1. INTRODUCTION

For pharmacopeial purposes, residual solvents in pharmaceuticals are defined as organic volatile chemicals that are used or produced in the manufacturing of drug substances, excipients, or dietary ingredients, or in the preparation of drug products or dietary supplement products. Appropriate selection of the solvent for the synthesis of a drug substance or an excipient may enhance the yield or determine characteristics such as crystal form, purity, and solubility. Therefore, the solvent may sometimes be a critical element in the synthetic process and may not be completely removed by the manufacturing process. Because residual solvents do not provide therapeutic benefit, they should be removed, to the extent possible, to meet safety-based limits, ingredient and product specifications, good manufacturing practices, or other quality-based requirements.