VALIDATION OF 6-MERCAPTOPURINE AND 6-THIOGUANINE IN DRIED BLOOD SPOT BY ULTRA PERFORMANCE LIQUID CHROMATOGRAPHY-TANDEM MASS SPECTROMETRY

Authors

  • Yahdiana Harahap Faculty of Pharmacy, Universitas Indonesia, Depok, 16424, Indonesia.
  • Cheputri Rahma Astrini Faculty of Pharmacy, Universitas Indonesia, Depok, 16424, Indonesia.
  • Herman Suryadi Faculty of Pharmacy, Universitas Indonesia, Depok, 16424, Indonesia.

DOI:

https://doi.org/10.22159/ijap.2018.v10s1.91

Keywords:

6-Mercaptopurine, 6-Thioguanine, Dried blood spot, Ultra-high-performance liquid chromatography-tandem mass spectrometry

Abstract

Objective: This study aimed to obtain an optimal and validated method of analyzing 6-mercaptopurine (6-MP) and 6-thioguanine (6-TG) simultaneously
in dried blood spot samples using ultra high-performance liquid chromatography-tandem mass spectrometry.
Method: Separation was performed with a 1.7-μm amide column, which had a mobile phase with a flow rate of 0.2 mL/min and comprised 0.2%
formic acid in water, 0.1% formic acid in acetonitrile, and methanol with a gradient elution. Detection was performed using Waters Xevo TQD.
Result: This method was linear with a range of 25–1000 ng/mL for 6-MP and 6-TG, with consecutive r values of ≥0.996 and ≥0.995, respectively. The
intra- and inter-day % difference value and coefficient of variation for the accuracy and precision were not more than 15% and 20%, respectively, at
a concentration lower limit of quantitation.
Conclusion: This method fulfilled the requirements of the European Medicines Agency guideline for validation.

Downloads

Download data is not yet available.

References

Lockwood W. Leukemia: AML, CML, ALL and CLL;2015 p. 1-32

from http://WWW.RN.ORG®.

National Cancer Institute. What You Need To Know About Leukemia.

U.S: Department of Health and Human Services; 2015.

Rini TA, Aisyi M, Sari Y, Edi ST. Characteristics of acute lymphoblastics

leukemia in children at dharmais cancer hospital 2000 – 2008. Ind J

Cancer 2009;4:137-40.

Katzung BG. Basic and Clinical Pharmacology. 10th ed. USA: McGraw-

Hill; 2007.

Polifka J, Friedman J. Teratogen update: Azathioprine and 6-mercaptopurine.

Teratology 2002;65:240-61.

Su Y, Hon YY, Chu Y, Van de Poll ME, Relling MV. Assay of

-mercaptopurine and its metabolites in patient plasma by highperformance

liquid chromatography with diode-array detection.

J Chromatogr B Biomed Sci Appl 1999;732:459-68.

Al-Ghobashy MA, Hassan SA, Abdelaziz DH, Elhosseiny NM, Sabry NA,

Attia AS, et al. Development and validation of LC-MS/MS assay for

the simultaneous determination of methotrexate, 6-mercaptopurine and

its active metabolite 6-thioguanine in plasma of children with acute

lymphoblastic leukemia: Correlation with genetic polymorphism.

J Chromatogr B Analyt Technol Biomed Life Sci 2016;1038:88-94.

European Medicines Agency. Guideline on Bioanalytical Method

Validation. Available from: http://www.ema.europa.eu/docs/en_GB/

document_library/Scientific_guideline/2011/08/WC500109686.pdf.

[Last accessed on 2015 Oct 12].

Wagner M, Tonoli D, Varesio E, Hopfgartner G. The use of mass

spectrometry to analyze dried blood spots. Mass Spectrom Rev

;35:361-438.

Zochowska D, Zegarska J, Hryniewiecka E, Samborowska E,

Jazwiec R, Tszyrsznic W, et al. Determination of concentrations of

azathioprine metabolites 6-thioguanine and 6-methylmercaptopurine

in whole blood with the use of liquid chromatography combined with

mass spectrometry. Transplant Proc 2016;48:1836-9.

Patel D. Matrix effect in a view of LC-MS/MS: An overview. Int J

Pharm Bio Sci 2011;2:559-64.

Potawale RS, Gilhotra RM, Gabhe SY. Liquid chromatography tandemmass

spectrometry method development and validation for simultaneous

analysis of paracetamol, guaifenesin, phenylephrine hydrochloride,

chlorpheniramine maleate, and ambroxol hydrochloride in bulk and in

tablet dosage form. Asian J Pharm Clin Res 2018;11:375-82.

Srikanth I, Prameela RA. Development and validation of liquid

chromatography coupled with tandem mass spectrometry method for

estimation of lenvatinib in human plasma. Asian J Pharm Clin Res

;10:120-6.

Alvi SN, Hammami MM. Measurement of cortisol in human plsma

and urine by ultra performance liquid chromatography-tandem mass

spectrometry. Asian J Pharm Clin Res 2018;11:199-203.

Published

20-12-2018

How to Cite

Harahap, Y., Astrini, C. R., & Suryadi, H. (2018). VALIDATION OF 6-MERCAPTOPURINE AND 6-THIOGUANINE IN DRIED BLOOD SPOT BY ULTRA PERFORMANCE LIQUID CHROMATOGRAPHY-TANDEM MASS SPECTROMETRY. International Journal of Applied Pharmaceutics, 10(1), 412–415. https://doi.org/10.22159/ijap.2018.v10s1.91

Issue

Section

Original Article(s)