Self-initiated and concentration-dependent degradation of tetracaine in neat standard solutions: A trouble-shooting story

• Successful trouble-shooting for an interesting and unusual stability case.
• Analyte instability in neat solutions only at high concentrations, not at lower ones.
• Stable-isotope labeled internal standard did not have the similar stability issue.
• Generally applicable insights provided for avoiding neat solution stability issues.

This paper presents the trouble-shooting for a very unusual stability case. Tetracaine was found unstable in neat solutions only at high concentrations, but not at low concentrations. Moreover, its stable-isotope labeled internal standard did not show similar behavior. A series of trouble-shooting experiments were conducted to uncover the root cause. Some generally applicable precautions/insights can be drawn from this investigation to avoid potential stability issues during bioanalytical method development and validation.