This recent letter in Antimicrobial Agents and Chemotherapy from authors from Paratek Pharma on the purity and/or stability of commercially purchased omadacycline tosylate was of interest. Omadacycline is a semi-synthetic tetracycline derivative approved for the treatment of bacterial infections (CABP and CSSSI). In this study, powder from a commercial vender was found to ~53% (wt/wt) omadacycline tosylate when compared to the authentic Paratek omadacycline tosylate drug substance. The purchased material was also amorphous and not crystalline. The remaining material was composed primarily of known impurities without microbiological activity. While this could change an MIC one-fold (not ideal), it could have consequences in other studies.

In another recent publication in Journal of Pharmaceutical and Biomedical Analysis, which was recently discussed by Derek Lowe, workers at Genentech highlighted the importance of investigating drug substance mass balance. They found that azetidine oligomers were present in the drug batch that were not observable by standard NMR, LC, ICP and GC methods. Metal impurities also well known and can cause issues in bioassays, potential toxicity and cause mayhem with drug batch reproducibility.

The most egregious issues can occur when the compound label does not correspond to what’s in the container. Probably the most (in)famous case was when an MDMA (‘ecstasy’) bottle was mislabelled as methamphetamine. This led to a 2003 retraction of a 2002 Science paper that initially claimed that MDMA was as toxic to primates as methamphetamine (also see commentary). There are also residual effects of the initial reports, as the retraction was not as visible in mainstream newspapers – see this article in Journal of Psychoactive Drugs. If you want to delve deeper, Retraction Watch has a specific category devoted to ‘wrong reagents’.

So, it’s always advisable to look for data anomalies, even if they are slight. Also, don’t 100% rely on what is written on the label.