Integrating UPLC‐QTOF‐MS/MS and UPLC‐DAD to evaluate the influence of sulfur‐fumigated Paeoniae Radix Alba on the overall quality of three Si‐Wu‐Tang formulations

Abstract Introduction Sulfur‐fumigation of Paeoniae Radix Alba (PRA) could induce the chemical transformation of its bioactive component paeoniflorin into a sulfur‐containing derivative paeoniflorin sulfite, and thus alter the quality, bioactivities, pharmacokinetics, and toxicities of PRA. However, how sulfur‐fumigated PRA (S‐PRA) affects the quality of PRA‐containing complex preparations has not been intensively evaluated. Objectives We intend to evaluate the influence of S‐PRA on the overall quality of three kinds of Si‐Wu‐Tang (SWT) formulations, i.e., decoction (SWT‐D), granule (SWT‐G), and mixture (SWT‐M). Material and Methods An UPLC‐DAD multi‐components quantification method was used to compare the transfer rates of paeoniflorin sulfite and other 10 bioactive components between S‐PRA‐containing and NS‐PRA‐containing SWT formulations. An UPLC‐QTOF‐MS/MS‐based target metabolomics approach was applied to explore the differential sulfur‐containing derivatives in S‐PRA‐containing SWT formulations. Results The transfer rates of paeoniflorin sulfite in three S‐PRA‐containing SWT formulations were all higher than 100%. Moreover, S‐PRA also increased the transfer rate of 5‐hydroxymethylfurfural, 1,2,3,4,6‐ O ‐pentagalloylglucose, whereas decreased that of paeoniflorin, albiflorin, and ferulic acid in three SWT formulations. Six pinane monoterpene glucoside sulfites originally identified in S‐PRA, were also detectable in three S‐PRA‐containing SWT formulations. In addition, seven phenolic acid sulfites including (3Z)‐6‐sulfite‐ligustilide, (3E)‐6‐sulfite‐ligustilide, 6,8‐disulfite‐ligustilide, ferulic acid sulfite, neochlorogenic acid sulfite, chlorogenic acid sulfite, and angelicide sulfite (or isomer) were newly identified in these three S‐PRA‐containing formulations. Conclusion S‐PRA could differentially affect the transfer rate of paeoniflorin sulfite and other bioactive components during the preparation of three SWT formulations and subsequently the overall quality thereof.