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Tandem-in-time mass spectrometry as a quantitative bioanalytical tool
D T Rossi1, K L Hoffman, N Janiczek-Dolphin
1Department of Pharmacokinetics and Drug Metabolism, Parke-Davis Pharmaceutical Research, Division of Warner-Lambert Company, Ann Arbor, Michigan 48189, USA.
Analytical Chemistry
|January 7, 1998
Summary
Tandem-in-time mass spectrometry (MS/MS) offers selective and cost-effective quantification of therapeutic agents in plasma. This method achieved a 25 pg/mL limit of quantification for a novel drug, demonstrating high sensitivity and precision.
Area of Science:
- Analytical Chemistry
- Mass Spectrometry
- Biochemistry
Background:
- Tandem-in-time mass spectrometry (MS/MS) utilizes ion trapping and sequential fragmentation for selective analysis.
- Ion-trap detectors (ITD) offer advantages in ion throughput efficiency and cost compared to quadrupole or sector instruments.
- MS/MS techniques are crucial for precise quantification in complex biological matrices.
Purpose of the Study:
- To describe the application of capillary gas chromatography coupled with tandem-in-time mass spectrometry for quantifying a novel therapeutic agent in human plasma.
- To evaluate the sensitivity, precision, and dynamic range of the developed analytical method.
- To assess the overall instrumental performance and identify any limitations during routine use.
Main Methods:
- Capillary gas chromatography (GC) was coupled with tandem-in-time mass spectrometry (MS/MS) using an ion-trap detector (ITD).
- Precursor ions were generated, stored in a radio frequency (rf) trapping field, and sequentially fragmented.
- Electron ionization (EI) was employed to achieve M+ ions with minimal fragmentation for enhanced sensitivity.
Main Results:
- A quantification limit of 25 pg/mL (S/N ≈ 10, 15 fmol on-column) was achieved for the therapeutic agent in human plasma.
- Interday imprecision was less than or equal to 12.2% over a dynamic range extending to 10 ng/mL.
- Favorable ionization conditions led to high assay sensitivity, although some lack of ruggedness was noted in routine application.
Conclusions:
- Tandem-in-time mass spectrometry, when coupled with GC, provides a highly selective and sensitive method for quantifying therapeutic agents in plasma.
- The method demonstrates excellent sensitivity and precision, suitable for pharmacokinetic studies and therapeutic drug monitoring.
- While instrumental performance is adequate, further optimization may be needed to address ruggedness issues in routine clinical settings.