Quantitation and validation of cis-camphoric acid 3-methyl ester and cis-camphoric acid 1-methyl ester using CE

The 1- and 3-methyl esters of cis-camphoric acid, the active agents of a mi ld laxative (Flubilar(TM)) have been simultaneously assayed using capillary electrophoresis (CE). The compounds are completely separated using a sodiu m acetate buffer pH 4.0, 40 mmol/l. In order to obtain reproducible results , [+]-naproxen has been used as internal standard (IS). Initially migration times changed over 50% within a series of 20 runs. This problem has been o vercome by using an overnight capillary preconditioning (1 mol/l NaOH, 1.5 h) and subsequent equilibrating (running buffer, 12 h). Thereby a precision corresponding to a CV % of about 1.17 and 1.42 for the cia-camphoric acid methyl esters has been obtained (six series of n = 10 runs each). The metho d has been validated regarding specificity, accuracy, precision, linearity and robustness. In order to test robustness, all key parameters have been c onsidered. The result of the validation is given in nine tables. In the cas e under investigation, lamp age and wavelength accuracy are the most critic al parameters. Therefore, the lamp age should be limited to about 1000 h. T he wavelength accuracy can be indirectly controlled using quality assurance samples. According to the fundamental mechanisms in CE, changes in the vol tage and in the temperature influence migration times and peak areas. Howev er, these effects are very well compensated using an IS. Slight variations of the parameters buffer pH and molarity rinsing times, storage conditions of buffers and samples as well as the capillary material had little or no i nfluence on the analytical results. (C) 2000 Elsevier Science B.V. All righ ts reserved.