(W1130-06-38) Utilizing Organic Solvents for Residual Solvent and Volatile Impurity Analysis of Water-Insoluble Articles Using SIFT-MS

Purpose: Historically water has been the universal solvent for headspace analysis using selected ion flow tube mass spectrometry (SIFT-MS) because certain organic solvents can overload instrumentation. The current work describes the extension of SIFT-MS analysis to accommodate suitable non-aqueous solvents that are necessary for testing water-insoluble articles in residual solvents analysis.

Methods: A SIFT-MS instrument (Syft Tracer; Syft Technologies, Christchurch, NZ) coupled with a GERSTEL MPS Robotic Pro (Mulheim, Germany) was used in this work. Samples were incubated (60 °C for 45 min) in a GERSTEL agitator followed by sampling of an aliquot (2.5 mL) of the headspace using a headspace syringe (heated to 150 °C) and subsequently injection (50 μL s^-1) into the SIFT-MS instrument’s autosampler inlet (heated to 120 °C). Ultra-high pure nitrogen was used as make-up gas flow to ensure that the total flow into the instrument was 25 mL min⁻¹. A systemic evaluation of the compatibility of the following six organic solvents with headspace-SIFT-MS analysis following dissolution and dilution with water was carried out: - N,N-Dimethylacetamide (DMAC), N,N-dimethylformamide (DMF), 1,3-dimethyl-2-imidazolidinone (DMI), dimethyl sulfoxide (DMSO), methanol, and triacetin. Linearity and repeatability measurements on a subset of residual solvents were used to determine the suitability of these on-aqueous solvents' compatibility with SIFT-MS.

Results: Feasibility (relative analyte sensitivity as a function of the proportion of non-aqueous solvent) studies using a fixed analyte concentration indicated that at 5% solvent dilution (across all organic solvents), for most analytes the sensitivity of SIFT-MS remains similar to that of the corresponding aqueous system. It is evident, however, that for DMI, DMSO and DMAC significantly higher proportions are usable. Generally, the non-polar analytes tend to exhibit enhanced retention in solution compared to polar analytes as the organic solvent proportion increases. Linearity (assessed using the regression coefficient, R², of a standard curve plotted using 8 points) of four representative analytes in all 5% solvent-aqueous mixes was excellent overall ( >0.992 for all ions except benzene in DMSO). Repeatability was assessed using six replicates at three concentration levels in all 5% solvent-aqueous mixes. With few exceptions, relative standard deviation (RSDs) across all product ions met general acceptance criteria ( < 20%). A summary of the usable reagent ions, concentration ranges over which the solvent can be used with normal headspace operating conditions, and some solvent-specific comments can be found in Table 1.

Conclusion: SIFT-MS can analyze residual solvents and other volatile impurities in water-insoluble articles using a two-step process: dissolution in a compatible solvent, then dilution in water. The choice of solvents is determined by i) the articles themselves, ii) the partitioning properties of the analytes, and iii) the product ions contributed by the solvent. Quantitative headspace analysis of a wide range of analytes can be achieved in a single analysis using SIFT-MS.

References: Perkins MJ, Silva LP, Langford VS (2023). Extending SIFT-MS residual solvent and volatile impurity analysis to water-insoluble articles. Syft Technologies application note

Solvents compatible with headspace SIFT-MS analysis (with usable reagent ions), upper limit recommended in water, and some practical comments. * Maximum percentage recommended (diluted in water).