Estimation and Controlled Analytical Strategy of Benzene as Trace Toxic Carcinogen in Solvents and Pharmaceuticals

In pharmaceuticals the Residual solvents are volatile classified as the organic solvents which are utilised in the production of drug (substances and also in finished drug products). Solvents are a vital part of the generation of active pharmaceutical ingredients (APIs), and drug products, the correct choice amongst many, could lead to a higher reaction rate and other critical characteristics of crystalline structure, purity, and solubility. Solvents and associated impurities are part of the core manufacturing process, hence, they may not be completely removed in the manufacturing processing stage, and may be left in the finished final product. Consequently, due to this, the residual solvents are also an issue of critical concern in pharmaceutical development and production. Residual solvent tests are not usually stated within individual monographs since the solvents type taken may vary across manufacturers’ selection process. Not only may such solvents be dangerous to the environment they can also be harmful to patients in case they are found in excessive amounts. As such, there exist acceptable levels of residual solvents in the ICH guideline Q3C (R9). This guideline involves the classification of residual solvents in three groups, depending on their possible risk to human health, which considers both the toxicity data and the environmental issues. Class 1 solvents should not be used in drug production, as they are known to be human carcinogens, very toxic, and environmentally dangerous and some also contribute to ozone depletion, which are- benzene (2 ppm), carbon tetrachloride (4 ppm), 1, 2-dichloroethane (5 ppm), 1, 1 -dichloroethane (8 ppm), and 1, 1 - trichloroethane (1500 ppm). However, even when using other common solvents they could still have traces of these solvents as impurities. As an example, benzene can be present in ethanol, methanol, acetone and isopropyl alcohol and 1,1-dichloroethane and 1,1-trichloroethane can be present in dichloromethane. Hence, one must be very keen to observe and put strict measures on the content of such harmful solvents in the solvents utilized in the pharmaceutical manufacturing process.