Chemical purity and mutagenicity: Case study of a drug in development

Kropko, M.L.; Jaen, JC; Theiss, J.C.; Wold, Svante; Caprathe, B.W.; Wise, Lawrence D.

doi:10.1016/0165-7992(92)90014-9

Cited by 4 publications

(2 citation statements)

References 5 publications

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“…[32] 2-Aminothiazolo[4,5-f]quinoline and its 8,9-dihydro derivative showed mutagenic activity in Salmonella typhimurium strain TA-1538. [33,34]…”

Section: Thiocyanation Of Aminoquinolines To Construct Thiazoloquinol...mentioning

confidence: 99%

Synthesis of Thiazoloquinolines with Diverse Molecular Skeletons: A Review

Karmakar

2023

ChemistrySelect

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Thiazoloquinolines are an important class of heterocyclic molecules having a wide variety of biological activities. Since the first synthesis of this fused heterocyclic ring system in 1937, quite a good number of research works have been accomplished in designing and achieving the synthesis of various substituted thiazoloquinolines. These molecules possess diverse structural features and bioactive potentials. A thorough survey of literature, available in this field, clearly indicates that there are certain fused thiazoloquinolines whose syntheses have been largely dealt with while the synthesis of some other fusion pattern remains comparatively less explored. The objective of this review is to present a concise overview of the methods towards the synthesis of thiazoloquinolines in a chronological manner.

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“…[32] 2-Aminothiazolo[4,5-f]quinoline and its 8,9-dihydro derivative showed mutagenic activity in Salmonella typhimurium strain TA-1538. [33,34]…”

Section: Thiocyanation Of Aminoquinolines To Construct Thiazoloquinol...mentioning

confidence: 99%

Synthesis of Thiazoloquinolines with Diverse Molecular Skeletons: A Review

Karmakar

2023

ChemistrySelect

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“…The presence of low-level genotoxic impurities in pharmaceutical products has been documented (1)(2)(3)(4). These are often chemical reagents used in the synthetic process (5) or low-level contaminants generated during synthesis (6). The pharmaceutical industry recognizes the importance of limiting exposure to genotoxic impurities and takes measures to control these impurities during development.…”

Section: Introductionmentioning

confidence: 99%

Low Level Determination of 4-Amino-2-Ethoxy-Cinnamic Acid and its Ethyl Ester in a Drug Substance and its Formulation Prototypes by HPLC--UV-DAD

Soman

Jacob

Swanek

2009

Journal of Chromatographic Science

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A reversed-phase high-performance liquid chromatographic method (HPLC) with diode-array detection (DAD) has been evaluated for monitoring trace levels of impurities, such as 4-amino-2-ethoxy-cinnamic acid (impurity A), hydrochloride salt of 4-amino-2-ethoxy-ethyl cinnamate (impurity B), and 4-bromo-3-ethoxy-nitrobenzene (impurity C), in drug substance and 3 different formulation prototypes. These compounds have been highlighted as potential genotoxins and 2-ethoxy-4-amino-cinnamic acid (impurity A) as possible degradant isolated during the synthesis of BI drug substance. HPLC-UV-DAD was found to be more promising, and limits of quantification were between 0.09 and 0.6 microg/mL, which enabled detection limits in drug substance at 2-15 ppm for a 15 mg/mL solution. All three genotoxic impurities are completely resolved from each other as well as from diluent peaks, drug substance, and other related impurities within 40 min. The retention times of impurities A, B, and C were 3.4, 13.1, and 21.3 min. The results demonstrating the specificity, assay precision, recovery, linearity, and range achieved during the method validation experiments are presented in this paper.

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