Validation of a liquid chromatography-tandem mass spectrometry method for simultaneous quantification of N,N-dimethylacetamide and N-monomethylacetamide in pediatric plasma.

Autor: Rosser SPA; The Children's Hospital at Westmead Clinical School, University of Sydney, Sydney, Australia.; Department of Biochemistry, The Children's Hospital at Westmead, Sydney, Australia.; Cancer Centre for Children, The Children's Hospital at Westmead, Sydney, Australia., McLachlan AJ; Sydney Pharmacy School, Faculty of Medicine and Health, University of Sydney, Sydney, Australia., Hempel G; Institute for Pharmaceutical and Medicinal Chemistry and Clinical Pharmacy, University of Münster, Sydney, Germany., Chung J; The Children's Hospital at Westmead Clinical School, University of Sydney, Sydney, Australia.; Department of Biochemistry, The Children's Hospital at Westmead, Sydney, Australia., Shaw PJ; The Children's Hospital at Westmead Clinical School, University of Sydney, Sydney, Australia.; Cancer Centre for Children, The Children's Hospital at Westmead, Sydney, Australia., Keogh SJ; Cancer Centre for Children, The Children's Hospital at Westmead, Sydney, Australia., Nath CE; Department of Biochemistry, The Children's Hospital at Westmead, Sydney, Australia.; Cancer Centre for Children, The Children's Hospital at Westmead, Sydney, Australia.; Sydney Pharmacy School, Faculty of Medicine and Health, University of Sydney, Sydney, Australia.
Jazyk: angličtina
Zdroj: Journal of separation science [J Sep Sci] 2023 May; Vol. 46 (10), pp. e2201003. Date of Electronic Publication: 2023 Mar 15.
DOI: 10.1002/jssc.202201003
Abstrakt: N,N-dimethylacetamide is an excipient used in intravenous busulfan formulations, a drug used in hematopoietic stem cell transplantation conditioning. The aim of this study was to develop and validate a liquid chromatography-tandem mass spectrometry method for simultaneous quantification of N,N-dimethylacetamide, and its metabolite N-monomethylacetamide in plasma from children receiving busulfan. A 4 μl aliquot of patient plasma was extracted using 196 μl 50% methanol solution and quantified against calibrators prepared in the extraction solvent given negligible matrix effects across three concentrations. 9 [H 2 ]-N,N-dimethylacetamide was used as an internal standard. Separation of N,N-dimethylacetamide and N-monomethylacetamide was achieved using a Kinetex EVO C18 stationary phase (100 mm × 2.1 mm × 2.6 μm) running an isocratic mobile phase of 30% methanol containing 0.1% formic acid at a flow of 0.2 ml/min over 3.0 min. The injection volume was 1 μl. Calibration curves for N,N-dimethylacetamide and N-monomethylacetamide were linear up to 1200 and 200 μg/L, respectively, with a lower limit of quantification 1 μg/L for both analytes. Calibrator accuracy and precision were within ± 10% of the test parameters across four concentration levels. Analytes were stable over 14 days at three different storage conditions. This method was successfully applied to measure N,N-dimethylacetamide and N-monomethylacetamide concentrations in a total of 1265 plasma samples from 77 children.
(© 2023 The Authors. Journal of Separation Science published by Wiley-VCH GmbH.)
Databáze: MEDLINE
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