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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.
This article was published in the following journal.
Name: Biomedical chromatography : BMC
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To establish a high performance liquid chromatography (HPLC) method for the determination of 8-methoxypsoralen (8-MOP) in mouse plasma and apply it to a pharmacokinetic study of 8-MOP.
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Quantitative determination of receptor (binding) proteins in body fluids or tissue using radioactively labeled binding reagents (e.g., antibodies, intracellular receptors, plasma binders).
Locations, on the GENOME, of GENES or other genetic elements that encode or control the expression of a quantitative trait (QUANTITATIVE TRAIT, HERITABLE).
The branch of chemistry dealing with detection (qualitative) and determination (quantitative) of substances. (Grant & Hackh's Chemical Dictionary, 5th ed)
A method of measuring the effects of a biologically active substance using an intermediate in vivo or in vitro tissue or cell model under controlled conditions. It includes virulence studies in animal fetuses in utero, mouse convulsion bioassay of insulin, quantitation of tumor-initiator systems in mouse skin, calculation of potentiating effects of a hormonal factor in an isolated strip of contracting stomach muscle, etc.
A method of tissue ablation and bleeding control that uses argon plasma (ionized argon gas) to deliver a current of thermocoagulating energy to the area of tissue to be coagulated.
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An assay is an analytic procedure for qualitatively assessing or quantitatively measuring the presence or amount or the functional activity of a target entity. This can be a drug or biochemical substance or a cell in an organism or organic sample. ...