Journal of AOAC International

Alternative liquid chromatographic method for determination of the methoxyl and 2-hydroxypropoxyl content in cellulose ether derivatives.

PMID 14509426


An alternative liquid chromatographic (LC) method was developed and validated for the simultaneous determination of methoxyl and 2-hydroxypropoxyl substituents in hypromellose and hypromellose acetate succinate. The method uses the hydriodic acid cleavage reaction, catalyzed by adipic acid, of the substituted methoxyl and 2-hydroxypropoxyl groups, which are quantitatively converted to iodomethane and 2-iodopropane. The iodomethane and 2-iodopropane are extracted into xylene, the extract is diluted with methanol, and the analytes are separated and assayed by gradient elution using a reversed-phase C18 column. The method is selective and sensitive and has good linearity with values of 0.999 for R2 and 0.25% for the gamma-intercept bias from 1.39 to 5.55 mg/mL for iodomethane, and 0.999 for R2 and 0.52% for the gamma-intercept bias from 0.184 to 0.735 mg/mL for 2-iodopropane. The relative standard precisions for this LC method were found to be +/- 2.3% for determining methoxyl at the 23.1% (w/w) level, and +/- 3.5% for determining 2-hydroxypropoxyl at the 6.7% (w/w) level. Compared with the current gas chromatographic (GC) compendial (JPE) method, the LC assay method has equal or better precision. It was found that both the standard and sample solutions have limited stability (8 h) after preparation. This limited stability has not been reported previously in the literature and may have an impact on the reported accuracy/precision of the literature data for the GC method. The LC method was proven to be robust with respect to variation in derivatization time and temperature, flow rate, and column temperature. It is well suited for the quality control needed in today's fast-paced pharmaceutical laboratories.

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2-Iodopropane, contains copper as stabilizer, 99%