Abstract
N,N′,N′′-Triethylenethiophosphoramide (thioTEPA) is a polyfunctional, organophosphorus alkylating agent that has been a primary treatment of multiple solid malignancies for many years and more recently as part of conditioning regimens prior to hematopoietic stem cell transplantation for a variety of hematologic malignancies. In vivo, thioTEPA is quickly metabolized to N,N′,N″-triethylenephosphoramide (TEPA). ThioTEPA and TEPA have similar alkylating activity and both exhibit outstanding central nervous system penetration. Therefore, it is possible and desirable to monitor both compounds in plasma and cerebrospinal fluid (CSF).
This chapter describes a method to measure both compounds simultaneously. ThioTEPA and TEPA are extracted with solvent from plasma and CSF by the addition of deuterated internal standards prepared in methanol. Chromatographic separation is attained using a C18 column and mass spectrometry which is performed in the positive ion mode. Herein, we describe a fast, accurate, and sensitive assay to quantify both compounds in plasma and CSF by turbulent flow LC-MS/MS which allows for fast and accurate therapeutic drug monitoring and timely dose modifications.
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Acknowledgments
This work was supported by the Department of Pathology and Laboratory Medicine of Memorial Sloan Kettering Cancer Center and through the NIH/NCI Cancer Center Support Grant P30 CA008748.
Conflict of Interest RCS, DCC report no conflicts. MS served as a paid consultant for McKinsey & Company, Angiocrine Bioscience, Inc., and Omeros Corporation; received research funding from Angiocrine Bioscience, Inc., Omeros Corporation, and Amgen, Inc.; served on ad hoc advisory boards for Kite – A Gilead Company; and received honoraria from i3Health, Medscape, and CancerNetwork for CME-related activity. GS reports research funding from Janssen, Amgen, BMS, Beyond Spring, and GPCR Therapeutics and DSMB for ArcellX.
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Schofield, R.C., Scordo, M., Shah, G., Carlow, D.C. (2024). Measurement of ThioTEPA and Its Metabolite TEPA in Plasma and Cerebrospinal Fluid by Turbulent Flow Chromatography-Tandem Mass Spectrometry. In: Garg, U. (eds) Clinical Applications of Mass Spectrometry in Drug Analysis. Methods in Molecular Biology, vol 2737. Humana, New York, NY. https://doi.org/10.1007/978-1-0716-3541-4_39
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DOI: https://doi.org/10.1007/978-1-0716-3541-4_39
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