Rapid and accurate method for quantifying busulfan in plasma samples by isocratic liquid chromatography-tandem mass spectrometry (LC-MS/MS)
Villena-Ortiz, Yolanda (Universitat Autònoma de Barcelona. Departament de Bioquímica i de Biologia Molecular)
Castellote, Laura (Hospital Universitari Vall d'Hebron. Institut de Recerca)
Martínez Sánchez, Luisa María (Universitat Autònoma de Barcelona. Departament de Bioquímica i de Biologia Molecular)
Benítez-Carabante, María I. (Hospital Universitari Vall d'Hebron)
Miarons, Marta (Hospital Universitari Vall d'Hebron. Institut de Recerca)
Vima-Bofarull, Jaume (Hospital Universitari Vall d'Hebron. Institut de Recerca)
Barquin-DelPino, Raquel (Hospital Universitari Vall d'Hebron. Institut de Recerca)
Paciucci, Rosanna (Hospital Universitari Vall d'Hebron. Institut de Recerca)
Rodríguez Frías, Francisco (Universitat Autònoma de Barcelona. Departament de Bioquímica i de Biologia Molecular)
Ferrer Costa, Roser (Hospital Universitari Vall d'Hebron. Institut de Recerca)
Casis-Saez, Ernesto (Hospital Universitari Vall d'Hebron. Institut de Recerca)
López-Hellín, Joan (Hospital Universitari Vall d'Hebron. Institut de Recerca)

Data:	2022
Resum:	Objectives: Administration of busulfan is extending rapidly as a part of a conditioning regimen in patients undergoing hematopoietic stem cell transplantation (HSCT). Monitoring blood plasma levels of busulfan is recommended for identifying the optimal dose in patients and for minimizing toxicity. The aim of this research was to validate a simple, rapid, and cost-effective analytical tool for measuring busulfan in human plasma that would be suitable for routine clinical use. This novel tool was based on liquid chromatography coupled to mass spectrometry. Methods: Human plasma samples were prepared using a one-step protein precipitation protocol. These samples were then resolved by isocratic elution in a C18 column. The mobile phase consisted 2 mM ammonium acetate and 0. 1% formic acid dissolved in a 30:70 ratio of methanol/water. Busulfan-d8 was used as the internal standard. Results: The run time was optimized at 1. 6 min. Standard curves were linear from 0. 03 to 5 mg/L. The coefficient of variation (%CV) was less than 8%. The accuracy of this method had an acceptable bias that fell within 85-115% range. No interference between busulfan and the interfering compound hemoglobin, lipemia, or bilirubin not even at the highest concentrations of compound was tested. Neither carryover nor matrix effects were observed using this method. The area under the plasma drug concentration-time curves obtained for 15 pediatric patients who received busulfan therapy prior to HSCT were analyzed and correlated properly with the administered doses. Conclusions: This method was successfully validated and was found to be robust enough for therapeutic drug monitoring in a clinical setting.
Drets:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Llengua:	Anglès
Document:	Article ; recerca ; Versió publicada
Matèria:	Hematopoietic stem cell transplantation ; Mass spectrometry platform ; Method validation ; Therapeutic drug monitoring
Publicat a:	Advances in Laboratory Medicine, Vol. 3, Issue 3 (September 2022) , p. 263-271, ISSN 2628-491X

DOI: 10.1515/almed-2022-0016
PMID: 37362141

9 p, 534.4 KB

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