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A High-Throughput LC-MS/MS Method for the Simultaneous Quantification of Twenty-Seven Drug Molecules in Ocular
Brock Matter1, David W A Bourne1, Uday B Kompella2
1Pharmaceutical Sciences, University of Colorado Anschutz Medical Campus, 12850 East Montview Blvd., C238-V20, Aurora, Colorado, 80045, USA.
AAPS Pharmscitech
|July 12, 2022
Summary
A new liquid chromatography-tandem mass spectrometry (LC-MS/MS) method enables simultaneous analysis of 27 drugs with diverse properties. This validated assay accurately quantifies drug partition coefficients and recovery in eye tissues.
Area of Science:
- Analytical Chemistry
- Pharmacokinetics
- Ocular Drug Delivery
Background:
- Simultaneous analysis of diverse drug compounds presents analytical challenges.
- Accurate determination of drug partition coefficients and tissue distribution is crucial for drug development.
Purpose of the Study:
- To develop and validate a rapid, sensitive LC-MS/MS method for simultaneous quantification of a 27-drug cassette.
- To apply the method for assessing drug partition coefficients and ocular tissue recovery.
Main Methods:
- Development of an LC-MS/MS assay using a QTrap 4500 system with gradient elution.
- Validation of the method for drugs with a wide range of lipophilicity, including LLOQ and reproducibility.
- Application of the method to measure partition coefficients and quantify drug recovery from rabbit aqueous humor and cornea.
Main Results:
- A validated 18-minute LC-MS/MS method was established for simultaneous analysis of 27 drugs.
- Lower limits of quantification (LLOQ) ranged from 0.5 to 40 fmols on column with %RSD < 20%.
- Measured partition coefficients correlated with predicted values (r²=0.5-0.7), and drug recovery from eye tissues was high (≥79% in aqueous humor, 61-67% in cornea).
Conclusions:
- A rapid, sensitive, and validated LC-MS/MS method was successfully developed for simultaneous drug quantification.
- The method is suitable for N-in-one drug delivery screening and assessing drug properties in biological matrices.
- This assay facilitates efficient analysis of drug cassettes in aqueous solutions and ocular tissues.
