Quantification of clofarabine and fludarabine in plasma by high-performance liquid chromatography-tandem mass spectrometry Journal Article
| Authors: | Schofield, R. C.; Scordo, M.; Shah, G.; Carlow, D. C. |
| Article Title: | Quantification of clofarabine and fludarabine in plasma by high-performance liquid chromatography-tandem mass spectrometry |
| Abstract: | Allogeneic hematopoietic cell transplantation (allo-HCT) is a potentially curative therapeutic treatment for many patients with high-risk hematologic malignancies and bone marrow failure syndromes. While allo-HCT can be highly effective, it is met with significant bone marrow conditioning regimen-related toxicities and complications such as infections related to poor immune reconstitution. This chapter describes the measurement of clofarabine and fludarabine concentrations to support clinical trials whose goal is to determine the optimal therapeutic ranges in order to maximize effectiveness while minimizing variability and regimen-related adverse events and toxicities. Moreover, the same holds true for patients receiving fludarabine as part of their lymphodepleting chemotherapy for chimeric antigen receptor T-cells (CAR T-cells). It is believed that one of the causes of variable outcomes after CAR T-cell therapy is lymphodepletion due to the variable fludarabine concentrations. This chapter describes a HPLC-MS/MS method to measure both compounds simultaneously. Clofarabine and fludarabine are extracted with solvent from plasma by the addition of deuterated internal standards prepared in methanol. Chromatographic separation is attained using a reversed-phase column followed by mass spectrometry which is performed in the positive ion mode. Herein, the described method to quantify both compounds in plasma is fast, accurate, and sensitive and allows for rapid drug concentration monitoring and timely dose adjustments. © 2024, The Author(s), under exclusive license to Springer Science+Business Media, LLC, part of Springer Nature. |
| Keywords: | controlled study; fludarabine; mass spectrometry; chemistry; tandem mass spectrometry; drug blood level; high performance liquid chromatography; chromatography, high pressure liquid; plasma; clofarabine; particle size; vidarabine; pharmacokinetics; procedures; limit of quantitation; humans; human; method validation; high-performance liquid chromatography |
| Journal Title: | Methods in Molecular Biology |
| Volume: | 2737 |
| ISSN: | 1064-3745 |
| Publisher: | Humana Press Inc |
| Date Published: | 2024-01-01 |
| Start Page: | 175 |
| End Page: | 184 |
| Language: | English |
| DOI: | 10.1007/978-1-0716-3541-4_17 |
| PROVIDER: | scopus |
| PUBMED: | 38036821 |
| DOI/URL: | |
| Notes: | Chapter 17 in "Clinical Applications of Mass Spectrometry in Drug Analysis. 2nd Ed" (ISBN: 978-1-0716-3540-7) -- The MSK Cancer Center Support Grant (P30 CA008748) is acknowledged in the PDF -- Doesn't list a corresponding author -- Source: Scopus |
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