ANALYSIS OF 6-MERCAPTOPURINE AND 6-METHYLMERCAPTOPURINE IN DRIED BLOOD SPOTS USING LIQUID CHROMATOGRAPHY-TANDEM MASS SPECTROMETRY AND ITS APPLICATION IN CHILDHOOD ACUTE LYMPHOBLASTIC LEUKEMIA PATIENTS

Supandi, SupandidanYahdiana Harahap, YahdianadanHarmita, HarmitadanRizka Andalusia, RizkadanMarlina Ika, Marlina (2017) ANALYSIS OF 6-MERCAPTOPURINE AND 6-METHYLMERCAPTOPURINE IN DRIED BLOOD SPOTS USING LIQUID CHROMATOGRAPHY-TANDEM MASS SPECTROMETRY AND ITS APPLICATION IN CHILDHOOD ACUTE LYMPHOBLASTIC LEUKEMIA PATIENTS. Asian Journal of Pharmaceutical and Clinical Research, 10 (9). pp. 120-125. ISSN 0974-2441

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Official URL: http://dx.doi.org/10.22159/ajpcr.2017.v10i9.19790

Abstract

Objective: To analyze and validate 6-mercaptopurine (6-MP) and 6-methylmercaptopurine (6-MMP) in dried blood spots (DBS) using liquid chromatography-tandem mass spectrometry (LC/MS-MS). Methods: Bio-sampling dried blood spot with DBS-CAMAG® paper diameter of 8 mm and extracted with acetonitrile-methanol (1:3) containing internal standard 5-fluorouracil (5-FU). Separation was performed with C18 column Acquity® 1.7 μm (2.1 mm × 100 mm), with a mobile phase mixture of 0.1% formic acid in water 0.1% formic acid in acetonitrile with gradient elution and flow rate 0.2 ml/min. Mass detection was Waters Xevo TQD with positive electrospray ionization (ESI) for 6-MP, 6-MMP and negative ESI for 5-FU in multiple reaction monitoring modes. The ions of 6-MP was detected at m/z 153.09->119.09, 6-MMP at m/z 167.17->126.03, and 5-FU at m/z 129.15->42.05. Results: This method fulfill the requirements of selectivity, linearity, lower limit of quantification, accuracy, precision, carry-over, matrix effects, and stability which refers to the european medicines agency (EMEA) guidelines. The linearity of 0.99 was 26-1000 ng/mL for 6-MP and 6-MMP, respectively. The validated method was applied to two childhood ALL maintenance phase. Retrieved 6-MP levels of 10.37 pmol/8×108 erythrocytes, respectively. The levels of 6-MMP gained 16.59 pmol/8×108 erythrocytes, respectively. Conclusion: The developed LC/MS-MS method is valid to analysis 6-MP and 6-MMP in DBS simultaneous in vitro according to EMEA guidelines. The method was successfully applied to authentic capillary blood samples from two childhood patients with ALL in the maintenance phase. Keywords: 6-mercaptopurine, 6-methylmercaptopurine, Dried blood spots, Acute lymphoblastic leukemia.

Item Type: Article
Subjects: Fakultas Agama Islam > RS Pharmacy and materia medica
Depositing User: admin repository uhamka
Date Deposited: 10 Oct 2017 10:03
Last Modified: 10 Oct 2017 10:47
URI: http://repository.uhamka.ac.id/id/eprint/346

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