Determination of busulfan in human plasma using high-performance liquid chromatography with pre-column derivatization and fluorescence detection

Peris, José-Esteban; Latorre, José-Antonio; Castel, Victoria; Verdeguer, Amparo; Esteve, Sara; Torres‐Molina, Francisca

doi:10.1016/s0378-4347(99)00214-5

Cited by 35 publications

(14 citation statements)

References 17 publications

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“…28 Busulfan plasma concentrations from Lyon were measured by HPLC with UV detection for data before 2010, 29 and by an updated, cross-validated liquid chromatography – tandem mass spectrometry method after 2010. 30 All the assays used were linear from 20 to 2000 ng/mL with an interday imprecision of <10%.…”

Section: Methodsmentioning

confidence: 99%

Accurately Achieving Target Busulfan Exposure in Children and Adolescents With Very Limited Sampling and the BestDose Software

Neely

Philippe

Rushing

et al. 2016

Therapeutic Drug Monitoring

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Background Busulfan dose adjustment is routinely guided by plasma concentration monitoring using 4–9 blood samples per dose adjustment, but a pharmacometric Bayesian approach could reduce this sample burden. Methods The authors developed a non-parametric population model with Pmetrics. They used it to simulate optimal initial busulfan dosages, and in a blinded fashion, they compared dosage adjustments using the model in the BestDose™ software to dosage adjustments calculated by non-compartmental estimation of AUC at a national reference laboratory in a cohort of patients not included in model building. Results Mean (range) age of the 53 model-building subjects was 7.8 (0.2 – 19.0) years and weight was 26.5 (5.6 – 78.0) kg, similar to nearly 120 validation subjects. There were 16.7 (6 – 26) samples per subject to build the model. The BestDose cohort was also diverse: 10.2 (0.25 – 18) years and 46.4 (5.2 – 110.9) kg. Mean bias and imprecision of the one-compartment model-predicted busulfan concentrations were 0.42% and 9.2%, and were similar in the validation cohorts. Initial dosages to achieve average concentrations of 600–900 ng/mL were 1.1 mg/kg (≤12kg, 67% in the target range and 1.0 mg/kg (>12 kg, 76% in the target range). Using all 9 concentrations after dose 1 in the Bayesian estimation of dose requirements, the mean (95% CI) bias of BestDose calculations for the third dose was 0.2% (−2.4% to 2.9%, P=0.85), compared with the standard non-compartmental method based on 9 concentrations. With one optimally timed concentration 15 minutes after the infusion (calculated with the authors’ novel MMopt algorithm) bias was −9.2% (−16.7% to −1.5%, P=0.02). With two concentrations at 15 minutes and 4 hours bias was only 1.9% (−0.3% to 4.2%, P=0.08). Conclusions BestDose accurately calculates busulfan intravenous dosage requirements to achieve target plasma exposures in children up to 18 years of age and 110 kg using only two blood samples per adjustment compared to 6 – 9 samples for standard non-compartmental dose calculations.

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Section: Methodsmentioning

confidence: 99%

Accurately Achieving Target Busulfan Exposure in Children and Adolescents With Very Limited Sampling and the BestDose Software

Neely

Philippe

Rushing

et al. 2016

Therapeutic Drug Monitoring

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“…LC-MS/MS is the most preferred method for measuring busulfan in a pediatric setting because of its benefits over other methods. GC-based methods and LC-fluorescence/UV techniques are time-consuming and laborious, requiring derivatization steps for preparation and a large quantity of plasma of up to 1 mL, along with a long analysis time of up to 30 min per run [10-13]. The recently developed ELISA-based automated method shows similar precision, required time, and sample volume compared with previously described methods, while having the risk of cross-reactivity and lot-to-lot variability of reagents [14].…”

Section: Discussionmentioning

confidence: 99%

“…Gas chromatography (GC) coupled with electron capture detector [10] or mass spectrometry (MS) [11], liquid chromatography (LC) coupled with UV detectors [12] or fluorescence detectors [13] have been introduced, and an ELISA-based automated method was developed recently [14]. Among the existing methods, LC coupled with MS [15, 16] or with tandem MS (MS/MS) [17, 18] offers a high level of sensitivity and requires a small sample volume, which is beneficial in a pediatric setting.…”

Section: Introductionmentioning

confidence: 99%

Quantification of Human Plasma-Busulfan Concentration by Liquid Chromatography-Tandem Mass Spectrometry

et al. 2014

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BackgroundBusulfan, an alkylating agent administered prior to hematopoietic stem cell transplantation, has a narrow therapeutic range and wide variability in metabolism. We developed a liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for rapid and accurate quantification of plasma busulfan.MethodsBusulfan was separated and detected using an LC system containing a C18 column equipped with MS/MS. The sample was eluted with a mobile phase gradient for a total run time of 10 min. Plasma busulfan concentration was quantified against a 6-point standard curve in a multiple reaction monitoring mode at mass-to-charge (m/z) 264.1 > 151.1. Precision, recovery, matrix effect, linearity, detection capability, carryover, and stability were evaluated. The range of plasma busulfan concentration was obtained by analyzing samples from 9 children receiving busulfan.ResultsThe coefficients of variation of within-run and within-laboratory precision were all below 5%. Recoveries were all within the range of 100-105%. Linearity was verified from 0 to 5,000 ng/mL. Limit of detection and limit of quantification were 1.56 and 25 ng/mL, respectively. Carryover rate was within allowable limits. Plasma busulfan concentration was stable for 2 weeks at -20℃ and -80℃, but decreased by 25% when the plasma was stored for 24 hr at room temperature, and by <5% in 24 hr at 4℃. The plasma busulfan concentrations were between 347 ng/mL and 5,076 ng/mL.ConclusionsOur method using LC-MS/MS enables highly accurate, reproducible, and rapid busulfan monitoring with minimal sample preparation. The method may also enable safe and proper dosage.

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“…Different analytical methods have been developed for busulfan measurement in plasma and other biological fluids, including GC and GC-MS [4][5][6][7], HPLC with UV detection [8][9][10], and with fluorescence detection [11,12] and LC-MS [13,14]. In the present study, we compared two published methods: (1) a rapid and accurate LC-MS assay with SIM mode, (2) a sensitive HPLC-FL assay using 2-naphthalenethiol derivatization for the busulfan quantitation.…”

Section: Introductionmentioning

confidence: 99%

Comparison of LC-MS Assay and HPLC Assay of Busulfan in Clinical Pharmacokinetics Studies

Lin¹,

Goodin²,

Strair³

et al. 2012

ISRN Analytical Chemistry

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Busulfan is used in preparative regimens for bone marrow transplantation and timely busulfan plasma concentration reporting is critical for subsequent dose adjustment. We compared two sensitive methods for pharmacokinetics studies including LC-MS assay and HPLC precolumn derivatization assay. Chromatographic separation was performed on a Gemini C18column. Liquid-liquid extraction with ethyl acetate was used for plasma sample preparation. Busulfan and internal standard ([2H8]-busulfan) were detected as ammonium adducts at m/z 264.2 and 272.2 for LC-MS assay. For HPLC assay, the extraction from plasma was derivatized with 2-naphathalenethiol using synthesized internal standard (1,6-(methanesulfonyloxy)octane). The Ex and Em wavelength was 255 nm and 370 nm. The limit of detection was 15.6 ng/mL and 7.8 ng/mL for HPLC and LC-MS assay and good linearity ranging from 31.25–1000 ng/mL for HPLC and 15.6-1000 ng/mL for LC-MS assay. The intra and interday assay precision were less than 9.2% and 12.0% for LC-MS and HPLC assay. The pharmacokinetic parameters were estimated using noncompartmental pharmacokinetic model with WinNonlin. Busulfan AUClast showed an average difference of 0.7% between the two methods. The LC-MS method is accurate, reproducible, and requires less specimen, sample preparation and analysis time over the HPLC assay, making busulfan monitoring faster and easier in clinical practice.

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Determination of busulfan in human plasma using high-performance liquid chromatography with pre-column derivatization and fluorescence detection

Cited by 35 publications

References 17 publications

Accurately Achieving Target Busulfan Exposure in Children and Adolescents With Very Limited Sampling and the BestDose Software

Accurately Achieving Target Busulfan Exposure in Children and Adolescents With Very Limited Sampling and the BestDose Software

Quantification of Human Plasma-Busulfan Concentration by Liquid Chromatography-Tandem Mass Spectrometry

Comparison of LC-MS Assay and HPLC Assay of Busulfan in Clinical Pharmacokinetics Studies

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