Assessment by HPLC of the degradation behavior of acitretin under hydrolytic, oxidative, photolytic and thermal stress conditions

Abstract

Acitretin is a photosensitive oral retinoid with very limited data available on its degradation. The official HPLC method for acitretin determination was insufficient to resolve the degradation products generated during stability studies. Therefore, an isocratic RP-HPLC–UV method was developed for the determination of acitretin in the presence of its related impurities and degradation products. Efficient chromatographic separation was achieved on a Thermo beta-basic column C18 (100 mm×4.6 mm, 5 μm) with mobile phase containing 0.3% (v/v) glacial acetic acid with acetonitrile (ACN) and isopropyl alcohol (IPA) in an isocratic ratio of 70:30 at a flow rate of 1.0 mL/min with the eluent monitored at 360 nm. The method was validated for specificity, linearity, precision, accuracy and robustness. The calibration plot was linear over the concentration range of 50–150 μg/mL with a correlation coefficient (r2) of 0.999. The proposed method was used to investigate the degradation kinetics of acitretin under the different degradative conditions. The degradation rate constant (K), half-life (t1/2), and t90 were calculated. Degradation of acitretin followed pseudo-first-order kinetics. The drug was found to be less stable under acidic and photolytic degradation conditions: the photolytic degradation constants for acitretin in sunlight and UV light were 0.002698% and 0.0008402% min−1, respectively. The LOD for acitretin and the known impurities were at a level below 0.02%. The method shows consistent recoveries for ACTR (99.8%–101.2%) and also for its known impurities (97.2–101.3%). The method was found to be accurate, precise, linear, specific, sensitive, rugged, robust, and useful for characterizing the stability of this chemical.

Comprehensive Review on the Degradation Chemistry and Toxicity Studies of Functional Materials

“…Identification and quantitation are also possible with RP-HPLC. The procedure can also be used to assess the stability of acitretin . An isocratic reversed-phase-high-performance liquid chromatography (RP-HPLC) with ultraviolet–visible spectroscopy (UV–vis) method was developed to calculate acitretin in the presence of its associated impurities and degradation products.…”

“…The procedure can also be used to assess the stability of acitretin. 133 An isocratic reversed-phase-high-performance liquid chromatography (RP-HPLC) with ultraviolet−visible spectroscopy (UV−vis) method was developed to calculate acitretin in the presence of its associated impurities and degradation products. To calculate known and unknown impurities and degradation materials, the procedure should be specific.…”

A Unique Preparation and Delivery Method for Acitretin for Neonatal Harlequin Ichthyosis

“…6 Because BUD may differ from case to case depending on the storage conditions, we were cautious and used the lowest BUD for acitretin to ensure maximum efficacy of the medication for our patient. In light of the studies that have focused on the occupational exposure hazards of chemotherapeutic drugs, it is now well recognized that several drugs have a toxicity profile, like the teratogenicity of acitretin, 9 which is of concern. There is also evidence that health care workers are exposed to chemotherapeutic agents and other hazardous drugs at delivery sites, while pharmacists are exposed during the preparation of these drugs.…”

“…It retains its suspending properties, even when diluted with up to 50% water or flavoring agents, making it ideal for pediatric suspensions and nasogastric preparations. Further, as acitretin degrades on exposure to photolytic stress with an increase in degradation products and impurities, 9 the preparation of the solution and its long-term storage must be done to minimize exposure to photolytic stress, which is achieved by storing the solution in amber-colored glass bottles.…”

Fungal Secondary Metabolites: Fusarium spp. and Microdochium spp.

“…Moreover, it is unstable at room temperature and sensitive to light exposure . During the analytical analysis reducing of the peak areas (Porwal & Upmanyu, 2014) and detecting of new peaks mutant. There is no resembling naphthoquinone natural product that can be found in Reaxys and PubChem databases for this sum formula .…”