Determination of 6-thioguanine and 6-methylmercaptopurine in dried blood spots using liquid chromatography-tandem mass spectrometry : method development, validation and clinical application
Lampič, Kristina, farmacevtka ...
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 30microL 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 5300pmol/8108 Ery for 6-TG and from 260 to 5300pmol/8 108 Ery for 6-MMP. Range can be increased to 8000pmol/8108 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 (>30microL) on 6mm 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.
Determination of 6-thioguanine and 6-methylmercaptopurine in dried blood spots using liquid chromatography-tandem mass spectrometry : method development, validation and clinical application
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2019-12-29
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4780913
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Farmacevtska tehnologija: od dostavnih sistemov učinkovin do terapijskih izidov zdravil pri otrocih in starostnikih
P1-0189-2018
Javna agencija za znanstvenoraziskovalno in inovacijsko dejavnost Republike Slovenije
Raziskave in razvoj analiznih metod in postopkov
P1-0153-2015
Javna agencija za znanstvenoraziskovalno in inovacijsko dejavnost Republike Slovenije
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