Your browser doesn't support javascript.
loading
Determination of 6-thioguanine and 6-methylmercaptopurine in dried blood spots using liquid chromatography-tandem mass spectrometry: Method development, validation and clinical application.
Lampic, Kristina; Trontelj, Jurij; Prosen, Helena; Drobne, David; Smid, Alenka; Vovk, Tomaz.
Afiliação
  • Lampic K; Lek Pharmaceuticals d.d., Ljubljana, Slovenia; University of Ljubljana, Faculty of Pharmacy, Ljubljana, Slovenia; University of Ljubljana, Faculty of Chemistry and Chemical Technology, Ljubljana, Slovenia.
  • Trontelj J; University of Ljubljana, Faculty of Pharmacy, Ljubljana, Slovenia.
  • Prosen H; University of Ljubljana, Faculty of Chemistry and Chemical Technology, Ljubljana, Slovenia.
  • Drobne D; University Medical Centre Ljubljana, Department of Gastroenterology, Ljubljana, Slovenia.
  • Smid A; University of Ljubljana, Faculty of Pharmacy, Ljubljana, Slovenia.
  • Vovk T; University of Ljubljana, Faculty of Pharmacy, Ljubljana, Slovenia. Electronic address: tomaz.vovk@ffa.uni-lj.si.
Clin Chim Acta ; 499: 24-33, 2019 Dec.
Article em En | MEDLINE | ID: mdl-31449774
BACKGROUND: Therapeutic drug monitoring of azathioprine metabolites is required for pharmacotherapy individualisation in patients with inflammatory bowel disease. Currently mainly hemolysates are used, requiring long sample preparation and showing limited analytes stability. Therefore, a quantitative LC-MS/MS method for determination of 6-thioguanine (6-TG) and 6-methylmercaptopurine (6-MMP) in dried blood spot samples (DBS) was developed. METHODS: Analysis involves liquid extraction from 30 µL blood spot, hydrolysis and quantification with LC-MS/MS. RESULTS: Method met the validation criteria in terms of selectivity, linearity, accuracy, and precision in a range from 50 to 5300 pmol/8 × 108 Ery for 6-TG and from 260 to 5300 pmol/8 × 108 Ery for 6-MMP. Range can be increased to 8000 pmol/8 × 108 Ery. No matrix effect was observed and the recovery was >80%. DBS specific validation parameters were confirmed: spot homogeneity, no influence of blood spot volume (>30 µL) on 6 mm DBS disk, and absence of haematocrit effect. DBS samples were stable for at least one month at temperatures from -20 to 40 °C. Clinical validation confirmed that DBS method and routine clinical method with hemolysate samples give comparable results and enable similar clinical decisions. CONCLUSIONS: The newly developed DBS method is simple and presents an alternative to conventional methods for therapeutic drug monitoring of azathioprine metabolites.
Assuntos
Palavras-chave

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Tioguanina / Teste em Amostras de Sangue Seco / Mercaptopurina Tipo de estudo: Prognostic_studies Limite: Humans Idioma: En Revista: Clin Chim Acta Ano de publicação: 2019 Tipo de documento: Article País de afiliação: Eslovênia

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Tioguanina / Teste em Amostras de Sangue Seco / Mercaptopurina Tipo de estudo: Prognostic_studies Limite: Humans Idioma: En Revista: Clin Chim Acta Ano de publicação: 2019 Tipo de documento: Article País de afiliação: Eslovênia