CHROMATOGRAPHY, Vol. 25 (2004), No. 2, pp. 61-65

Liquid chromatography/mass spectrometry (LC/MS) operating condition and the sample preparation method were developed and fully validated according to the guidelines issued by Internal Conference on Harmonization (ICH) for the determination of (R ).3.chlorostyrene oxide (RCSO) present in bulk chemicals. RCSO is the raw material of a certain promising medical chemical. The chromatographic separation of RCSO and bulk chemical was achieved using a mixture of methanol and acetate buffer (3:2) as the mobile phase. Mass spectrometric analysis was performed by atmospheric pressure chemical ionization (APCI) mode with positive ion detection. Single ion monitoring (SIM) scan mode of m/z 172.1 was used to quantitatively determine RCSO. Analysis by LC/APCI.MS was carried out within 10 min. Limits of detection and quantitation level of RCSO in bulk chemicals were estimated to be 5 and 10 ng/mg chemical corresponding to 5 ppm and 10 ppm, respectively. Calibration curve of RCSO exhibited the linearity in the RCSO concentration of 10.120 ng/mg chemical (ppm). Accuracy and intermediate precision of this method were 0.4% and 2.8%, respectively. This analytical method as the impurity testing for quality control was successfully applied to bulk chemicals. RCSO was not detected at all in 32 batches of bulk chemicals tentatively manufactured in our laboratory.