ABSTRACT
@#An HPLC pre-column derivatization detection method was established to detect and analyze the formaldehyde and acetaldehyde in polysorbate 80 and polysorbate 20 from different manufacturers.The effects of aldehyde and acetaldehyde on the aggregation of adalimumab under different conditions were monitored.Based on the control of genotoxic impurities and the influence on the stability of monoclonal antibody preparations, the control limits of the two chemicals were preliminarily obtained.2, 4-dinitrophenylhydrazine (2, 4-DNPH) was applied as the derivatization reagent in HPLC pre-column derivatization; acetonitrile and water were used as mobile phase to perform a gradient elution on a C8 (4.6 mm × 150 mm, 5 μm) chromatographic column.The detection wavelength was 360 nm, and the external standard method was used for quantification.Verification results showed that the method was suitable for the quantitative analysis of trace formaldehyde and acetaldehyde in polysorbate 80 and polysorbate 20 . The detection and analysis of formaldehyde or acetaldehyde in different batches of polysorbate 80 and polysorbate 20 from different manufacturers showed that the content of formaldehyde and acetaldehyde were quite different. The content of formaldehyde and acetaldehyde in polysorbate 80 were significantly higher than those of polysorbate 20. After monitoring the changes of adalimumab aggregates treated by formaldehyde and acetaldehyde by size exclusion chromatography (SEC), it was found that the effect of formaldehyde on adalimumab aggregation was significantly higher than that of acetaldehyde.According to the requirements of ICH M7 (International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use, M7: Assessment and Control of DNA Reactive (Mutagenic) Impurities in Pharmaceuticals to Limit Potential Carcinogenic Risk), the impurity limits of formaldehyde and acetaldehyde in polysorbate 80 and polysorbate 20 for monoclonal antibody preparations were calculated from the perspective of risk assessment.Combined with the influence on the aggregation stability of monoclonal antibodies, the preliminary limis for acetaldehyde and acetaldehyde were recommended to be ≤ 7 μg/g and ≤ 765 μg/g, respectively.
ABSTRACT
Pressure-limit ventilators are used because it is believed that they decrease the incidence of pulmonary gas leaks and chronic lung disease. The disadvantage of pressurelimit ventilators is that there is no automatic compensation for changes in compliance and resistance of the lung and the chest wall. Consequently, if lung compliance decreases, tidal volume will decrease and blood gases will worsen. The aim of this study is to find the adequacy for the oxygenation and ventilation of volume-limit ventilator with pressure-limit control accessary in pediatric patient with congenital heart disease. The pressure-limit control accessary for anesthetic ventilator(AV-E, North America Drager, Bedford, USA) in 36 pediatric patients undertaken open heart surgery and thoracotomy, retrospectively, were employed. The patients were divided into 3 groups according to their body weights. The respiratory rate of group I ( or = 5, or = 10, < 20 kg, n=8) was 15/min. The patients were divided into another 2 groups, A(n=30) or B(n=6), with the supine or lateral, respectively according to the operation position. The results showed all the values of arterial blood gases almost within normal limits, except one patient in each group. We concluded that anesthetic Drager infant ventilator with pressure-limit control accessary was useful during controlled ventilation, and this is suitable for the prolonged operation in pediatric patients with the supine or lateral position.