Analysis of 21 phthalate leachables in metered dose inhalers by gas chromatography tandem mass spectrometry

Abstract

For the first time, a gas chromatography tandem mass spectrometry method in the multiple reaction monitoring mode was developed and validated for the separation and detection of 21 phthalate leachables in meter dose inhalers (MDI). The optimized method was reliable with high sensitivity and selectivity. Calibration curves were linear with correlation coefficients (R²) > 0.990, and limit of detection (LOD) values in the range of 0.1–4.2 ng mL⁻¹ except for di(2-methoxyethyl) phthalate, di(2-ethoxyethyl) phthalate and di(2-n-butoxyethyl) phthalate, for which the LODs were around 10 ng mL⁻¹. Recoveries ranged between 86.6 and 108.3%, and the relative standard devision values of precision were within 7.72%. For the five MDI batches analyzed, 5 out of 21 phthalates were detected in each sample, including dimethyl phthalate, diethyl phthalate, diisobutyl phthalate, dibutyl phthalate and di(2-ehtylhexyl) phthalate, with total phthalate amounts of less than 260 ng per canister.