Kamal M. Matar
Kuwait University, Kuwait
Title: Therapeutic Drug Monitoring of Busulfan by UPLC-Tandem Mass Spectrometry
Biography
Biography: Kamal M. Matar
Abstract
Background: Busulfan (Bu) is an alkylating agent commonly used in preparative regimens for patients undergoing
hematopoietic stem cell transplantation (HSCT) for various types of malignancies. A rapid, selective, reliable, precise, accurate,
and reproducible method for quantifi cation of Bu in human plasma using Acquity UPLC system coupled to triple quadrupole
tandem mass detector (TQD) has been developed and validated to be used routinely for TDM of Bu employing Busulfan-d8
as an internal standard (IS).
Methods: Th e drug and IS were extracted by ether and analyzed on Acquity UPLC BEH C18 column (2.1x50 mm, 1.7 μm).
Quantitation was achieved using positive electrospray ion source (ESI+) interface employing MRM mode.
Results: Th e method was validated over the concentration range of 25–2000 ng/ml (r>0.99). Intra- and inter-run precision of
Bu assay at four concentrations (50, 500, 1250 and 1750 ng/ml) ranged from 1.2 to 6.5% with accuracy (bias) varied from –10.7
to –0.2% indicating good precision and accuracy. Stability of Bu in human plasma samples at diff erent conditions showed that
the drug was stable under the studied conditions.
Conclusion: Th e suitability of the developed method for routine TDM was demonstrated by measuring Bu in human plasma
samples of patients under preparative and conditioning regimens who will undergo hematopoietic cell transplantation (HCT)
for various malignancies including acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) as well as nonmalignancy
conditions such as thalassemias.