Measurement of the DNA alkylating agents busulfan and melphalan in human plasma by mass spectrometry Journal Article
| Authors: | Schofield, R. C.; Landau, H. J.; Giralt, S. A.; Shah, G. L.; Scordo, M.; Lin, A.; Zanutto, E.; Ramanathan, L. V.; Pessin, M. S.; Carlow, D. C. |
| Article Title: | Measurement of the DNA alkylating agents busulfan and melphalan in human plasma by mass spectrometry |
| Abstract: | Busulfan and melphalan are cytotoxic DNA alkylating agents that are used in many hematopoietic stem cell transplantation (HCT) conditioning regimens. We report the development of an assay using turbulent flow liquid chromatography (TFLC) and tandem mass spectrometry to simultaneously measure the concentration of busulfan (Bu) and melphalan (Mel) in human plasma. The method involves precipitating proteins in the plasma specimen with an organic solvent containing deuterated internal standards of both compounds. Following centrifugation, an aliquot of the supernatant was injected into the TFLC mass spectrometry system operated in the positive ion mode. The analytical measurement range for both compounds was 10–5000 ng/mL, and with validated dilutions the reportable range was extended to 25,000 ng/mL. Intra-day and inter-day (n = 20 day) precision studies showed a coefficient of variation (CV) of <7% at several concentrations across the measurement range. To determine accuracy recovery studies were performed at several concentrations spanning the measurement range. Recoveries for both compounds were between 98 and 103%. Additionally, busulfan was compared with an existing assay and showed excellent correlation. Experiments were conducted to rule out matrix effects, carryover and interference from endogenous substances. The validated clinically reportable range (CRR) and assay precision will allow this assay to be used clinically to monitor and adjust Mel and Bu levels to ensure better therapeutic outcomes and also to support clinical trials aimed at better defining therapeutic ranges. © 2019 Elsevier B.V. |
| Keywords: | busulfan; mass spectrometry; melphalan; hematopoietic stem cell transplantation; stem cells; tandem mass spectrometry; turbulent flow; liquid chromatography; mutagens; positive ions; turbulent flow liquid chromatography; pharmacokinetic studies; plasma (human); endogenous substances; spectrometry systems; therapeutic outcomes |
| Journal Title: | Journal of Chromatography B-Analytical Technologies in the Biomedical and Life Sciences |
| Volume: | 1125 |
| ISSN: | 1570-0232 |
| Publisher: | Elsevier Science BV |
| Date Published: | 2019-09-01 |
| Start Page: | 121711 |
| Language: | English |
| DOI: | 10.1016/j.jchromb.2019.121711 |
| PUBMED: | 31376591 |
| PROVIDER: | scopus |
| PMCID: | PMC6692901 |
| DOI/URL: | |
| Notes: | Article -- Export Date: 4 September 2019 -- Source: Scopus |
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