title: Determination of the chemical constituents and spectral properties of commercial and NF reference standard potassium guaiacolsulfonate: implications of the findings on compendial analytical methodology.
abstract: HPLC analysis confirmed a difference in the chemical composition of commercial versus NF reference standard potassium guaiacolsulfonate. After separation by fractional crystallization, the two constituents comprising the former sample were identified by 1H-NMR as potassium guaiacol-4- and -5-sulfonate, respectively. The former isomer predominated. The reference standard material was identified as the 4-sulfonate salt by HPLC, NMR, IR, and UV. This difference raises questions concerning the validity of the compendial identification tests and assay procedure for the drug, which are based on methods requiring direct comparison between it and the reference standard. In fact, the IR test has now been shown to be unreliable as a rigorous criterion for identification, in light of significant differences found in the fingerprint regions of the spectra of the two isomers. However, because the two isomers exhibit identical UV absorption characteristics in solutions of pH less than or equal to 7 (but not in alkaline solution), the compendial UV identification test and assay procedure appear to be valid under the conditions specified. The pKa values of the isolated isomers were estimated by a spectrophotometric method to be 8.74 and 9.16 for the phenolic group of potassium guaiacol-4- and -5-sulfonate, respectively.
mesh_terms: D000107:Acetylation; D002851:Chromatography, High Pressure Liquid; D003460:Crystallization; D005569:Formularies as Topic; D006139:Guaiacol / Q000031:analogs & derivatives* / Q000032:analysis / Q000592:standards; D007536:Isomerism; D009682:Magnetic Resonance Spectroscopy; D012015:Reference Standards; D013055:Spectrophotometry, Infrared; D013056:Spectrophotometry, Ultraviolet; D014481:United States
chemical_list: C013710:guaiacolsulfonic acid; D006139:Guaiacol