The utility of sulfonate salts in drug development.
The issue of controlling genotoxic impurities in novel active pharmaceutical ingredients (APIs) is a significant challenge. Much of the current regulatory concern, has been focused on the formation and control of genotoxic sulfonate esters. This is linked with the withdrawal of Viracept (Nefinavir mesilate) from European markets in mid-2007, over concerns about elevated levels of ethyl methanesulfonate (EMS). This issue has resulted in calls from European regulators to assess risk mitigation strategies for all marketed products employing a sulfonic acid counter-ion to ensure that the sulfonate esters that could be potentially formed are controlled to threshold of toxicological concern (TTC)-based limits. This has even led to calls to avoid sulfonic acids as salt counter-ions. However, sulfonic acid salts possess a range of properties that are useful to both synthetic and formulation chemists. Whilst sulfonate salts are not a universal panacea to some of the problems of salt formation they do offer significant advantages as alternatives to other salt forming moieties under certain circumstances. This review thus sets out to define some of the advantages provided through utilization of sulfonic acids, explaining the importance of their retention as part of a thorough salt selection process.
Elder
David P
DP
GlaxoSmithKline Research and Development, Park Road, Ware, Hertfordshire SG12 0DP, United Kingdom. david.p.elder@gsk.com
Delaney
Ed
E
Teasdale
Andrew
A
Eyley
Steve
S
Reif
Van D
VD
Jacq
Karine
K
Facchine
Kevin L
KL
Oestrich
Rolf Schulte
RS
Sandra
Patrick
P
David
Frank
F
D000818:Animals; D055808:Drug Discovery; D006801:Humans; D012492:Salts / Q000737:chemistry* / Q000494:pharmacology; D013451:Sulfonic Acids / Q000737:chemistry* / Q000494:pharmacology
D012492:Salts; D013451:Sulfonic Acids