Genotoxic Impurities in Pharmaceuticals

Jouyban, Abolghasem; Parsa, Hamed

doi:10.5772/24030

Cited by 7 publications

(4 citation statements)

References 71 publications

(113 reference statements)

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“…The presence of benzaldehyde in the mentioned solvent mixture has a strong influence on the occurrence of side reactions, such as formations of hydrates, acetals and hemiacetals [4]. Its reactivity could additionally lead to formation of several GTIs, such as benzohydrazide, 1-benzoyl-2-[(4RS)-1-methylhexahydro-1-hazepin-4yl] diazane, aryl hydrazones, 4-hydrazine benzene sulfonamide, and so on [16].…”

Section: Introductionmentioning

confidence: 99%

Removal of benzaldehyde from a water/ethanol mixture by applying scavenging techniques

Mitić

Skov²,

Gernaey

2016

Green Processing and Synthesis

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A presence of carbonyl compounds is very common in the food industry. The nature of such compounds is to be reactive and thus many products involve aldehydes/ketones in their synthetic routes. By contrast, the high reactivity of carbonyl compounds could also lead to formation of undesired compounds, such as genotoxic impurities. It can therefore be important to remove carbonyl compounds by implementing suitable removal techniques, with the aim of protecting final product quality. This work is focused on benzaldehyde as a model component, studying its removal from a water/ethanol mixture by applying different derivatization agents as the scavengers. Discovery chemistry is performed in the beginning as a screening procedure, followed by the process design of a small-scale continuous process for benzaldehyde removal with in-line real-time monitoring. Applications of tris(hydroxymethyl)aminomethane (TRIS) are found to provide above average removal of benzaldehyde.

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Section: Introductionmentioning

confidence: 99%

Removal of benzaldehyde from a water/ethanol mixture by applying scavenging techniques

Mitić

Skov²,

Gernaey

2016

Green Processing and Synthesis

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“…the spindle apparatus) or enzymes (e.g. topoisomerases) are designated genotoxic (Dearfield et al 2002;Robinson 2010;Jouyban and Parsa 2012). Genotoxicity is sometimes associated with cancer.…”

Section: Introductionmentioning

confidence: 99%

A review of the genotoxic and carcinogenic effects of aspartame: does it safe or not?

Yılmaz

Uçar

2014

Cytotechnology

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The objective of this article is to review genotoxicologic and carcinogenic profile of the artificial sweetener aspartame. Aspartame is a synthetic dipeptide, nearly 180-200 times sweeter than sucrose. It is the most widely used artificial sweetener especially in carbonated and powdered soft drinks, beverages, drugs and hygiene products. There is a discussion ongoing for many years whether aspartame posses genotoxic and carcinogenic risk for humans. This question led to many studies to specify the adverse effects of aspartame. Therefore, we aimed to review the oldest to latest works published in major indices to gather information within this article. With respect to published data, genotoxicity and carcinogenicity of aspartame is still confusing. So, consumers should be aware of the potential side effects of aspartame before they consume it.

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“…First, ever since the “bad smell” incident of Viracept in 2007, mesylate salts in general have become somewhat a taboo in the industry because of the potential genotoxicity concern of mesylate esters such as methyl or ethyl methanesulfonate (EMS). Although this topic has been thoroughly studied, the industry has generally been cautious of mesylate salts unless tight control of mesylate ester impurities can be implemented. Second, profound polymorphism has already manifested for KO-947 mesylate salt with four forms identified during the initial screen.…”

Section: Resultsmentioning

confidence: 99%

Solid Form Selection and Process Development of KO-947 Drug Substances

Meng

Zhu

Guo

et al. 2021

Org. Process Res. Dev.

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KO-947 is a potent, selective extracellular signal-regulated kinases (ERK) inhibitor that was investigated in the clinic for the treatment of various solid tumors. KO-947 free base, form E, was originally recommended out of 10 identified crystalline forms for the development of an oral solid dosage product. Change of clinical need shifted the focus to aqueous solubility enhancement through salt formation. Mesylate salt demonstrated remarkably increased aqueous solubility and also profound polymorphism. Anhydrous form III was initially recommended but later dropped, primarily due to the manufacturing difficulties. In the end, form IX was discovered through close collaboration between preformulation and process scientists. An elaborate manufacturing process was then devised to successfully produce mesylate salt, form IX in kilogram scale supplied for the clinical use.

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Genotoxic Impurities in Pharmaceuticals

Cited by 7 publications

References 71 publications

Removal of benzaldehyde from a water/ethanol mixture by applying scavenging techniques

Removal of benzaldehyde from a water/ethanol mixture by applying scavenging techniques

A review of the genotoxic and carcinogenic effects of aspartame: does it safe or not?

Solid Form Selection and Process Development of KO-947 Drug Substances

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