Simultaneous determination of fludarabine and clofarabine in human plasma by LC–MS/MS

Huang, Liusheng; Lizak, Patricia; Dvorak, Christopher C.; Aweeka, Francesca; Long-Boyle, Janel

doi:10.1016/j.jchromb.2014.04.045

Cited by 14 publications

(16 citation statements)

References 15 publications

(16 reference statements)

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“…Plasma and PBMC samples were analyzed for f-ara-a and f-ara-ATP using 2 different validated liquid chromatography-tandem mass spectrometry methods, as previously described [28,29]. The fara-a assay was linear in the range of 2 ng/mL to 800 ng/mL.…”

Section: Methodsmentioning

confidence: 99%

Pharmacokinetics and Model-Based Dosing to Optimize Fludarabine Therapy in Pediatric Hematopoietic Cell Transplant Recipients

Ivaturi

Dvorak

Chan

et al. 2017

Biology of Blood and Marrow Transplantation

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A prospective multicenter study was conducted to characterize the pharmacokinetics (PK) and pharmacodynamics (PD) of fludarabine plasma (f-ara-a) and intracellular triphosphate (f-ara-ATP) in children undergoing hematopoietic cell transplantation (HCT) and receiving fludarabine with conditioning. Plasma and peripheral blood mononuclear cells (PBMCs) were collected over the course of therapy for quantitation of f-ara-a and f-ara-ATP. Nonlinear mixed-effects modeling was used to develop the PK model, including identification of covariates impacting drug disposition. Data from a total of 133 children (median age, 5 years; range, .2 to 17.9) undergoing HCT for a variety of malignant and nonmalignant disorders were available for PK-PD modeling. The implementation of allometric scaling of PK parameters alone was insufficient to describe drug clearance, particularly in very young children. Renal impairment was predicted to increase drug exposure across all ages. The rate of f-ara-a entry into PBMCs (expressed in pmoles per million cells) decreased over the course of therapy, resulting in 78% lower f-ara-ATP after the fourth dose (1.7 pmoles/million cells [range, .2 to 7.2]) compared with first dose (7.9 pmoles/million cells [range, .7 to 18.2]). The overall incidence of treatment-related mortality (TRM) was low at 3% and 8% at days 60 and 360, respectively, and no association with f-ara-a exposure and TRM was found. In the setting of malignancy, disease-free survival was highest at 1 year after HCT in subjects achieving a systemic f-ara-a cumulative area under the curve (cAUC) greater than 15 mg*hour/L compared to patients with a cAUC less than 15 mg*hour/L (82.6% versus 52.8% P = .04). These results suggest that individualized model-based dosing of fludarabine in infants and young children may reduce morbidity and mortality through improved rates of disease-free survival and limiting drug-related toxicity. ClinicalTrials.gov Identifier: NCT01316549

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Section: Methodsmentioning

confidence: 99%

Pharmacokinetics and Model-Based Dosing to Optimize Fludarabine Therapy in Pediatric Hematopoietic Cell Transplant Recipients

Ivaturi

Dvorak

Chan

et al. 2017

Biology of Blood and Marrow Transplantation

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“…The method was validated in terms of precision, accuracy, matrix effect, and stability, following the procedures as described previously [ 10 ]. One set of calibrators was processed for each run and injected in the beginning of the batch run.…”

Section: Methodsmentioning

confidence: 99%

“…LC-MS/MS assays have also been reported, but the sensitivity of these assays requires concentrations ≥100 ng/mL [ 7 – 9 ]. Trichloroacetic acid (TCA) has been used in sample preparation to remove proteins, especially for hydrophilic analytes, with the advantage of direct injection of resulting sample solution [ 10 ]. We found that TCA not only increased the retention time but also the MS signal of TBM.…”

Section: Introductionmentioning

confidence: 99%

Determination of Tobramycin in M₉ Medium by LC-MS/MS: Signal Enhancement by Trichloroacetic Acid

Huang

Haagensen

Verotta

et al. 2018

Journal of Analytical Methods in Chemistry

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It is well known that ion-pairing reagents cause ion suppression in LC-MS/MS methods. Here, we report that trichloroacetic acid increases the MS signal of tobramycin. To support studies of an in vitro pharmacokinetic/pharmacodynamic simulator for bacterial biofilms, an LC-MS/MS method for determination of tobramycin in M9 media was developed. Aliquots of 25 μL M9 media samples were mixed with the internal standard (IS) tobramycin-d5 (5 µg/mL, 25 µL) and 200 µL 2.5% trichloroacetic acid. The mixture (5 µL) was directly injected onto a PFP column (2.0 × 50 mm, 3 µm) eluted with water containing 20 mM ammonium formate and 0.14% trifluoroacetic acid and acetonitrile containing 0.1% trifluoroacetic acid in a gradient mode. ESI+ and MRM with ion m/z 468 → 324 for tobramycin and m/z 473 → 327 for the IS were used for quantification. The calibration curve concentration range was 50–25000 ng/mL. Matrix effect from M9 media was not significant when compared with injection solvents, but signal enhancement by trichloroacetic acid was significant (∼3 fold). The method is simple, fast, and reliable. Using the method, the in vitro PK/PD model was tested with one bolus dose of tobramycin.

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“…The separation was achieved on a reversed‐phase C18 column with 0.1% formic acid:methanol (30:70, v /v) in an isocratic mode at 1 mL/min flow rate. Huang, Lizak, Dvorak, Aweeka, and Long‐Boyle () reported a method for a simultaneous quantification of fludarabine and clofarabine with 2‐chloro adenosine as an internal standard in human plasma on LC–MS/MS by adopting a trichloro acetic acid for precipitation. The column used was Eclipse extend C18, and the mobile phase comprised 1 mM ammonium hydroxide (pH 9.6) and acetonitrile in a gradient mode (Huang et al, ).…”

Section: Case Studiesmentioning

confidence: 99%

A review of bioanalytical methods for chronic lymphocytic leukemia drugs and metabolites in biological matrices

Suresh

Trivedi

Srinivas³

et al. 2019

Biomedical Chromatography

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Quantitation of drugs used for the treatment of chronic lymphocytic leukemia in various biological matrices during both pre‐clinical and clinical developments is very important, often in routine therapeutic drug monitoring. The first developed methods for quantitation were traditionally done on LC in combination with either UV or fluorescence detection. However, the emergence of LC with mass spectrometry in tandem in early 1990s has revolutionized the quantitation as it has provided better sensitivity and selectivity within a shorter run time; therefore it has become the choice of method for the analysis of various drugs. In this article, an overview of various bioanalytical methods (HPLC or LC–MS/MS) for the quantification of drugs for the treatment of chronic lymphocytic leukemia, along with applicability of these methods, is given.

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Simultaneous determination of fludarabine and clofarabine in human plasma by LC–MS/MS

Cited by 14 publications

References 15 publications

Pharmacokinetics and Model-Based Dosing to Optimize Fludarabine Therapy in Pediatric Hematopoietic Cell Transplant Recipients

Pharmacokinetics and Model-Based Dosing to Optimize Fludarabine Therapy in Pediatric Hematopoietic Cell Transplant Recipients

Determination of Tobramycin in M₉ Medium by LC-MS/MS: Signal Enhancement by Trichloroacetic Acid

A review of bioanalytical methods for chronic lymphocytic leukemia drugs and metabolites in biological matrices

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Simultaneous determination of fludarabine and clofarabine in human plasma by LC–MS/MS

Cited by 14 publications

References 15 publications

Pharmacokinetics and Model-Based Dosing to Optimize Fludarabine Therapy in Pediatric Hematopoietic Cell Transplant Recipients

Pharmacokinetics and Model-Based Dosing to Optimize Fludarabine Therapy in Pediatric Hematopoietic Cell Transplant Recipients

Determination of Tobramycin in M9 Medium by LC-MS/MS: Signal Enhancement by Trichloroacetic Acid

A review of bioanalytical methods for chronic lymphocytic leukemia drugs and metabolites in biological matrices

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Determination of Tobramycin in M₉ Medium by LC-MS/MS: Signal Enhancement by Trichloroacetic Acid