title: Measurement and decomposition kinetics of residual hydrogen peroxide in the presence of commonly used excipients and preservatives.
abstract: Quantitation of residual hydrogen peroxide (H(2)O(2)) and evaluation of the impact on product stability is necessary as unwanted H(2)O(2) can potentially be introduced during the manufacturing of pharmaceuticals, biologics, and vaccines. A sensitive and convenient microplate-based method with fluorescence detection for H(2)O(2) quantitation was recently reported (Towne et al., 2004, Anal Biochem 334: 290-296). This method was found to be highly robust and reproducible, with a level of detection of 0.015 ppm and a level of quantitation of 0.025 ppm (in water). The relatively small sample requirements and amenability for automation make this assay an attractive tool for detecting residual H(2)O(2) levels. Without additional manipulation, the assay can be conducted on heterogeneous solutions with significant degree of turbidity, such as the presence of suspensions or aluminum-containing adjuvants. The quantitation of H(2)O(2) and its decomposition kinetics was also studied in presence of two common vaccine preservatives (thimerosal and phenol) and eight commonly used excipients (polyols). Over time, there is a distinct, temperature dependent decrease in H(2)O(2) recovered in thimerosal and phenol containing samples versus non-preservative containing controls. Based on the half-life of spiked H(2)O(2), the decay rates in eight polyols tested were found to be: ribose > sucrose > (glycerol, glucose, lactose, mannitol, sorbitol, and xylose).
authors.affiliation: Department of Bioprocess and Bioanalytical Research, Merck Research Laboratories, West Point, Pennsylvania 19486, USA. victoria_towne@merck.com
authors.forename: Victoria
authors.initials: V
authors.lastname: Towne
authors.forename: C Brent
authors.initials: CB
authors.lastname: Oswald
authors.forename: Robin
authors.initials: R
authors.lastname: Mogg
authors.forename: Joseph
authors.initials: J
authors.lastname: Antonello
authors.forename: Mark
authors.initials: M
authors.lastname: Will
authors.forename: Juan
authors.initials: J
authors.lastname: Gimenez
authors.forename: Michael
authors.initials: M
authors.lastname: Washabaugh
authors.forename: Robert
authors.initials: R
authors.lastname: Sitrin
authors.forename: Qinjian
authors.initials: Q
authors.lastname: Zhao
mesh_terms: D004396:Coloring Agents / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004355:Drug Stability; D005079:Excipients / Q000032:analysis*; D006861:Hydrogen Peroxide / Q000032:analysis* / Q000494:pharmacology; D006863:Hydrogen-Ion Concentration; D007700:Kinetics; D010078:Oxazines / Q000494:pharmacology; D010084:Oxidation-Reduction; D019800:Phenol / Q000032:analysis*; D011310:Preservatives, Pharmaceutical / Q000032:analysis*; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D013696:Temperature; D013849:Thimerosal / Q000032:analysis*; D014867:Water / Q000737:chemistry
chemical_list: D004396:Coloring Agents; D005079:Excipients; D010078:Oxazines; D011310:Preservatives, Pharmaceutical; D014867:Water; D013849:Thimerosal; D019800:Phenol; C014180:resorufin; D006861:Hydrogen Peroxide