Biggs S R, Chasseaud L F, Hawkins D R, Midgley I
Drug Metab Dispos. 1979 Jul-Aug;7(4):233-6.
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.
已开发出一种高效液相色谱法，用于常规同时测定人尿中阿米替林及其主要代谢物。10-羟基化代谢物作为其10,11-脱氢类似物进行分析，伯胺和仲胺作为其N-三氟乙酰基衍生物进行分析。梯度洗脱的使用使得阿米替林、去甲替林三氟乙酸盐、去甲替林三氟乙酸盐以及相应的10,11-脱氢类似物能够相互分离，并与所使用的内标物分离。通过这种方式，所有六种化合物都可以在一张色谱图中方便地测定，具有良好的灵敏度和准确性。在两名人体受试者单次口服25mg盐酸阿米替林后，在给药后长达72小时的任何尿液样本中均未发现未变化的药物，仅观察到少量的去甲替林和去甲替林。10-羟基去甲替林是尿液中的主要生物转化产物（约占剂量的40%），10-羟基阿米替林和10-羟基去甲替林作为次要代谢物存在。在给药后的72小时内，约60%的剂量以这五种代谢物的形式回收。
