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Determination of paracetamol in mouse, rat and dog plasma samples by laser diode thermal desorption--APCI-MS/MS
John G Swales1, David G Temesi, Mark Denn
1Global DMPK Innovative Medicines, In Vivo Screening & Profiling, Astrazeneca R&D, Alderley Park, Macclesfield, Cheshire, UK. john.swales@astrazeneca.com
Background:
Laser diode thermal desorption (LDTD) is a relatively new sample introduction interface for MS. Analysis times are short as the technique does not require time-consuming separation steps, such as conventional HPLC, thus saving on the use of organic solvents, modifiers and cost, relating to their subsequent disposal. This paper compares the merits of LDTD-APCI-MS/MS and LC-MS/MS for the analysis of paracetamol (acetaminophen) in plasma from different species.
Results:
LDTD-APCI-MS/MS compared favorably with our existing high-throughput generic LC-MS/MS method giving improved data quality. LDTD-APCI-MS/MS assay performance in terms of accuracy and precision in mouse, rat and dog plasma were within our local acceptance criteria (±30%). Run times were reduced approximately tenfold, while saving approximately 200 ml of solvent per 96-well plate.
Conclusion:
A rapid, sensitive and robust assay is reported. The method was successfully used for the analysis of spiked mouse, rat and dog plasma samples and the determination of oral pharmacokinetics. Reductions in electrical power and reagent consumption position LDTD as an environmentally 'green' bioanalytical method.
