Carryover issues in LC-MS analysis of 1,3-diphenylguanidine (DPG) may arise due to strong adsorption to tubing, insufficient needle washing, or retention in the column. To minimize carryover, optimize the needle wash solution using a mix of strong organic solvents (e.g., methanol, acetonitrile, IPA) with additives like formic acid or ammonium hydroxide. Increase flush volumes and needle rinses in the autosampler. Adjust mobile phase composition by incorporating modifiers to improve elution. Perform gradient washes and strong post-run column flushing to remove residual DPG. If adsorption persists, consider using PEEK tubing instead of stainless steel and switching to a different stationary phase.

An additional note on the above comment: Consider checking your gradient elution method. If it does not go 100% organic, it sometimes fails to elute highly organic compounds.

Looking at the physical/chemical properties of DPG, it doesn't seem highly hydrophobic (logP around 2.4, low water solubility) to be absorbed into the system's flow path.

Try an isocratic mobile phase mode, e.g. 40% ACN in H2O with 0.1% formic acid, with a vial content of the same solution. If the carry over was still present, then its an LC issue rather than methodology, thus try different columns/tubing/needle washing procedures.

Thank you all for the thoughtful responses. After considerable effort, I was able to eliminate the carryover issue. Increasing the needle rinsing volume and reducing the maximum working concentration to 100 ppb effectively resolved the problem.