Determination of amitriptyline and its main metabolites in human plasma samples using HPLC-DAD: application to the determination of metabolic ratios after single oral dose of amitriptyline

Journal of the Brazilian Chemical Society

Tzvetkov, Mladen¹  Linden, Rafael¹  Souto, André Arigony¹  Universität Göettingen, Göettingen, Germany¹  Ziulkoski, Ana Luiza¹  Pontifícia Universidade Católica do Rio Grande do Sul, Porto Alegre, Brazil¹  Wingert, Maína¹  Antunes, Marina Venzon¹  Centro Universitário Feevale, Novo Hamburgo, Brazil¹  Tonello, Paula¹ 

关键词: amitriptyline;    HPLC-DAD;    CYP2C19;    metabolic ratios;   

DOI  :  10.1590/S0103-50532008000100007

学科分类：化学（综合）

来源: SciELO

【 摘 要 】

A simple and sensitive HPLC-DAD method for the simultaneous determination of amitriptyline, nortriptyline, E-10-hydroxyamitriptyline, Z-10-hydroxyamitriptyline, E-10-hydroxynortriptyline, Z-10-hydroxynortriptyline and desmethylnortriptyline in human plasma samples was developed and validated. The method employs a two step liquid-liquid extraction and a reversed phase separation with isocratic elution. Precision assays showed R.S.D % lower than 12.1% and accuracy was in the range of 93.1 to 102.5%. Lowest Limit of detection was 5 ng mL-1 for all analytes. Metabolic ratios of amitriptyline demethylation were evaluated in individuals genotyped for CYP2C19, with clear differences between volunteers with zero or two active alleles. The method is suitable for therapeutic drug monitoring of patients under amitriptyline treatment, also allowing the indication of CYP2C19 activity.

【 授权许可】

Unknown