionization yield occur over seconds to minutes (18 ). Thus, compared to ultraviolet and fluorescence detection, the stability of the signal in LC-MS/MS is rather poor.…”

Section: Ionization Of Analytesmentioning

confidence: 99%

Pitfalls Associated with the Use of Liquid Chromatography–Tandem Mass Spectrometry in the Clinical Laboratory

2010

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BACKGROUND Novel mass spectrometric techniques such as atmospheric pressure ionization and tandem mass spectrometry have substantially extended the spectrum of clinical chemistry methods during the past decade. In particular, liquid chromatography tandem–mass spectrometry (LC-MS/MS) has become a standard tool in research laboratories as well as in many clinical laboratories. Although LC-MS/MS has features that suggest it has a very high analytical accuracy, potential sources of inaccuracy have recently been identified. CONTENT The sources of inaccuracy in LC-MS/MS methods used in the routine quantification of small molecules are described and discussed. Inaccuracy of LC-MS/MS methods can be related to the process of ionization through the insource transformation of conjugate metabolites or target analytes and may also be attributable to ionization matrix effects that have a differential impact on target analytes and internal-standard compounds. Inaccuracy can also be associated with the process of ion selection, which mainly occurs when compounds from the sample matrix share mass transitions with a target analyte. In individual assays, most potential sources of inaccuracy can be controlled by sufficient LC separation–based sample workup before MS analysis. SUMMARY LC-MS/MS methods should undergo rigorous and systematic validation before introduction into patient care.

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“…For example, if a drug and a glucuronide metabolite were quantified by IS against a close analogue of the parent drug and matrix effects were slightly different between samples, then the change in ionization of the more polar glucuronide metabolite would probably not be compensated by the IS. Thus if there are multiple analytes to be quantified, with varying degrees of polarity, there may be requirements for multiple IS (Lagerwerf et al, 2000). The importance of matrix effects on the reliability of HPLC-ESI-MS/MS has been shown in terms of accuracy and precision (Matuszewski et al, 1998), and when ion suppression occurs, the sensitivity and lower limit of quantification of a method may be adversely affected (Buhrman et al, 1996).…”

Section: What Is the Matrix Effect?mentioning

confidence: 99%

Principles and Applications of LC-MS/MS for the Quantitative Bioanalysis of Analytes in Various Biological Samples

Kang¹

2012

Tandem Mass Spectrometry - Applications and Principles

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Exploring the boundaries of bioanalytical quantitative LC–MS–MS

Cited by 64 publications

References 21 publications

LC-MS-MS experiences with internal standards

LC-MS-MS experiences with internal standards

Pitfalls Associated with the Use of Liquid Chromatography–Tandem Mass Spectrometry in the Clinical Laboratory

Principles and Applications of LC-MS/MS for the Quantitative Bioanalysis of Analytes in Various Biological Samples

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