AI Article Synopsis

  • A multiplex LC-MS/MS assay has been developed to simultaneously measure mycophenolic acid (MPA) and several triazole antifungal drugs in serum, which is crucial for monitoring treatment in immunocompromised patients.
  • The method involves a five-minute chromatographic separation and has shown excellent precision and a wide dynamic range for all measured drugs, with low limits of detection and quantitation.
  • Validation results indicate that the assay performs well on different HPLC systems, demonstrating reliability and consistency for clinical applications.

Article Abstract

Background: As an active metabolite of a commonly prescribed immunosuppressant, mycophenolic acid (MPA) levels are often monitored to prevent organ rejection following a transplant. Triazoles are often prescribed for treatment of invasive fungal infections in immunocompromised patients. Due to the variability in individual pharmacokinetics and drug-drug interactions, therapeutic drug monitoring is recommended for triazole antifungals. A multiplex LC-MS/MS assay has been developed that can quantify both MPA and triazole drugs in serum.

Methods: A sample preparation procedure was established to spike in internal standard compounds and precipitate proteins. Reversed-phase chromatographic separation was performed on a C18 column with an analysis time of five minutes per sample. The mass spectrometer was operated in multiple reaction monitoring mode. The method was validated on two HPLC systems interfaced with either a Triple Quad 6500 or an API 4000 instrument.

Results: The multiplex assay was linear over a wide dynamic range with analyte measurable ranges of 0.4-48 μg/mL for MPA, 0.1-12 μg/mL for posaconazole, and 0.2-24 μg/mL for voriconazole, itraconazole, hydroxyitraconazole, and isavuconazole. The between-day and intraday imprecisions were less than 10 %. Limits of detection were below 0.04 ug/mL with limits of quantitation below 0.2 μg/mL. Method comparison studies against the current in-house method met acceptance criteria. The instrument comparison study demonstrated a strong correlation between data collected from the two systems.

Conclusion: A robust multiplex LC-MS/MS assay was developed and validated for monitoring MPA and triazoles drug levels in a clinical laboratory. The assay performance on two distinct instruments was acceptable and comparable.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC11225655PMC
http://dx.doi.org/10.1016/j.jmsacl.2024.06.001DOI Listing

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