Determination of l-α-acetylmethadol, l-α-noracetylmethadol and l-α-dinoracetylmethadol in plasma by gas chromatography—mass spectrometry

A method is described for the simultaneous determination of l-α-acetylmethadol (LAAM) and its N-demethylated metabolites, l-α-noracetylmethadol (norLAAM) and l-α-dinoracetylmethadol (dinorLAAM), in plasma by gas chromatography—chemical ionization mass spectrometry. Deuterated internal standards for...

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Bibliographic Details
Published in:Journal of chromatography. B, Biomedical applications Biomedical applications, 1994-05, Vol.655 (2), p.201-211
Main Authors: Thomas, Brian F., Jeffcoat, A.Robert, Myers, Mary W., Mathews, James M., Cook, C.Edgar
Format: Article
Language:English
Subjects:
Analysis
Animals
Biological and medical sciences
Deuterium
Female
Gas Chromatography-Mass Spectrometry - methods
Gas Chromatography-Mass Spectrometry - standards
Gas Chromatography-Mass Spectrometry - statistics & numerical data
General pharmacology
Humans
Male
Medical sciences
Methadyl Acetate - analogs & derivatives
Methadyl Acetate - blood
Pharmacology. Drug treatments
Quality Control
Rats
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Summary:A method is described for the simultaneous determination of l-α-acetylmethadol (LAAM) and its N-demethylated metabolites, l-α-noracetylmethadol (norLAAM) and l-α-dinoracetylmethadol (dinorLAAM), in plasma by gas chromatography—chemical ionization mass spectrometry. Deuterated internal standards for each analyte serve as carriers and control for recovery during sample purification on a solid-phase extraction column (C 18), and subsequent separation and analysis on a DB-17 capillary column. With this method, we have determined levels of LAAM, norLAAM, and dinorLAAM in small volumes of plasma (100 μl). The limit of quantitation for all analytes was approximately 1.0 ng/g plasma and the limit of detection was approximately 0.5 ng/g plasma. An experimental application is also described where these analytes are quantitated in plasma obtained from rats before, during, and after chronic administration of LAAM-HCl. Since this technique affords a selective and sensitive means of detection of LAAM and its active, N-demethylated metabolites in small samples of blood, it may enable patient compliance to be more easily assessed by allowing samples to be collected by a simple finger-prick technique.
ISSN:0378-4347
1572-6495
DOI:10.1016/0378-4347(94)00097-2