Preparation of 4,4′-(1-[2H6]methylethylidene)bis-[2,3,5,6-2H4]phenol and its application to the measurement of bisphenol A in beverages by stable isotope dilution mass spectrometry

The preparation of 4,4'-(1-[H-2(6)]methylethylidene)bis-[2,3,5,6-H-2(4)]phenol, bisphenol A-d(14), was achieved in excellent yield by reaction of [H-2(6)]acetone with [H-2(6)]phenol in the presence of deuterium chloride. The product thus obtained was shown by mass spectroscopy to be a mixture of the H-2(14), H-2(13) and H-2(12) isotopomers in the relative proportions of 82.3:16.2:1.5, respectively. An isotope dilution gas chromatography-mass spectrometric method using bisphenol A-d(14) as an internal standard was developed to measure the level of bisphenol A in beverages. The procedure involves extracting bisphenol A into dichloromethane, and then purifying the analyte by back extraction into dilute aqueous sodium hydroxide. Conversion of bisphenol A and its internal standard, bisphenol A-d(14), to their corresponding O-bis(trifluoroacetyl) derivatives by treatment with trifluoroacetic anhydride gave compounds with good chromatographic properties and whose mass fragmentomerty is such that loss of M-CH3 and M-(CH3)-H-2 are the base peaks in the mass spectra of the analyte and internal standard, respectively. Quantification of bisphenol A was achieved by comparing the area of the M-15 ion to that of the corresponding ion of bisphenol A-d(14). The characteristics of our assay are: an analyte recovery of better than 95%, a root mean square signal-to-noise ratio of 79:1 for 1.7 pg on column and an inter-assay RSD of better than 4% (n=5). (C) 2000 Elsevier Science B.V. All rights reserved.