BOX-BEHNKEN DESIGN FOR THE OPTIMIZATION OF SYNTHESIS IMPURITIES B AND E OF ALLOPURINOL

Thien Phuc Lu1,, Thi Kim Tuyen Cao1, My Han Nguyen 1, Manh Quan Nguyen 1, Ngoc Tuyen Truong2, Viet Hung Tran 3, Đuc Tuan Nguyen 2
1 Can Tho University of Medicine and Pharmacy
2 University of Medicine and Pharmacy at HCMC
3 Institute of Drug Quality Control Ho Chi Minh city

Main Article Content

Abstract

  Background: Synthetic impurities B and E of allopurinol are important in the field of drug quality control. However, at present, there are no domestic and foreign studies on the optimization of impurities B and E of allopurinol. The current synthesis processes are not high efficiency, so the application in practice is limited. Survey research and optimize reaction parameters in the impurities B and E synthesis process to increase synthesis efficiency, conduct product purity testing by HPLC-DAD technique towards establishing reference substances.  Survey research and optimize reaction parameters in the synthesis of impurities B and E to increase synthesis efficiency by Box-Behnken model, conduct product purity testing by HPLC-DAD aims to establish a reference substance. Objectives: Survey and optimize the impurities B and E synthesis process of allopurinol. Materials and methods: impurities B and E of allopurinol; Method: Optimizing the impurities B and E synthesis process of allopurinol by Box-Behnken design. Results: The main factors affecting the synthesis efficiency are the number of moles of substances involved in the reaction, the temperature and the time, and the remaining factors are fixed. Determining optimal parameters by Box-Behnken design; impurity B: the mole ratio A/formamide (1/35), number of moles of formamide (0.1 mol), temperature (95oC), time (60 minutes) for highest efficiency; impurity E: the mole ratio D/ formic acid: 23/1891, volume of formic acid (10 mL), temperature (90°C), time (4 hours) for the highest efficiency. Conclusions: Experimental design based on BoxBehnken design and optimized by JMP 13.0 software help assess the impact of factors on the yield synthesis and predict the optimal reaction parameters.

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References

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