Gas Chromatography–Mass Spectrometry Combined with Successive Dilution for the Determination of Preservatives in Pharmaceuticals

Some aspects of sample pretreatment and instrumental approaches for the quantification of sorbic acid ( SA ), benzoic acid ( BA ), methylparaben ( MP ) and propylparaben ( PP ) in pharmaceutical and cosmetic samples have been investigated. The proposed method is based on derivatization with isobutyl chloroformate ( iBCF ), application of dispersive liquid−liquid microextraction ( DLLME ) analogue (e.g., ternary-mixture extraction) and gas chromatography−mass spectrometry ( GC−MS ) detection. Fast automated scan/SIM type ( FASST ), a mass acquisition that gives scan and SIM data simultaneously, was applied to target analytes and to detect unknown compounds in real samples. The variables influencing iBCF derivatization and DLLME-analogue extraction were reliably optimized. The optimal conditions were achieved by performing acylation derivatization with 30 µL of iBCF, 30 µL of pyridine and 150 µL of ethanol. The derivatives were then recovered by performing DLLME-analogue with 1 mL of CHCl 3 . After centrifugation, the organic volumes (cloudy phase) of 1 µL were injected into the GC–MS. By applying an external calibration, the developed method was linear in the range of 0.001–100 µg/mL with correlation coefficient values of 0.9988, 0.9973, 0.9996 and 0.9999 for SA, BA, MP and PP, respectively. The detection limit of 0.001–0.01 µg/mL with signal-to-noise more than 3 was obtained for all target analytes. The application of the developed method resulted in accuracy (recovery, %) and precision (RSD) of 75–112% and 2.8–11%, respectively. In summary, the present work describes a developed method for detecting SA, BA, MP and PP in pharmaceuticals and cosmetics using a GC−MS (FASST) approach in combination with a two-step derivatization approach in the aqueous phase, confirming that the method is potential, reliable and valuable in qualitative and quantitative monitoring schemes.