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A new generic column switching system for quantitation in cassette dosing using LC/MS/MS.
T Ohkawa1, Y Ishida, E Kanaoka
1Drug Metabolism and Pharmacokinetics, Developmental Research Laboratories, Shionogi and Co Ltd, 3-1-1, Futaba-cho, Toyonaka, Osaka 561-0825, Japan. tomoyuki.ohkawa@shionogi.co.jp
Journal of Pharmaceutical and Biomedical Analysis
|April 2, 2003
Summary
This study introduces a new column switching method for cassette dosing, enabling rapid pharmacokinetic screening of multiple drug candidates simultaneously. The validated system offers high accuracy and broad applicability for diverse compounds.
Area of Science:
- Pharmacokinetics
- Analytical Chemistry
- Drug Discovery
Background:
- Cassette dosing allows simultaneous pharmacokinetic assessment of multiple drug candidates in a single animal.
- Existing gradient methods for cassette dosing analysis face challenges with time-consuming mobile phase optimization and ionization suppression from common excipients like polyethyleneglycol.
- These limitations hinder the efficiency and applicability of high-throughput screening for new drug candidates.
Purpose of the Study:
- To develop a novel column switching method for cassette dosing analysis that overcomes the limitations of existing techniques.
- To enhance the sensitivity, applicability, and efficiency of pharmacokinetic screening for drug candidates.
- To provide a robust and user-friendly system for analyzing multiple compounds simultaneously.
Main Methods:
- A simple column switching system was designed using specified trap and analytical columns with a limited selection of mobile phases.
- Method optimization was streamlined, focusing solely on mobile phase selection, reducing optimization time to a few hours.
- The system was applied to analyze approximately 200 compounds administered in about 50 cassettes.
Main Results:
- The new column switching system demonstrated wide applicability and effectively avoided ionization suppression issues.
- Assay validation confirmed good accuracy and precision, with approximately 90% of compounds determined within 20% bias.
- The system proved highly efficient, requiring only a few hours for method optimization.
Conclusions:
- The developed column switching system is accurate and suitable for screening drug candidates using cassette dosing.
- The method offers broad applicability for a wide range of compounds, addressing previous limitations.
- This system represents a significant advancement for the efficient determination of cassette dosing samples in drug discovery.