Incorporating solid-phase extraction into compendial procedures for the determination of dexamethasone and impurities in low-dose drug products

Abstract

A low-dose drug product is characterized by extremely low concentrations of analytes and a high ratio of excipients to the drug substance; the analysis of these drug products presents a number of analytical challenges for detection and quantitation, which in turn could impact potency, purity, and uniformity of the dosage units. In this work solid-phase extraction (SPE) was used to enrich analytes and minimize the interference of excipients, despite the fact that the application of SPE to pharmaceutical dosage forms is surprisingly uncommon. Specifically, in the development of compendial procedures for two dexamethasone (DEX) low-dose drug products, elixir 0.1 mg/mL and oral solution 0.1 mg/mL, a SPE protocol using Oasis HLB cartridges was developed for sample preconcentration and clean-up. The protocol was rigorously evaluated to ensure high recoveries and repeatability for DEX and its eight impurities (100 ± 2% and RSD ≤ 2.0% for DEX; 100 ± 5% and RSD ≤ 2.0% for impurities). In addition, Strata and Strata X cartridges were identified as an alternative cartridge for the elixir and oral solution, respectively. Furthermore, the extraction efficiency of the SPE protocol was evaluated by comparing the sample preparations with and without SPE using a regular-dose product (DEX Intensol oral solution 1 mg/mL). The SPE-based HPLC method was validated as an effective procedure for the determination of DEX and impurities in DEX elixir and oral solution. The case study demonstrated that incorporation of SPE into USP monographs could significantly strengthen compendial procedures for quality control.