Evaluation of Solvent Compatibilities for Headspace-SIFT-MS Analysis of Pharmaceutical Products

Procedures for determination of the residual solvent and volatile impurity content in pharmaceutical products usually rely on dissolution a solvent, followed by headspace-gas chromatography (HS-GC) analysis. Whereas chromatographic systems can utilize wide variety solvents, direct-injection mass spectrometry (DIMS) techniques have fewer options, because elimination column means that instrument is more susceptible to saturation. Since water has lowest impact, it almost always been default DIMS. In this study, selected ion flow tube (SIFT-MS)—a DIMS technique—was applied systematic evaluation proportion be utilized (with aqueous diluent) without causing saturation while maintaining satisfactory analytical performance. The solvents evaluated were N,N-dimethylacetamide (DMAC), N,N-dimethylformamide (DMF), 1,3-dimethyl-2-imidazolidinone (DMI), dimethyl sulfoxide (DMSO), methanol, triacetin. All are compatible with headspace-SIFT-MS analysis at 5% (min) water, DMI, DMAC, DMSO used higher concentrations (50, 100, 25%, respectively), though suffering substantial diminution limit quantitation non-polar analytes proportions non-aqueous solvent. Analytical performance was also using linearity, repeatability, recovery measurements. This work demonstrates organic diluted provide an approach additional diluent solvents.