Development of a methodology to make individual estimates of the precision of liquid chromatography-tandem mass spectrometry drug assay results for use in population pharmacokinetic modeling and the optimization of dosage regimens

PloS One
Gellért Balázs KarvalyRoger W Jelliffe

Abstract

The clinical value of therapeutic drug monitoring can be increased most significantly by integrating assay results into clinical pharmacokinetic models for optimal dosing. The correct weighting in the modeling process is 1/variance, therefore, knowledge of the standard deviations (SD) of each measured concentration is important. Because bioanalytical methods are heteroscedastic, the concentration-SD relationship must be modeled using assay error equations (AEE). We describe a methodology of establishing AEE's for liquid chromatography-tandem mass spectrometry (LC-MS/MS) drug assays using carbamazepine, fluconazole, lamotrigine and levetiracetam as model analytes. Following method validation, three independent experiments were conducted to develop AEE's using various least squares linear or nonlinear, and median-based linear regression techniques. SD's were determined from zero concentration to the high end of the assayed range. In each experiment, precision profiles of 6 ("small" sample sets) or 20 ("large" sample sets) out of 24 independent, spiked specimens were evaluated. Combinatorial calculations were performed to attain the most suitable regression approach. The final AEE's were developed by combining the SD's of the assa...Continue Reading

References

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Citations

Jan 16, 2021·Clinical Pharmacokinetics·Mehdi El HassaniAmélie Marsot
Sep 4, 2021·Pharmacology Research & Perspectives·Gellért Balázs KarvalyAndrás Zsáry
May 1, 2021·Therapeutic Drug Monitoring·Octavia M Peck Palmer, Amitava Dasgupta

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BETA
pharmacotherapy
pharmacotherapists

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