PT  - JOURNAL ARTICLE
AU  - S R Biggs
AU  - L F Chasseaud
AU  - D R Hawkins
AU  - I Midgley
TI  - Determination of amitriptyline and its major basic metabolites in human urine by high-performance liquid chromatography.
DP  - 1979 Jul 01
TA  - Drug Metabolism and Disposition
PG  - 233--236
VI  - 7
IP  - 4
4099  - http://dmd.aspetjournals.org/content/7/4/233.short
4100  - http://dmd.aspetjournals.org/content/7/4/233.full
SO  - Drug Metab Dispos1979 Jul 01; 7
AB  - A high-performance liquid chromatographic method for the routine, simultaneous determination of amitriptyline and its basic metabolites in human urine has been developed. 10-Hydroxylated metabolites are analyzed as their 10,11-dehydro analogs, and primary and secondary amines as their N-trifluoroacetyl derivatives. The use of gradient elution enables amitryptyline, nortriptyline trifluoroacetate, desmethylnortriptyline trifluoroacetate, and the corresponding 10, 11-dehydro analogs to be separated from both each other and from the internal standard used. In this way all six compounds may be conveniently measured in a single chromatogram, with good sensitivity and accuracy. Following administration of a single oral dose (25 mg) of amitriptyline hydrochloride to two human subjects, no unchanged drug was found in any of the urine samples analyzed up to 72 hr after dosing, and only small amounts of nortriptyline and desmethylnortriptyline were observed. 10-hydroxynortriptyline was the major biotransformation product (about 40% of the dose) in urine, with 10-hydroxyamitriptyline and 10-hydroxydesmethylnortriptyline present as minor metabolites. During 72 hr after administration, approximately 60% of the dose was recovered as these five metabolites.