LC–MS/MS method development for quantification of busulfan in human plasma and its application in pharmacokinetic study

Nadella, Taraka Ramarao; Vidyadhara, S.; Lankapalli, Sasidhar R; Mandava, Venkata Basaveswara Rao; Bandarupalli, Deepti

doi:10.1016/j.jpba.2015.12.024

Cited by 12 publications

(3 citation statements)

References 4 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…More recently, methodologies based on liquid chromatography coupled with tandem mass spectrometry (HPLC-MS/MS) have been developed that result in high analytical specificity and sensitivity, significantly shorter turnaround times, and a simplified workflow. [10][11][12][13][14][15][16][17][18][19] Minimizing run times is important during TDM to facilitate timely decision-making regarding treatment changes; however, a detailed evaluation of interfering compounds is mandatory. Recently, Villena-Ortiz et al 7 investigated the possible interference (%) between Bu and hemoglobin, lipemia, and bilirubin.…”

Section: Introductionmentioning

confidence: 99%

PEG 400 Ion Suppression in Busulfan Detection by High-Performance Liquid Chromatography—Tandem Mass Spectrometry

De Gregori,

Capone,

De Silvestri

et al. 2023

Therapeutic Drug Monitoring

View full text Add to dashboard Cite

Background: Busulfan (Bu), an alkylating agent commonly used in chemotherapy and transplantation, exhibits high intraindividual pharmacokinetic variability and possible time-dependent variations in clearance, which complicate therapeutic drug monitoring. Numerous analytical methods have been developed to reduce analysis time and facilitate timely decision-making regarding treatment changes; however, the validation procedures rarely involve analysis of potentially interfering excipients. Macrogol 400 (PEG 400) should be considered as a possible interfering agent in the detection of plasma Bu levels, especially as an ionization suppressor. Methods: Six intravenous formulations of Bu were compared with identify at least 1 common excipient (PEG 400). During the 176 therapeutic drug monitoring analyses of Bu, one of the PEG 400 specific mass-to-charge ratio transitions was determined using an instrumental method. After coelution with Bu and its internal standard (Bu-d8) was confirmed, all analyses were repeated using a different experimental setup free of ion suppression induced by PEG. The concentration–time profile of PEG 400 was also analyzed. Results: The area under the curve obtained from the 2 data sets was compared and analyzed using Lin concordance correlation coefficient and Bland–Altman plot analysis. The results from the 2 analytical methods were comparable: PEG 400 negatively affected the Bu-d8 coefficient of variation but not the Bu/Bu-d8 ratio. Conclusions: The possible interference of PEG 400 should be thoroughly investigated, especially with respect to analytical methods that cannot be supported by correction of the stable isotopically labeled internal standard analog.

show abstract

Section: Introductionmentioning

confidence: 99%

PEG 400 Ion Suppression in Busulfan Detection by High-Performance Liquid Chromatography—Tandem Mass Spectrometry

De Gregori,

Capone,

De Silvestri

et al. 2023

Therapeutic Drug Monitoring

View full text Add to dashboard Cite

show abstract

“…Some of the chromatographic assays have been reported for quantification of Bu in biological fluids. The methods comprise high performance liquid chromatographic assays (HPLC) [18][19][20] , liquid chromatographic-mass spectrometric (LC-MS) 21,22 and tandem mass spectrometric (LC-MS/MS) assay methods [23][24][25][26][27][28][29][30][31][32] . There are some limitations pertaining to the reported HPLC assay methods which include complications such as tedious, arduous and time-consuming sample extraction procedures.…”

mentioning

confidence: 99%

“…Other reported methods utilized drugs such as glipizide (anti-diabetic medication) as an internal standard, which may potentially lead to under-estimation of Bu levels in patient's sample containing Bu and glipizide 24 . The other disadvantages of the reported methods include lack of reliability since they did not assess the potential matrix effect (ME) [21][22][23][29][30][31][32] . Evaluation of ME in LC-MS or LC-MS/MS bioanalytical methods is essential since it may affect the precision and accuracy of the bioanalytical methods and therefore, any data elicited from a method where ME was not assessed may not be thrust-worthy.…”

mentioning

confidence: 99%

UPLC-Tandem Mass Spectrometry for Quantification of Busulfan in Human Plasma: Application to Therapeutic Drug Monitoring

Matar

Alshemmari

Refaat

et al. 2020

Sci Rep

View full text Add to dashboard Cite

Busulfan (Bu) is an alkylating agent commonly used in preparative regimens for hematologic malignant and non-malignant patients undergoing hematopoietic stem cell transplantation (HSCT). The objective of the present study was to develop an UPLC-MS/MS method for quantification of Bu in human plasma. A total of 55 patients with hematologic malignancies (n = 34) and non-malignancies (n = 21) received myeloablative Bu therapy prior to HSCT. A tandem mass spectrometric method was developed and validated to quantify Bu levels in these patients. The method was fully validated over the concentration range of 25-2000 ng/mL (r > 0.99). The assay method demonstrated good precision and accuracy. Stability studies indicated that the drug was stable in various conditions. Incurred sample reanalysis findings were within acceptable ranges (<15% of the nominal concentration). Based on the 1 st dose AUC results, one third of hematologic malignant patients and half of non-malignant patients needed dose adjustment. However, in subsequent doses (5 th , 9 th , and 13 th), 77%, 82% and 82%, respectively, of hematologic malignant patients and 71%, 67% and 86%, respectively, of non-malignant patients achieved the target range of Bu AUC. The suitability of the developed method for routine TDM of Bu in HSCT patients was demonstrated. The study suggests that the pharmacokinetic profile of Bu varies in both groups.

show abstract

A rapid and simple LC–MS/MS method for personalized busulfan dosing in pediatric patients undergoing hematopoietic stem cell transplantation (HSCT)

Xiao

2018

Clinica Chimica Acta

View full text Add to dashboard Cite

LC–MS/MS method development for quantification of busulfan in human plasma and its application in pharmacokinetic study

Cited by 12 publications

References 4 publications

PEG 400 Ion Suppression in Busulfan Detection by High-Performance Liquid Chromatography—Tandem Mass Spectrometry

PEG 400 Ion Suppression in Busulfan Detection by High-Performance Liquid Chromatography—Tandem Mass Spectrometry

UPLC-Tandem Mass Spectrometry for Quantification of Busulfan in Human Plasma: Application to Therapeutic Drug Monitoring

A rapid and simple LC–MS/MS method for personalized busulfan dosing in pediatric patients undergoing hematopoietic stem cell transplantation (HSCT)

Contact Info

Product

Resources

About