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Published on: November 15, 2017
Ternary-column system for high-throughput direct-injection bioanalysis by liquid chromatography/tandem mass
Y Q Xia1, D B Whigan, M L Powell
1Bioanalytical Research, Metabolism and Pharmacokinetics, Bristol-Myers Squibb Pharmaceutical Research Institute, P.O. Box 191, New Brunswick, NJ 08903-0191, USA.
Rapid Communications in Mass Spectrometry : RCM
|January 7, 2000
Summary
This study introduces a novel ternary-column online liquid chromatography-tandem mass spectrometry (LC/MS/MS) system for rapid drug quantification. The dual-column design significantly enhances sample throughput and system longevity in bioanalysis.
Area of Science:
- Analytical Chemistry
- Biochemistry
- Pharmacology
Background:
- High-throughput bioanalysis of drugs and metabolites is crucial for drug development.
- Existing online liquid chromatography-tandem mass spectrometry (LC/MS/MS) methods require optimization for speed and efficiency.
- Parallel processing in bioanalytical workflows can improve sample throughput.
Purpose of the Study:
- To develop and validate an improved online LC/MS/MS system for high-throughput drug quantitation.
- To enhance sample throughput and system robustness using a ternary-column configuration with dual extraction columns.
- To establish a rapid bioanalytical method for a guanidine-containing drug candidate in rat plasma.
Main Methods:
- Development of a ternary-column online LC/MS/MS system featuring dual parallel extraction columns and one analytical column.
- Utilized a ten-port switching valve for seamless sample processing and column equilibration.
- Employed direct injection of plasma samples, selected reaction monitoring (SRM) for detection, and positive ion electrospray ionization.
Main Results:
- Achieved a significantly reduced injection cycle time due to parallel column equilibration.
- Demonstrated high sample throughput with a total run time of only 1.6 minutes per sample.
- Validated a quantitative method for a guanidine-containing drug in rat plasma with excellent precision and accuracy (within 6.6%) over a 1.00-200 ng/mL range.
Conclusions:
- The developed ternary-column online LC/MS/MS system offers a substantial improvement in sample throughput for bioanalytical applications.
- The parallel dual extraction column design enhances system efficiency and extends the usable life of extraction columns.
- This optimized approach provides a robust and rapid method for quantitative drug analysis in biological matrices, accelerating drug development timelines.
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