IMPROVEMENTS IN DRUG PURITY DETERMINATION BY CAPILLARY ELECTROPHORESIS USING UV-ABSORPTION AND LIF-DETECTION WITH A UV-LASER

In drug purity determinations by capillary electrophoresis using UV-de tection generally a relative high concentration of the main compound h as to be injected. Principles how to handle overloading effects are de scribed. NXX-066 is a drug with a native fluorescence which made it po ssible to use a CE system equipped with a LIF-detection unit. Monitori ng drug purity determination with LIF detection results in an improved limit of quantification of the impurities and/or opens a possibility to avoid an overloaded main peak. A frequency doubled (FRED) argon ion laser set at 244 nm was used as excitation source in drug purity dete rmination with the LIP-detection unit and the chemicals used were ther efore carefully chosen in order to minimize the background noise level , which easily is enhanced when fluorescence detection is performed in the UV-range. The separation of the fluorescent NXX-066 analogues pro ved to be a difficult task, but an adequate resolution was obtained wh en beta- and gamma-cyclodextrins was added as structural selectors and the separation window was expanded by the use of a repressed/reversed electroosmotic flow. A comparison of the separation capability for th e UV-detection system and the laser induced fluorescence detection sys tem was performed, showing that the overloading effects of the main pe ak can be removed using the CE-LIF system and thereby obtain a substan tially improved resolution of the analogues. A comparison of LC-UV and CE-UV for drug purity determination of a crude product from synthesis of NXX-066 is also included in this paper where a good correlation of the results were obtained.