Screening commercial available resins for simultaneous removal of two potential genotoxins from API methanolic streams

ABSTRACT

This paper explores potential API loss mitigation during purification in recrystallization mother liquors, by including a resin adsorption step, to remove potential genotoxin impurities (PGTIs). Mometasone furoate (Meta) is used as model active pharmaceutical ingredient (API) in the presence of 4-dimethylaminopyridine (DMAP) and methyl p-toluenesulfonate (MPTS) as two model PGTIs. AG 50W-X2 and IRA68 resins efficiently removed DMAP and MPTS from methanol solutions, respectively, with adsorptions higher than 93% and Meta binding below 2%. Removal of GTIs using these resins sequentially, or combining them in a single step, was also assessed, with superior results for the later approach.

Abbreviations: API, active pharmaceutical ingredient; DMAP, 4-dimethylaminopyridine; DMAP-Me, methylated DMAP; GTI, potential genotoxin impurity; Meta, Mometasone furoate; MPTS, methyl p-toluenesulfonate; PTSA, p-toluenesulfonic acid; TTC, threshold of toxicological concern.

KEYWORDS:

• Potential genotoxin impurity
• resin adsorbents
• 4-dimethylaminopyridine
• methyl p-toluenesulfonate
• active pharmaceutical ingredient purification

Supporting Information

Binding isotherm theoretical model parameters assessed in this report, pH influence on DMAP binding for several resins in water and in water:MeOH (1:1), kinetic profile of DMAP in water towards AG 50W-X2 resin and assessment of DMAP-ME and PTSA in Meta mother liquor by ¹H NMR in MeOH-d₄ can be found in Supporting Information.

Supplemental material

Supplemental data for this article can be accessed here.

Additional information

Funding

This work was supported by the Fundação para a Ciência e Tecnologia (FCT) through the project SelectHost [grant number PTDC/QEQ-PRS/4157/2014]; FCT through the project Genosep [grant number PTDC/QEQ-PRS/2757/2012]; iBB - Institute for Bioengineering and Biosciences [grant number UID/BIO/04565/2013], from Programa Operacional Regional de Lisboa 2020 [grant number Lisboa-01-0145-FEDER-007317]; and from Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq – Brazil).