Matrix effects on accurate mass measurements of low-molecular weight compounds using liquid chromatography-electrospray-quadrupole time-of-flight mass spectrometry

• Published in: Journal of mass spectrometry 2006-03, Vol.41 (3), p.289-294
• Main Authors: Calbiani, F., Careri, M., Elviri, L., Mangia, A., Zagnoni, I.
• Format: Article
• Language: English
• Subjects: accurate mass measurement; Analytical chemistry; Analytical, structural and metabolic biochemistry; Biological and medical sciences; Calibration; Chemistry; Chromatographic methods and physical methods associated with chromatography; Chromatography, Liquid - methods; Chromatography, Liquid - standards; Exact sciences and technology; Fundamental and applied biological sciences. Psychology; Histamine - analysis; Histamine - blood; Histamine - chemistry; Investigative techniques, diagnostic techniques (general aspects); limit of detection; matrix effect; Medical sciences; Miscellaneous. Technology; Molecular Weight; Non peptidic neurotransmitters, polyamines; Other biological molecules; Other chromatographic methods; Pathology. Cytology. Biochemistry. Spectrometry. Miscellaneous investigative techniques; Pharmaceutical Preparations - chemistry; Phenethylamines - analysis; Phenethylamines - blood; Phenethylamines - chemistry; quadrupole-time-of-flight analyzer; Reproducibility of Results; Spectrometry, Mass, Electrospray Ionization - methods; Spectrometry, Mass, Electrospray Ionization - standards; uncertainty
• ISSN: 1076-5174; 1096-9888
• DOI: 10.1002/jms.984

Liquid chromatography (LC) with high‐resolution mass spectrometry (HRMS) represents a powerful technique for the identification and/or confirmation of small molecules, i.e. drugs, metabolites or contaminants, in different matrices. However, reliability of analyte identification by HRMS is being challenged by the uncertainty that affects the exact mass measurement. This parameter, characterized by accuracy and precision, is influenced by sample matrix and interferent compounds so that questions about how to develop and validate reliable LC‐HRMS‐based methods are being raised. Experimental approaches for studying the effects of various key factors influencing mass accuracy on low‐molecular weight compounds (MW < 150 Da) when using a quadrupole‐time‐of‐flight (QTOF) mass analyzer were described. Biogenic amines in human plasma were considered for the purpose and the effects of peak shape, ion abundance, resolution and data processing on accurate mass measurements of the analytes were evaluated. In addition, the influence of the matrix on the uncertainty associated with their identification and quantitation is discussed. A critical evaluation on the calculation of the limits of detection was carried out, considering the uncertainty associated with exact mass measurement of HRMS‐based methods. The minimum concentration level of the analytes that was able to provide a statistical error lower than 5 ppm in terms of precision was 10 times higher than those calculated with S/N = 3, thus suggesting the importance of considering both components of exact mass measurement uncertainty in the evaluation of the limit of detection. Copyright © 2006 John Wiley & Sons, Ltd.