Residual solvents

Lasmiditan Hemisuccinate (LDT) is an innovative medication designed for the treatment of acute migraines, operating by activating 5-HT1F receptors found within the central nervous system. The synthesis of LDT necessitates the use of various solvents. According to regulatory standards, assessing the levels of residual solvents in drug substances is imperative in API (Active Pharmaceutical Ingredients). Present study concentrates on the evaluation and validation of a method for quantifying residual solvents like methanol, acetone, isopropyl alcohol, dichloromethane, methyl ter. butyl ether, n-hexane, ethyl acetate, n-heptane in LDT. Analysis was conducted using a DB-1 capillary column, measuring 60 meters in length with an internal diameter of 0.32 mm and a film thickness of 5 µ. The oven temperature was set to 65°C for 12 minutes, followed by a ramping rate of 15°C per minute to reach 85°C, where it was held for 5 minutes. Subsequently, a second ramping phase increased the temperature at a rate of 10°C per minute until it reached a final temperature of 220°C, which was maintained for 5 minutes. The injector temperature was maintained at 200°C and nitrogen was utilized as the carrier gas with 1-methyl-2-pyrrolidinone (NMP) diluent serving as the sample solvent. A suitable sensitive and robust HSGC-FID method is developed for quantitation of residual solvents with flame ionization (FID) detector. The evaluated method can applied to analyse of solvents present in a various range of APIs, intermediates.

Solvents are widely used during the manufacturing, purification and processing of pharmaceutical substances. The residues of these solvents must be removed to the extent possible, as they do not have any therapeutic effect but can cause undesirable effects in the consumers. These solvent residues concentration should not exceed the limits prescribed in the ICH guidelines.  This present review work is emphasized on various techniques (Loss on drying, karl fischer titration, Thermogravimetric analysis, Near- IR spectroscopy, Thermal desorption GC-MS, Gas chromatography, Nuclear magnetic resonance spectroscopy) that are being used to remove the residual solvents with their merits and demerits.