Imatinib mesylate (IM) is an anti-neoplasic drug used for the treatment of cancer. Recent new guidelines specify daily doses and concentration limits for genotoxic impurities (GTIs) in pharmaceutical final products. Therefore, in this work an analytical method using UHPLC-MS/MS was developed, validated and applied to characterize IM tablets for two GTIs: N-(2-methyl-5-aminophenyl)-4-(3-pyridyl)-2-pyrimidine amine (Imp. 1), and N-[4-methyl-3-(4-methyl-3-yl-pyrimidin-2-ylamino)-phenyl]-4- chloromethyl benzamide (Imp. 2), simultaneously. Additionally, dissolution data of IM tablets were compared using a methodology recommended by the US Food and Drug Administration. The UHPLC method utilized an Acquity BEH C (150 × 2.1 mm, 1.7 μm) maintained at 40°C. The mobile phase consisted of ammonium formate 0.063% (phase A) and acetonitrile plus 0.05% formic acid (phase B) in gradient elution. A sensitive method for determination of previously mentioned GTIs in IM tablets was successfully developed and applied. Overall, the formulations analyzed in this work showed low levels of Imp. 1 and Imp. 2. However, the sample named D1 showed very high levels of Imp. 1 and failed to meet the requirements established by the US Food and Drug Administration for dissolution data. Periodic verification of GTIs in pharmaceutical formulations is important to minimize safety risks, so analytical methods to determine it need be available and implemented in routine analysis.
Polymyxins are a group of antibacterial substances and have remained the drugs of choice for treatment of resistant Gram-negative bacilli. Polymyxin B is administered by intravenous infusion and requires the reconstitution of lyophilized powder with 0.9% saline or 5% glucose solutions. To date, there is little information about polymyxin stability in different infusions solutions, especially at 40 ºC, a temperature that is recommended to study drug stability as it accelerates degradation reactions. Therefore, in this work an analytical method using LC-MS/MS was developed, validated and applied to determine the stability of polymyxin B diluted in 0.9% saline or 5% glucose solutions at 25 ºC and 40 ºC. The stability of polymyxin B solutions was evaluated during 72 hours. Polymyxin B1 and B2 were stable for 24 hours in saline (0.9%) and glucose solution (5%), however a significant degradation of polymyxin B1 and B2 was observed after 48 hours and 72 hours of assay. The reduction of polymyxin content was evidenced in both saline and glucose media, at room temperature as well as at 40 °C. No significant differences in pH of polymyxin solutions (glucose or saline) were evidenced during stability assay.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.