Screening methods for impurities in multi-sourced fluoxetine hydrochloride drug substances and formulations

Abstract

Gradient high-performance liquid chromatography (HPLC) and gas chromatography were applied as screening methods for determination of impurities in fluoxetine hydrochloride drug substances and formulated products from multiple sources. Nuclear magnetic resonance spectroscopy was also used for identification of excipients and some residual solvents. Thirty potential impurities and excipients were investigated. Several impurities were observed in generic products using gradient HPLC that were not detected with isocratic pharmacopeial methods for fluoxetine hydrochloride. Analysis of drug substance samples and capsule formulations from many different suppliers showed a wide variation in quality which, in many cases, would go undetected using isocratic methods. The quality of the innovator's product and some generic samples was high, but many generic samples contained high levels of impurities. A new impurity, N-benzyl fluoxetine, was observed in some generic samples at levels as high as 0.9 %. The gradient HPLC method was also used for stability studies and established that generic capsules formulated with lactose were less stable under accelerated conditions than those formulated without lactose.

Determination of organic impurities in pharmaceutical preparations

“…Separation is commonly performed at room temperature; less frequently, the column is thermostatted at 40-45°ë [47][48][49]. Gradient elution is used for the separation of impurities with different polarities [50][51][52][53][54][55]. This approach, on the one hand, improves the separation of the mixture and decreases the time of analysis and, on the other hand, complicates the analysis, impairs the reproducibility, and narrows the range of suitable detectors (only detectors unresponsive to a change in the composition of the mobile phase in the course of chromatography are suitable for gradient elution).…”

“…Normal-phase HPLC is very rarely used for the determination of organic impurities in pharmaceutical preparations [46][47][48][49][50][51][52][53][54][55][56][57][58][59][60], because their components and impurities are commonly polar compounds. In the majority of cases, unmodified silica gel [56,[58][59][60] and silica gel with modifying amino groups [57] are used as polar sorbents for the determination of impurities by normal-phase HPLC.…”

Food‐Related Carbohydrate Ligands for Galectins

“…With a host of detection methods currently available, lactulosamine formation has been confirmed in UHT milk (74,78,83), dried milk (74,78,83,84), infant formulas (83,84), whey (83,85,86), chocolate (83,87), cheese (84), soy milk (87), and drug formulations containing powdered lactose (88,89). These same analytical techniques have been indispensable for tracking lactulose-lysine in blood, urine, and feces to establish metabolic fates of ingested lactulosamine in LA-containing foods.…”

Determination of organic impurities in pharmaceutical preparations

“…Normal-phase HPLC is very rarely used for the determination of organic impurities in pharmaceutical preparations [46][47][48][49][50][51][52][53][54][55][56][57][58][59][60], because their components and impurities are commonly polar compounds. In the majority of cases, unmodified silica gel [56,[58][59][60] and silica gel with modifying amino groups [57] are used as polar sorbents for the determination of impurities by normal-phase HPLC.…”