Measurement and decomposition kinetics of residual hydrogen peroxide in the presence of commonly used excipients and preservatives (original) (raw)
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Evaluation of Hydroperoxides in Common Pharmaceutical Excipients
Journal of Pharmaceutical Sciences, 2007
While the physical properties of pharmaceutical excipients have been well characterized, impurities that may influence the chemical stability of formulated drug product have not been well studied. In this work, the hydroperoxide (HPO) impurity levels of common pharmaceutical excipients are measured and presented for both soluble and insoluble excipients. Povidone, polysorbate 80 (PS80), polyethylene glycol (PEG) 400, and hydroxypropyl cellulose (HPC) were found to contain substantial concentrations of HPOs with significant lot-to-lot and manufacturer-to-manufacturer variation. Much lower HPO levels were found in the common fillers, like microcrystalline cellulose and lactose, and in high molecular weight PEG, medium chain glyceride (MCG), and poloxamer. The findings are discussed within the context of HPO-mediated oxidation and formulating drug substance sensitive to oxidation. Of the four excipients with substantial HPO levels, povidone, PEG 400, and HPC contain a mixture of hydrogen peroxide and organic HPOs while PS80 contains predominantly organic HPOs. The implications of these findings are discussed with respect to the known manufacturing processes and chemistry of HPO reactivity and degradation kinetics. Defining critical HPO limits for excipients should be driven by the chemistry of a specific drug substance or product and can only be defined within this context.
Optimal methods for quenching H2O2 residuals prior to UFC testing
Water Research, 2003
In this paper, the quenching of hydrogen peroxide by catalase, sodium hypochlorite, sodium thiosulfate and sodium sulfite, prior to UFC testing, was investigated. Sodium hypochlorite, sodium thiosulfate and sodium sulfite were found to be unsuitable for quenching H 2 O 2 residuals because the procedures are time-consuming and complicated in that they require potentially multiple measurements of the peroxide and chlorine residuals. In contrast, quenching of peroxide with catalase is a simple procedure. Catalase doses of less than 0.2 mg/L were found to have no impact on DBP (TTHM, HAA and aldehyde) formation in the UFC test, and the time that was needed to quench 100 mg/L peroxide (room temperature, pH 8.3) was less than 10 min. In addition, peroxide was found to react with DPD reagents that are used to measure chlorine residuals, a phenomenon that may lead to falsely high chlorine residuals in the UFC test. r
Evaluation of a sensitive GC–MS method to detect polysorbate 80 in vaccine preparation
Journal of Pharmaceutical and Biomedical Analysis, 2020
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2017
Some vaccine process manufacturing techniques require the use of acetate (Ac) and phosphate (Pi) containing buffers to complete biochemical reactions prior to downstream product purification. These two anions must be removed from the final bulk product, which necessitates the need for an assay to monitor Ac and Pi reduction throughout. Due to the separation speed, low volume consumption, and resolving power, a capillary electrophoresis (CE) method has been chosen to separate and quantitate the levels of these anions in final product and in-process intermediate samples. Furthermore, this optimized CE method has been successfully qualified and is routinely used to support vaccine process development.
Current Issues in Pharmacy and Medical Sciences
In this study, the stability of 10% hydrogen peroxide aqueous and non-aqueous solutions with the addition of 6% (w/w) of urea was evaluated. The solutions were stored at 20°C, 30°C and 40°C, and the decomposition of hydrogen peroxide proceeded according to first-order kinetics. With the addition of the urea in the solutions, the decomposition rate constant increased and the activation energy decreased. The temperature of storage also affected the decomposition of substance, however, 10% hydrogen peroxide solutions prepared in PEG-300, and stabilized with the addition of 6% (w/w) of urea had the best constancy.
Analytica Chimica Acta, 2002
The development of a highly sensitive method for the determination of nanomolar concentrations of hydrogen peroxide in the liquid phase is described. This paper demonstrates for the first time a flow injection analysis (FIA) system with immobilized enzyme reactor combined with a total internal reflective cell (a liquid waveguide capillary cell (LWCC)) and spectrophotometric detection, for the development of an improved procedure for the determination of hydrogen peroxide. Moreover, the newly synthesized 4-aminopyrazolone derivative, 4-amino-5-(p-aminophenyl)-1-methyl-2-phenyl-pyrazol-3-one (DAP), is used as a color coupler in its oxidative condensation with the sodium salt of N-ethyl-N-sulphopropylaniline sodium salt (ALPS) which acts as a hydrogen donor. Immobilization of peroxidase is achieved by coupling the periodate-treated enzyme to aminopropyl controlled-pore glass (CPG) beads. The determination of hydrogen peroxide is carried out in a 0.1 M phosphate buffer and the product is monitored at 590 nm with a charge-coupled device (CCD) detector equipped with fiber optics in a fully computerized system. The interference of different species, mainly ionic, was investigated.
Flow injection analysis of hydrogen peroxide in disinfectants
1999
A flow injection analysis (FIA) method for the automated determination of hydrogen peroxide in the presence of even stronger oxidants is presented based on the immediate formation of a colored adduct between hydrogen peroxide and a dinuclear iron(III) complex. A reagent stream with the complex and a carrier stream into which the sample is injected are combined in a low dead volume mixing tee. A reaction coil provides for a reaction time of 7 s, after which detection is performed using UV/ vis spectroscopy at 575 nm. Major advantages of the method are the simple experimental setup and the high selectivity even towards stronger oxidants. Real samples have been investigated and the method has been validated using independent techniques including microplate spectrophotometry and HPLC.
Safe use of Hydrogen Peroxide in the Organic Lab
Department of Chemistry, University of Nebraska-Lincoln
Outline Leading references Toxicity Physical properties Chemical properties Stability and incompatibilities Confinement/pressure References to accidents involving H 2 O 2 Leading references Applications of Hydrogen Peroxide and Derivatives offers a very useful introduction, including discussions of: methods for preparation; properties; use as an oxidant in the presence of catalysts; synthetic application; and, environmental applications. 1 The web sites of several suppliers and a paper industry trade group offer information on: physical properties, safety, guidelines for handling/storage/usage, and regulatory requirements. 2 Information on aq. H 2 O 2 solutions is available in the American Chemical Society Reagent Chemicals series. 3 Safety data sheets for commercially available solutions are available from all major vendors; 2 a link to a safety data sheet portal is provided. 4 A review describing industrial synthesis of H 2 O 2 is available. 5 Toxicity Exposure to odorless (no odor threshold is known) hydrogen peroxide vapors has resulted in injuries to several dozen employee. 6 H 2 O 2 (vapor, mist , or aerosol) is considered to hold immediate danger to life and health (IDLH) at 75 ppm; 7 the threshold limit value (TLV) for timeweighted exposure is 1.0 ppm. 8 Dermal exposure to 30% H 2 O 2 can produce skin damage in a few minutes and serious eye damage in only a few seconds. 9,10 Although relatively modest acute toxicities (LD50) are reported for oral and dermal exposure in rodent models (2-4 g/kg and