Quantification of 6-Mercaptopurine and Its Metabolites in Patients with Acute Lympoblastic Leukemia Using Dried Blood Spots and UPLC-MS/MS

Supandi Supandi, Supandi Quantification of 6-Mercaptopurine and Its Metabolites in Patients with Acute Lympoblastic Leukemia Using Dried Blood Spots and UPLC-MS/MS. Scientia Pharmaceutica.

[img]
Preview
Text
scipharm-86-00018.pdf

Download (979kB) | Preview
Official URL: http://www.mdpi.com/2218-0532/86/2/18

Abstract

This research aimed to quantitatively bioanalyze 6-mercaptopurine (6-MP), 6-methylmercaptopurine (6-MMP), and 6-thioguanosine-50 -monophosphate (6-TGMP) in dried blood spots (DBS) prepared from a small volume of acute lymphoblastic leukemia (ALL) patients. Analytes on the DBS card were extracted using 90% methanol with 5-fluorouracil (5-FU) as an internal standard. Analytical separation was performed on a Waters Acquity® UPLC BEH AMIDA column of 1.7 μm (2.1 × 100 mm) with a mobile phase mixture of 0.2% formic acid in water and 0.1% formic acid in acetonitrile-methanol, with gradient elution and a flow rate of 0.2 mL/min. Mass detection of 6-MP, 6-MMP, 6-TGMP, and 5-FU showed m/z values of 153.09 > 119.09, 167.17 > 126.03, 380.16 > 168.00, and 129.09 > 42.05, respectively. This DBS method had a run time of 5 min and yielded a linear calibration curve over a range of 25.5–1020 ng/mL for 6-MP, 6-MMP, and 6-TGMP. Analyte analysis in 22 of 24 ALL patients showed that the measured value of 6-TGMP as an active metabolite was in the range of 29–429 pmol/8 × 108 erythrocytes. Five of 22 patients had concentrations in a therapeutic range, which indicates that the treatment is effective, while 17 of 24 patients had concentrations below the therapeutic range, which indicates that a treatment dose adjustment is needed. The measured value of 6-MMP, an inactive metabolite, was in the range of 28–499 pmol/8 × 108 erythrocytes, which includes concentrations below the hepatotoxic range. The method employed here can thus be effectively utilized to support therapeutic drug monitoring.

Item Type: Article
Subjects: Q Science > Q Science (General)
Depositing User: admin repository uhamka
Date Deposited: 26 Apr 2018 08:10
Last Modified: 26 Apr 2018 08:10
URI: http://repository.uhamka.ac.id/id/eprint/471

Actions (login required)

View Item View Item