Analytical method development for a specific assay method for monomethoxypoly(ethylene glycol)succinimido carbonate...

Three different quantitative methods, which rely on base-mediated reactions for the purity assessment of the hydrolytically unstable activated ester, mPEG-SC (1) are discussed. In a spectrophotometric assay, controlled base-catalyzed hydrolysis of mPEG-SC (1) affords N-hydroxysuccinimide and its concentration can be determined by UV analysis. Reaction of mPEG-SC (1) with benzylamine and a non-aqueous back titration of the remaining benzylamine can also be used for purity determination of mPEG-SC (1). HPLC analysis of derivatized forms of mPEG-SC (1) affords a potential specific assay for these polymers. The relative attributes and shortcomings of these methods are elaborated. Although the titration assay is intermediate in specificity, the greater precision of the method makes it the preferred method at this stage of development of an HPLC-ELSD or HPLC-UV assay method. The percent relative standard deviation (%R.S.D.) of the titration method was 2.9% as opposed to 8.8% for the HPLC assay. The accuracy of the titration method was shown to be 101+/-4.0% and was sufficient to justify a blending operation according to FDA cGMP guidelines.