@article{repository471,
         journal = {Scientia Pharmaceutica},
       publisher = {MDPI},
           title = {Quantification of 6-Mercaptopurine and Its
Metabolites in Patients with Acute Lympoblastic
Leukemia Using Dried Blood Spots and
UPLC-MS/MS},
             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(R) UPLC BEH AMIDA column of
1.7 {\ensuremath{\mu}}m (2.1 {$\times$} 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 {\ensuremath{>}} 119.09, 167.17 {\ensuremath{>}} 126.03, 380.16 {\ensuremath{>}} 168.00,
and 129.09 {\ensuremath{>}} 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 {$\times$} 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 {$\times$} 108

erythrocytes,
which includes concentrations below the hepatotoxic range. The method employed here can thus be
effectively utilized to support therapeutic drug monitoring.},
          author = {Supandi Supandi, Supandi}
}