A novel method for quantitation of acylglycines in human dried blood spots by UPLC-tandem mass spectrometry
Autor: | Lawrence Fisher, Nathalie Lepage, Herman J. ten Brink, Christine Davies, Osama Y. Al-Dirbashi, Pranesh Chakraborty |
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Přispěvatelé: | Clinical chemistry, AGEM - Endocrinology, metabolism and nutrition, AGEM - Inborn errors of metabolism, NCA - Brain mechanisms in health and disease |
Jazyk: | angličtina |
Rok vydání: | 2018 |
Předmět: |
Male
0301 basic medicine Resolution (mass spectrometry) Clinical Biochemistry Glycine Ion suppression in liquid chromatography–mass spectrometry Urine Tandem mass spectrometry High-performance liquid chromatography 03 medical and health sciences 0302 clinical medicine Tandem Mass Spectrometry 030225 pediatrics medicine Humans Chromatography High Pressure Liquid Newborn screening Chromatography Chemistry Infant Newborn General Medicine MCADD medicine.disease 030104 developmental biology Female Dried Blood Spot Testing False positive rate Metabolism Inborn Errors |
Zdroj: | Clinical Biochemistry, 54, 131-138. Elsevier Inc. Fisher, L, Davies, C, Al-Dirbashi, O Y, ten Brink, H J, Chakraborty, P & Lepage, N 2018, ' A novel method for quantitation of acylglycines in human dried blood spots by UPLC-tandem mass spectrometry ', Clinical Biochemistry, vol. 54, pp. 131-138 . https://doi.org/10.1016/j.clinbiochem.2018.01.020 |
ISSN: | 0009-9120 |
Popis: | Background Several acylcarnitines used as primary markers on dried blood filter papers (DBS) for newborn screening lack specificity and contribute to a higher false positive rate. The analysis of urine acylglycines is useful in the diagnosis of inborn errors of metabolism (IEM) including medium chain acyl-CoA dehydrogenase deficiency (MCADD), isovaleric acidemia, and beta-ketothiolase deficiency (BKTD). Currently, no method for analyzing acylglycines from DBS has been published. Methods Acylglycines were extracted from two 3.2 mm DBS punches and butylated using Butanol-HCl. Ultra Performance Liquid Chromatography (UPLC-MS/MS) with run time of 10 min permits resolution and quantitation of 15 acylglycines; including several isobaric. Method development was completed. Reference intervals (n = 573) were established for four birth weight groups. Furthermore, samples from patients with a confirmed IEM (n = 11), and false positive screens (n = 78) were analyzed to validate the interpretation obtained from the newly established reference intervals. Results Calibration curves were linear from 0.005 to 25.0 μM. Ion suppression was evaluated as minimal (2 to 10%). Samples from known patients were used to validate the reference intervals. For C5OH-related disorders, tiglylglycine (TG), TG/acetylglycine (AG) ratio, 3methylcrotonylglycine (3MCG) and 3MCG/AG ratio increased specificity. Propionylglycine (PG) and PG/acetylglycine ratio were two discriminatory markers in the investigation of C3-related disorders. Hexanoylglycine (HG), octanoylglycine (OG), suberylglycine (SG), and the ratios HG/AG, OC/AG and SG/AG were excellent markers of MCADD deficiency. Conclusion This method shows potential application as a second tier screen in order to reduce the false positive rate for a number of IEM targeted by newborn screening. |
Databáze: | OpenAIRE |
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