| Abstract [eng] |
Organic residual solvents can be unavoidable in pharmaceutical industry, even after drying, due to the organic solvents presence in many manufacturing steps. These ORSs can present many harmful effects which need to be avoided. Consequently, the presence of ORSs in pharmaceuticals is being strictly regulated by pharmacopeias to control and avoid these harmful effects using sensitive and accurate analytical methods. Headspace gas chromatography HS-GC is considered the optimal choice among the different analytical methods due to the volatile nature of the ORS, moreover, the selection of an appropriate sample matrix is a crucial step for this method. Deep eutectic solvents (DESs) have received a great deal of attention in many industries, due to their promising advantages and properties. In this work, different DESs were synthesized using microwave-assisted heating (except for ChCl: Urea 1:2) and investigated for their potential as a sample matrix for ORSs determination using HS-GC technique by investigating the resulting peak areas. Upon investigation, polar ORSs showed greater recovery dependence on the composition of the used DES, while non-polar ORSs did not show a significant change in response to the type of DES used. Consequently, among the different selected DESs, choline chloride: citric acid: glucose (1:1:1) with 15% water content showed the best results and highest ORSs recovery using HS-GC. Injection and heating time were optimized using the selected DES to an injection time of 0.05 minutes and a heating time of 15 minutes. A calibration curve was built for each ORS using the optimized conditions of HS-GC and the DESs as a sample matrix for common pharmaceuticals. The developed method was shown to be able to detect class 2 and 3 residual solvents at limits way lower than the acceptable limits by pharmacopeias. However, for class 1 residual solvents, lower limits of determination are needed, which can’t be achieved using HS-GC only. In such cases, it should be noted that this limitation is not attributed to the use of DESs as sample matrix, the use of SPME or trap HS-GC is necessary. More investigation into their possible applications and effect of water addition as well as possible mixtures is needed to utilize their full potential as an effective green analytical method. |
