Clinical Applications of LC-MS Drug Testing: Therapeutic Drug Monitoring and Pharmacokinetics
Liquid chromatography-mass spectrometry (LC-MS) is an analytical chemistry technique that combines liquid chromatography and mass spectrometry. The liquid chromatography component separates individual elements of a mixture based on the affinity with the stationary phase, while the MS unit detects separated components based on their mass-to-charge ratio.
Mass spectrometry is the primary choice of detection technique for LC-MS drug testing. It is a powerful tool for analyzing complex mixtures and their components. LC-MS services increasingly employ this tool for sensitive, accurate, and reproducible data. LC-MS testing is applied at different stages of drug discovery and development. Scientists use them in metabolism studies, in vitro assay development, identification of degradation and impurities, pharmacokinetic assay, and therapeutic drug monitoring.
The current article discusses the LC-MS and LC-MS/MS applications in therapeutic drug monitoring and pharmacokinetic evaluation. However, robust LC-MS method development and validation is vital for generating reliable, accurate, and reproducible results.
LC-MS drug testing for pharmacokinetic evaluations
Before developing a drug product, the compound is studied to identify its therapeutic value. Pharmacokinetics studies the effect of drug absorption, distribution, metabolism, and excretion by the body. Bioavailability is another crucial criterion for demonstrating drug efficacy. Bioavailability refers to the quantity of drug available at the site of action.
Once a drug molecule is metabolized, an active metabolite is released from the compound. This metabolite can be pharmacokinetically active, and thorough characterization of all metabolites is necessary to identify drugs with improved stability, pharmacological activity, and metabolic stability. Besides, this testing ensures drug safety as it demonstrates an improved toxicology profile of the drug.
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LC-MS testing for therapeutic drug monitoring
Therapeutic drug monitoring is crucial to optimize and determine critical doses with a narrow therapeutic range. Drug monitoring can help design drug dosages with desired effectiveness and reduced side effects. Scientists have been performing therapeutic drug monitoring using immunoassays. However, immunoassays suffer from non-specific interference, and hence, therapeutic drug monitoring requires robust bioanalytical tools such as LC-MS assays for desired accuracy and reliability.
LC-MS assays have been employed extensively in bioanalytical laboratories for more than a decade. They are increasingly becoming crucial for analyzing concentrations of prescribed drugs. Due to increased specificity and sensitivity compared to other analytical methods, LC-MS assays are becoming a primary choice of tool for therapeutic drug monitoring. Besides, LC-MS assays may be the only suitable tool for quantifying drugs without natural fluorophores or chromophores. However, selecting the right column technology, sample preparation method, mass spectrometric conditions, and internal standard is critical for ensuring accurate measurements and avoiding interference from drug metabolites and matrix effects. LC-MS assays are more involved than automated immunoassays during analysis. However, technological advancements such as online solid phase extraction and the development of sampling robots have made LC-MS assays suitable for therapeutic drug monitoring.
Conclusion
LC-MS assays are robust tools for several clinical applications, including pharmacokinetic evaluations and therapeutic drug monitoring. Scientists should explore novel avenues, such as automation, for accelerating LC-MS applications beyond routine drug testing and biomedical experiments. However, LC-MS method development and validation will remain critical for reliable bioanalysis.
