Detection of Leachables in Huoxiang Zhengqi Liquid Based on Fabric Phase Sorptive Extraction and Their Risk Assessment

KeyWord:pharmaceutical packaging materials  extractables and leachables  fabric phase sorptive extraction£¨FPSE£©  fast screening  risk assessment  ultra-performance liquid chromatography£­tandem mass spectrometry

Abstract:

      A new method for the rapid detection of leachables in Huoxiang Zhengqi liquid was developed by ultra-performance liquid chromatography£­tandem mass spectrometry£¨UPLC£­MS/MS£© with fabric phase sorptive extraction£¨FPSE£©£®The fabric extraction phase was prepared by coating polydimethylsiloxane£¨PDMS£© on the cotton fiber cloth through a sol£­gel reaction£®Effects of extraction time£¬ionic strength£¬type of desorption solution£¬volume of desorption solution and desorption time on extraction efficiency were optimized£®A 2.0 cm ¡Á 2.0 cm fabric extraction phase and magnetic agitator were placed in a 5 mL sample£¬extracted for 30 min at 700 r/min£¬then ultrasonically eluted with 1 mL acetonitrile as the back-extraction solvent for 10 min to obtain the best extraction effect£®The results showed that the calibration curves for the analytes showed good linearity with their correlation coefficients£¨r£© not less than 0.996 1£®The limits of detection£¨LOD£© and limits of quantitation£¨LOQ£© were in the ranges of 0.5£­1.5 ¦Ìg/L and 1.5£­4.0 ¦Ìg/L£¬respectively£®Spiked recoveries for 8 analytes were in the range of 73.8%£­98.2%£¬with relative standard deviations£¨RSD£¬n = 3£© of 0.98%£­8.4%£®In order to simulate the solvent formula of Huoxiang Zhengqi liquid£¬ethanol/water£¨1¡Ã1£© was selected to extract the plastic packaging bottles£®Moreover£¬in order to get a more reliable and comprehensive extractables profile£¬isopropanol was also used as the storage solution to obtain an extremely harsh environment£®The sample was detected by ultra-performance liquid chromatography£­quadrupole time-of-flight mass spectrometry£¨UPLC£­QTOF MS£©£¬and the extractables of the sample were screened through the UNIFI software based on a polymer additive library and online screening£®There were 33 compounds identified£®Then these extractables were targetedly detected in the Huoxiang Zhengqi liquid by UPLC£­MS/MS£®A total of 4 leachables were detected and quantified£®The results of toxicological evaluation based on Toxtree and T.E.S.T software showed that the actual daily intake of the 4 leachables will not exceed the permitted daily exposure£¬indicating that the content of leachables in Huoxiang Zhengqi liquid is relatively safe£®