A General Strategy to Rapid and Sensitive Determination of Five High Boiling Point Solvents in Pharmaceuticals by RP-HPLC Combined with Precipitation Method.

The difficulty on determination of high boiling point solvents, always exist due to their low vapor pressure in headspace (HS) vial. What's worse, the commonly used GC diluents, such as N, N-dimethylacetamide, 1,3-dimethyl-2-imidazolidinone, dimethyl sulfoxide, N, N-dimethylformamide and N-methylpyrrolidone are often remained in HS instrument after frequent injection into HS, thus would result in terrible positive interference problem. In this work, a fast and sensitive HPLC method in combination with a sample precipitation method, was proposed for the determination of above five high boiling point solvents in drug substances within 14.5 min. The final method was validated with regard to limit of detection and limit of quantitation, precision, linearity and accuracy in accordance with ICH Q2 (R1). Finally, the proposed strategy was successfully applied for the analysis of high boiling point solvents used in three active pharmaceutical ingredients. The established generic strategy would provide another choice for the determination of high boiling point solvents in pharmaceuticals.