Abstract
Busulfan is an alkylating agent and functions as a myeloablative and anti-leukemic chemotherapy drug. It is widely used with cyclophosphamide for conditioning patients undergoing bone marrow transplantation for myeloid leukemia. Studies have shown that the busulfan plasma concentration correlates better with clinical efficacy and toxicity than the patient’s administered dosage. Low concentrations predispose to disease recurrence and even graft rejection, and higher concentrations can increase the risk of hepatic toxicity. As a result, dosing levels can vary significantly from patient to patient. Therapeutic drug monitoring (TDM) of busulfan plasma concentration guides the dosage adjustment to optimally achieve complete bone marrow ablation while minimizing the dosage-dependent toxicity. The quick and precise (precision <10%) UPLC-MS/MS method described here for monitoring plasma busulfan levels between 50 ng/mL and 5000 ng/mL involves the addition of an organic solvent and deuterated internal standard (busulfan d-8) followed by a liquid-liquid extraction, injection of the extract onto a C18 column, and analysis by multiple reaction monitoring (MRM) in ESI-positive mode.
This is a preview of subscription content, log in via an institution to check access.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
Cavo M, Bandini G, Benni M, Gozzetti A, Ronconi S, Rosti G, Zamagni E, Lemoli RM, Bonini A, Belardinelli A, Motta MR, Rizzi S, Tura S (1998) High-dose busulfan and cyclophosphamide are an effective conditioning regimen for allogeneic bone marrow transplantation in chemosensitive multiple myeloma. Bone Marrow Transplant 22(1):27–32
O’Donnell MR, Long GD, Parker PM, Niland J, Nademanee A, Amylon M, Chao N, Negrin RS, Schmidt GM, Slovak ML et al (1995) Busulfan/cyclophosphamide as conditioning regimen for allogeneic bone marrow transplantation for myelodysplasia. J Clin Oncol 13(12):2973–2979
Shah AJ, Lenarsky C, Kapoor N, Crooks GM, Kohn DB, Parkman R, Epport K, Wilson K, Weinberg K (2004) Busulfan and cyclophosphamide as a conditioning regimen for pediatric acute lymphoblastic leukemia patients undergoing bone marrow transplantation. J Pediatr Hematol Oncol 26(2):91–97
Slattery JT, Risler LJ (1998) Therapeutic monitoring of busulfan in hematopoietic stem cell transplantation. Ther Drug Monit 20(5):543–549
Verougstraete N, Stove V, Verstraete AG, Oyaert M (2022) Automation in busulfan therapeutic drug monitoring: evaluation of an immunoassay on two routine chemistry analyzers. Ther Drug Monit 44(2):335–339
Hilaire MR, Gill RV, Courtney JB, Baburina I, Gardiner J, Milone MC, Shaw LM, Meng QH, Salamone SJ (2021) Evaluation of a nanoparticle-based busulfan immunoassay for rapid analysis on routine clinical analyzers. Ther Drug Monit 43(6):766–771
Athanasiadou I, Angelis YS, Lyris E, Archontaki H, Georgakopoulos C, Valsami G (2014) Gas chromatographic-mass spectrometric quantitation of busulfan in human plasma for therapeutic drug monitoring: a new on-line derivatization procedure for the conversion of busulfan to 1,4-diiodobutane. J Pharm Biomed Anal 90:207–214
Hassan M, Ehrsson H (1983) Gas chromatographic determination of busulfan in plasma with electron-capture detection. J Chromatogr 277:374–380
Lai WK, Pang CP, Law LK, Wong R, Li CK, Yuen PM (1998) Routine analysis of plasma busulfan by gas chromatography-mass fragmentography. Clin Chem 44(12):2506–2510
Pablo A, Breaud AR, Clarke W (2020) Analysis of busulfan in plasma by liquid chromatography-tandem mass spectrometry (LC-MS/MS). Curr Protoc Toxicol 84(1):e93
Lee EJ, Park N, Lee SH, Lee W, Kim HS, Chun S, Min WK (2019) A simple and accurate liquid chromatography-tandem mass spectrometry method for therapeutic drug monitoring of busulfan in plasma. Ann Clin Lab Sci 49(2):212–217
Deng S, Kiscoan M, Frazee C, Abdel-Rahman S, Dalal J, Garg U (2016) A simple liquid chromatography tandem mass spectrometry method for quantitation of plasma Busulfan. Methods Mol Biol 1383:79–87
Moon SY, Lim MK, Hong S, Jeon Y, Han M, Song SH, Lim KS, Yu KS, Jang IJ, Lee JW, Kang HJ, Song J (2014) Quantification of human plasma-busulfan concentration by liquid chromatography-tandem mass spectrometry. Ann Lab Med 34(1):7–14
French D, Sujishi KK, Long-Boyle JR, Ritchie JC (2014) Development and validation of a liquid chromatography-tandem mass spectrometry assay to quantify plasma busulfan. Ther Drug Monit 36(2):169–174
Vassal G, Re M, Gouyette A (1988) Gas chromatographic-mass spectrometric assay for busulfan in biological fluids using a deuterated internal standard. J Chromatogr 428(2):357–361
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2024 The Author(s), under exclusive license to Springer Science+Business Media, LLC, part of Springer Nature
About this protocol
Cite this protocol
Garg, U., Munar, A., Clinton Frazee, C. (2024). Liquid Chromatography-Tandem Mass Spectrometry Method for the Quantification of Plasma Busulfan. 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_13
Download citation
DOI: https://doi.org/10.1007/978-1-0716-3541-4_13
Published:
Publisher Name: Humana, New York, NY
Print ISBN: 978-1-0716-3540-7
Online ISBN: 978-1-0716-3541-4
eBook Packages: Springer Protocols