HPCE analysis of hydrolysing morphine derivatives. Quantitation of decomposition rate and mobility

High performance capillary electrophoretic conditions were optimised on the basis of protonation constants and hydrolysis rate constants (if relevant) of 6 opiate compounds. Protonation constants were determined by pH-potenti ometry, the progress of hydrolysis was followed by capillary electrophoresi s, hydrolysis rate constants of ester-type compounds were elucidated by kin etic studies of the time- and pH-dependence of the decomposition. Using the se physico-chemical parameters, the analysis circumstances were designed to keep the in situ hydrolysis rate negligible for every compound, which has not been the case in reported previous HPCE determinations of acetylated de rivatives. Our calculated charge-related mobility differences and experimen tal CZE findings justified those earlier statements that capillary zone ele ctrophoresis is insufficient to separate these compounds. The method develo pment for diacetylmorphine, 3-acetylmorphine, 6-acetylmorphine, morphine, a cetylcodeine and codeine resulted in the use of a micellar electrokinetic s ystem operating at pH = 8.0, applying 50 mM sodium dodecyl sulfate micellef orming agent and 7.5 % acetonitrile additive in the background electrolyte.