Search

In the production of doxofylline, the common occurrence of toxic p-toluene sulfonate generation prompted the development and validation of a method using HPLC with ultraviolet detection (HPLC-UV). This method is designed for detecting four potential genotoxic impurities (PGIs) present in both doxofylline drug substance and tablets, with a focus on the UV-absorbing group p-toluene sulfonate. The four impurities were methyl 4-methylbenzenesulfonate (PGI-1), ethyl 4-methylbenzenesulfonate (PGI-2), 2-hydroxyethyl 4-methylbenzenesulfonate (PGI-3), and 2-(4-methylphenyl)sulfonyloxyethyl 4-methylbenzenesulfonate (PGI-4). In this method, chromatographic separation was achieved using a Waters Symmetry C 18 column (250 mm × 4.6 mm, 5 μm). The mobile phases consisted of 20% acetonitrile as mobile phase A and pure acetonitrile as mobile phase B, operating in gradient elution mode at a flow rate of 1.0 mL/min. According to the guidelines of the International Conference on Harmonization, it was determined that this method could quantify four PGIs at 0.0225 μg/mL in samples containing 60 mg/mL. The validated approach demonstrated excellent linearity (R 2 > 0.999) across the concentration range of 30%-200% (relative to 0.075 μg/mL doxofylline) for the four PGIs. The accuracy of this method for the four PGIs ranged from 94.8% to 100.4%. The reverse-phase-HPLC-UV analytical method developed in this study is characterized by its speed and precision, making it suitable for the sensitive analysis of benzene sulfonate PGIs in doxofylline drug substances and tablets., (© 2023 John Wiley & Sons Ltd.)

Background: The purpose of this study was to estimate the proportion of Chinese cancer survivors experiencing financial hardship and then examine the relationship between material and behavioral financial hardship., Methods: This study surveyed 964 cancer survivors who were 30 to 64 years old and 644 survivors who were 65 years old or older during 2015-2016 (1608 survivors in all). Material financial hardship was measured by whether they had borrowed money because of cancer, its treatment, or the lasting effects of treatment, and behavioral financial hardship was measured by whether they had forgone some cancer-related medical care because of cost. Multivariable logistic regression models were used to examine factors associated with material financial hardship by age group., Results: Approximately 44% of the cancer survivors who were 65 years old or older borrowed money or went into debt because of cancer, and 54% of younger patients (P < .01) reported cancer-related debts. Among these survivors with cancer care debt, survivors aged 65 years old or older had a lower proportion of borrowing more than 50,000 Chinese yuan (CNY; approximately US $7700) than survivors aged 30 to 64 years (14% vs 20%). In both age groups, approximately 10% of cancer survivors reported that they had experienced behavioral financial hardship. After adjustments for covariates, cancer survivors who reported material financial problems were more likely to report behavioral financial hardship (odds ratio [OR] for those aged 30-64 years, 3.72; 95% confidence interval [CI], 2.13-6.50; OR for those aged 65 years or older, 5.48; 95% CI, 2.69-11.15)., Conclusions: Older cancer survivors in China experience significant material financial hardship, but it is not as noticeable as younger patients' hardship. The results highlight the importance of identifying cancer survivors who are more likely to experience financial hardship and improving the affordability of cancer care in China., (© 2020 American Cancer Society.)

A series of chiral pyrrolidine-sulfamides were prepared and examined as the catalysts for conjugate addition of ketones to nitroalkenes. Benzoic acid was identified as the most efficient additives for the transformation. Excellent enantioselectivities, diastereoselectivities, and yields were achieved for the reaction of cyclohexanone with β-aryl nitroethylenes under solvent free conditions. β-Isopropyl nitroethylene is also applicable and the product could be obtained with excellent enantioselectivity after extended reaction time. A comparison of the catalytic behaviors of pyrrolidine-sulfamide organocatalysts with different side chains demonstrates that the enantioselectivity is mainly controlled by the chiral pyrrolidine unit and the additional chiral center at the side chain exerts neglectable effects. The H-bonding interaction between the sulfamide and the nitro group is proposed to be crucial for the activation of the nitroalkene and the constitution of well-organized transition state., (Copyright © 2012 Wiley Periodicals, Inc.)

Background: Several aromatase inhibitor studies have reported variations in the inhibitory potency of these agents that could lead to differences in clinical outcomes. In the current study, the authors formally evaluated the activity of anastrozole and exemestane in postmenopausal women with hormone-responsive, advanced breast cancer., Methods: Postmenopausal women who had measurable disease according to Response Evaluation Criteria in Solid Tumors and had not received previous endocrine therapy for advanced breast cancer were randomized to receive either oral exemestane 25 mg daily or oral anastrozole 1 mg daily until they had disease progression. The primary endpoint was the objective response rate (ORR), and secondary endpoints included the clinical benefit rate (CBR), time to progression (TTP), overall survival, and safety. Crossover to the other aromatase inhibitor was permitted at the time of disease progression; ORR, CBR, and TTP after second-line treatment also were explored., Results: In total, 103 patients were enrolled. The median patient age was 71.6 years, 52.4% of patients had visceral disease, and 75.8% of patients had ≥ 2 disease sites. Half of the patients had received previous tamoxifen, and 60% had received previous chemotherapy. The efficacy observed in the exemestane and anastrozole groups was an ORR of 36.2% and 46%, respectively; a CBR of 59.6% and 68%, respectively, and a TTP of 6.1 months and 12.1 months, respectively. At progression, 28 patients crossed over to the other aromatase inhibitor, including 16 patients who switched to exemestane (CBR, 43.7%; TTP, 4.4 months) and 12 patients who switched to anastrozole (CBR, 8.3%; TTP, 2 months). Both drugs were generally well tolerated, and no study drug-related serious adverse events were reported., Conclusions: In this phase 2 randomized trial, no significant differences in clinical activity were observed in favor of exemestane to justify a superiority phase 3 trial design in the first-line setting., (Copyright © 2011 American Cancer Society.)