GC-FID-HS method development and validation for quantitative estimation of ethanol as residual in tablets drug product from the class of benzodiazepine

The purpose of this study is to explain why and how to give an understandable concept for the implementation of a trustworthy GC-FID-HS method which will be used for the determination of residual ethanol in solid dosage form (tablets). The tablets drug product belongs to a class of medications benzodiazepines which are used to treat panic attacks with or without agoraphobia, anxiety states of different severity, including those associated with depression, agitation, restlessness and tension accompanied with or without psychosomatic symptoms as well as anxiety which accompanies depressive disorder. As a central nervous system depressant, ethanol is one of the most commonly consumed psychoactive drugs. Ethanol serves many purposes in medicines, as a solvent, preservative, or cutaneous penetration enhancer. Although, ethanol can impair cognitive and psychomotor functions so exposure to ethanol when used as an excipient in medicines is usually limited. Exposure is affected by the dose volume and weight of the patient. This solvent was evaluated for its possible risk to human health. Therefore, the analysis of ethanol is a necessary tool for the standard management of prescribed drugs (Umamheswari et al., 2021). The concentration of residual ethanol should not exceed the limit prescribed in the ICH guidelines for Class 3 residual solvents (ICH Q3C (R6), 2018; ICH Q3C (R8), 2020). Ethanol anhydrous was used for the preparation of binder solution during the manufacturing process of tablets but it cannot be completely removed by common manufacturing techniques so it was necessary to validate sensitive and accurate method for estimation of ethanol. Some methods according to several literary data, have been established for the analysis of ethanol, using a mix of several diluents as dissolving solutions (Alahmad et al., 2013) or solid phase microextraction headspace method (Hanwar et al., 2022). However, it is taking too much time and money. This GCFID-HS method is considered to be a less expensive and fast method for the estimation of ethanol in tablets and it has been widely employed in the analysis. The method was validated according to ICH guidelines Q2 (R2), following various parameters such as specificity, linearity, precision, accuracy, robustness, the limit of quantification (LOQ) and the limit of detection (LOD). The objective of the development and validation of an analytical procedure is to show that it is suitable for the intended purpose (ICH, 2022).