28325-47-5Relevant articles and documents
A liquid chromatographic study of stability of the minor determinants of penicillin allergy: A stable minor determinant mixture skin test preparation
Ressler,Neag,Mendelson
, p. 448 - 454 (1985)
Various skin test reagents supplying minor determinants for detecting penicillin hypersensitivity have been examined by high-performance liquid chromatography (HPLC) for composition and stability. HPLC systems capable of separating and determining the four diastereoisomers of benzyl-D-penicilloic acid and the two benzyl-D-penilloic acids were developed for this purpose. The 'simple skin test reagent', consisting of an aged partial alkaline hydrolysate of penicillin, is possibly an adequate source of (5R,6R)-benzyl-D-penicilloate whereas the 'simple skin test reagent,' consisting of aged aqueous solution of penicillin, is a questionable source of this compound. A modified Levine, Voss, Redmond, and Zolov minor determinant mixture (MDM) reagent and the components (5R,6R)-benzyl-D-penicilloate and (5R)-benzyl-D-penilloate have been found to be highly labile in aqueous solution, giving rise to a mixture of diastereoisomers. The tendency to epimerize at C-5 was a prominent feature of (5R,6S)- and (5S,6R)- as well as (5R,6R)-benzyl-D-penicilloic acids. The MDM reagent has been prepared in single-dose ampules as a dried, lyophilized powder that can be stored without change and used as needed. Lyophilized MDM has served as a satisfactory substitute for freshly prepared MDM in several individuals with MDM-positive history and, in a recent clinical study, evaluating the question of penicillin skin test sensitization. This convenient, stable, single-dose form of the MDM reagent should facilitate skin testing for penicillin sensitivity.
Investigation of a Proposed Penicillin G Acidic Degradation Scheme using High-pressure Liquid Chromatography and Optimization Techniques and Mechanistic Considerations
Kessler, David P.,Cushman, Mark,Ghebre-Sellassie, Isaac,Knevel, Adelbert M.,Hem, Stanley L.
, p. 1699 - 1704 (2007/10/02)
Optimization techniques were used to fit a recently proposed degradation scheme to recently published n.m.r. data for the time course of penicillin G and four degradation products at pH 2.5 and 37 deg C.Several conclusions arising from the n.m.r. analysis which were originally associated with the degradation scheme were not compatible with the optimized rate constants.It was necessary to change substantially the proportion of penicillin G degrading through benzylpenicillenic acid, benzylpenillic acid, and benzylpenicilloic acid in order for the degradation scheme to fit the n.m.r. data.Benzylpenillic acid replaced benzylpenicillenic acid as the major product.The rate constants best describing the n.m.r. data showed benzylpenicillenic acid proceeding almost exclusively through benzylpenamaldic acid.Such optimization implied that the scheme could be simplified to three parallel reaction pathways, the dominant reaction occurring through benzylpenillic acid.However, mechanistic considerations indicate that the direct conversion of penicillin G into benzylpenillic acid is not possible and that a likely intermediate is benzylpenicilloic acid.The degradation of benzylpenicilloic acid at pH 2.5 was consequently monitored by ionpair reversed-phase high-pressure liquid chromatography and rapid formation of benzylpenillic acid was detected.This observation is inconsistent with the recently proposed degradation scheme, even though the scheme can be made to fit the n.m.r. kinetic data.
