EVALUATION OF DIFFERENT INJECTION TECHNIQUES IN THE GAS-CHROMATOGRAPHIC DETERMINATION OF THERMOLABILE TRACE IMPURITIES IN A DRUG SUBSTANCE

Thermodegradation of labile compounds in the hot injection port of a g as chromatograph causes many problems and can lead to ambiguous, poorl y reproducible results. Splitless injection used in trace analysis in order to achieve a lower detection limit may even enhance the difficul ties due to the longer residence time of the volatized sample in the i njection port, Different techniques were tested to avoid thermodegrada tion of an epoxide and its corresponding chlorohydrin in a drug substa nce: variation of the injector temperature, high inlet flow rate durin g injection by electronic pressure programming, and cool on-column inj ection. The results showed that on-column injection was superior to sp litless injection. The chlorohydrin formed epoxide by release of HCl u pon splitless injection. A more detailed investigation of the factors that affect epoxide formation indicates that active sites within the i njector are responsibile for the degradation and that the reaction is temperature dependent. However, results equivalent to those obtained b y on-column injection were obtained for splitless injection when inert materials were used in the injector.