Development and validation of reversed phase chromatography method for the determination of process and degradation impurities in Duloxetine Hydrochloride delayed release capsules

Abstract

Duloxetine Hydrochloride is a delayed-release serotonin and norepinephrine reuptake inhibitor (SNRI) administered orally, utilized for the treatment of depression and anxiety by enhancing the levels of mood-regulating neurotransmitters, serotonin and norepinephrine, in the brain. Drug classified as BCS Class-II, having low solubility and high permeability. The dissociation constant (pKa) of Duloxetine Hydrochloride was determined to be 9.7, and the molecule is strong basic in nature.  However, Gradient methods with longer runtimes were published to determine the selective impurities of Duloxetine. The study reported here is an isocratic method with the shortest possible run time with selective impurities (process and degradation impurities) of Duloxetine.   Forced degradation studies were performed on Duloxetine Hydrochloride Capsules using Acid, Base, Oxidative (Peroxide), Humidity, Thermal and Photolytic stress conditions. The identified unknown degradants were well resolved from the known impurities and the mass balance found close to 100% in all the stress conditions applied. The chromatographic technique was optimized utilizing stress samples from stress degradation investigations. The analytical method was validated in accordance with ICH requirements.  The obtained validation results demonstrate the developed analytical method can be employed in routine chemical analysis for the determination of known impurities i.e. Duloxetine alcohol impurity (Duloxetine EP impurity B), Duloxetine Alpha Naphthol impurity (Duloxetine EP impurity D) and Duloxetine β-Naphthol-1-yl-isomer (Duloxetine EP impurity E) and unknown impurities (any unspecified impurities).