New possibilities for pharmaceutical excipients analysis: Combustion combined with pyrohydrolysis system for further total chlorine determination by ICP-OES.

An alternative method for the determination of total chlorine content in hydroxypropyl cellulose (HPC) was applied, combining a recently developed system based on a combustion step followed by pyrohydrolysis reaction. Using this approach it the determination of total chlorine by inductively coupled plasma optical emission spectrometry (ICP-OES) without interferences was feasible. It overcame the limitations of European Pharmacopoeia (EP) method for HPC analysis regarding to the inability to determine total chlorine in HPC, once some chlorine compounds (e.g., chloroform) that can not be identified by the official method (EP). The following parameters of combustion and pyrohydrolysis were evaluated: absorbing solution, sample mass, the use of powdered silica as retardant of combustion, oxygen flow rate and reaction time. Reference values for total chlorine were obtained after digestion using microwave-induced combustion and determination by ion chromatography (IC). Microwave-assisted extraction (MAE) was also investigated for Cl extraction. The accuracy of the proposed method was also evaluated by analyte recovery tests (agreement of 95-103%), as well as by the analysis of certified reference materials (CRMs). The agreement with the certified values was higher than 95% and the limit of quantification (LOQ) was 50 µg g. Up to 500 mg of sample were efficiently digested by the proposed method in 5 min (dissolved carbon in digests was below 50 mg L). Total chlorine content in samples of modified cellulose ranged from 284 to 576 µg g. Despite the relatively high chlorine content in all samples, the concentration was lower than the maximum limit allowed by the EP for HPC (0.5%).