Assay of ezlopitant, a substance P receptor antagonist, and metabolites in biological matrices by gas chromatography with mass spectrometric detection: simultaneous analysis of a benzyl alcohol and alkene

A method for the analysis of the substance P antagonist ezlopitant and two active metabolites in serum using solid-phase extraction followed by GC–MS analysis is described. The linear dynamic range was 1.0 to 100 ng/ml and precision and accuracy over this range were within 15%. Upon injection of rec...

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Bibliographic Details
Published in:Journal of chromatography. B, Biomedical sciences and applications Biomedical sciences and applications, 2000-07, Vol.744 (2), p.333-343
Main Authors: Reed-Hagen, Anne E., Janiszewski, John S., Cole, Roderic O., Obach, R.Scott
Format: Article
Language:English
Subjects:
Alkenes - analysis
Alkenes - blood
Benzyl Alcohol - analysis
Benzyl Alcohol - blood
Benzylamines - analysis
Benzylamines - blood
Benzylamines - pharmacology
Biological and medical sciences
Bridged Bicyclo Compounds, Heterocyclic - analysis
Bridged Bicyclo Compounds, Heterocyclic - blood
Bridged Bicyclo Compounds, Heterocyclic - pharmacology
Ezlopitant
Gas Chromatography-Mass Spectrometry - methods
Medical sciences
Neurokinin-1 Receptor Antagonists
Neuropharmacology
Neurotransmitters. Neurotransmission. Receptors
Peptidergic system (neuropeptide, opioid peptide, opiates...). Adenosinergic and purinergic systems
Pharmacology. Drug treatments
Substance P
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Summary:A method for the analysis of the substance P antagonist ezlopitant and two active metabolites in serum using solid-phase extraction followed by GC–MS analysis is described. The linear dynamic range was 1.0 to 100 ng/ml and precision and accuracy over this range were within 15%. Upon injection of reconstituted sample extracts into the hot injector port of the gas chromatograph, the benzyl alcohol metabolite undergoes a small amount of spontaneous dehydration to the alkene metabolite. We have incorporated an additional hexadeuterated internal standard of the benzyl alcohol into the assay to permit measurement of the extent of dehydration in each sample. This novel approach should be generally applicable to the simultaneous determination of benzyl alcohols and corresponding alkenes by GC–MS when the possibility exists that the alcohol can undergo spontaneous dehydration to the alkene in the injector port of GC instrumentation.
ISSN:0378-4347
1387-2273
DOI:10.1016/S0378-4347(00)00252-8