Selected ion monitoring assay for the antidepressant maprotiline

A procedure is described which permits the determination of maprotiline in biological fluids at concentrations ranging from 0.5 to 150 ng ml-1. It relies on the use of N-desmethylclomipramine or isotope labeled maprotiline as the internal standard, on derivatization of the secondary amines with heptafluorobutyric anhydride, and on the combined use of gas chromatography with chemical ionization mass spectrometry and computerized data handling. The assaying procedure is specific, accurate and precise. It is suitable for routine analyses and has sufficient sensitivity to permit monitoring the human blood levels expected from a single therapeutic dose for a week or longer. The method, which can monitor simultaneously isotope labeled and unlabeled maprotiline, can be used to great advantage for reducing variability problems encountered in bioavailability studies.