A novel, widespread impurity in mass-compounded tirzepatide/B12 products: potential patient safety implications

BACKGROUND: Compounded versions of tirzepatide are widely available in the U.S. in the form of fixed‑dose combinations of tirzepatide and various analogs of vitamin B12. These combinations are mass marketed in the U.S. and other countries as comparable to FDA‑approved tirzepatide products even though they undergo no evaluation of their potency or impurity profiles. RESEARCH DESIGN AND METHODS: Samples of compounded tirzepatide combined with B12 obtained from various sources in the U.S. market were tested using various analytical methods. Samples were assessed for unacceptable levels of peptide-related impurities. RESULTS: Our testing identified a widespread and previously unidentified impurity in compounded tirzepatide-B12 products resulting from a chemical reaction between tirzepatide and certain analogs of B12. CONCLUSION: Despite the presence of this impurity, these products continue to be mass marketed as 'personalized' treatments. Our findings underscore the importance of testing and FDA approval before new drugs are marketed and highlight potential risks for patients associated with untested combinations. A novel impurity, present at substantial levels in compounded tirzepatide/B12 products, highlights risks inherent in marketing complex therapies outside the drug‑approval framework. Although clinical effects of this impurity are unknown, the identification of a widespread impurity adds to the existing quality concerns presented by compounded tirzepatide.