Bioanalytical method for quantitative determination of mithramycin analogues in mouse plasma by HPLC-QTOF.

08:00 EDT 30th March 2019 | BioPortfolio

Summary of "Bioanalytical method for quantitative determination of mithramycin analogues in mouse plasma by HPLC-QTOF."

Mithramycin (MTM) has potent anticancer activity, but severe toxicities restrict its clinical use. Semi-synthetic approaches have yielded novel MTM analogues with potentially lower toxicity and similar efficacy. In an effort to transition these analogs into in vivo models, a bioanalytical method was developed for their quantification in mouse plasma. Here we present the validation of the method for the quantitation of mithramycin SA-tryptophan (MTMSA-Trp) as well as the applicability of the methodology for assaying additional analogues, including MTM, mithramycin SK (MTMSK), and mithramycin SA-phenylalanine (MTMSA-Phe) with run times of six minutes. Assay linearity ranged from 5 to 100ng/mL. Accuracy of calibration standards and quality control samples were within 15% of nominal with precision variability of less than 20%. MTMSA-Trp was stable for 30 days at -80°C and for at least three freeze-thaw cycles. Methanol (-80°C) extraction afforded 92% of MTMSA-Trp from plasma. Calibration curves for MTM and analogues were also linear from ≤5 to 100ng/mL. This versatile method was used to quantitate MTM analogues in plasma samples collected during preclinical pharmacokinetic studies.


Journal Details

This article was published in the following journal.

Name: Biomedical chromatography : BMC
ISSN: 1099-0801
Pages: e4544


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