Document Detail

Analysis of pyrazine 2,5-dipropionic acid in 5-aminolevulinic acid-loaded urological and topical delivery vehicles: methodology and assay validation.
MedLine Citation:
PMID:  15620538     Owner:  NLM     Status:  MEDLINE    
Photodynamic therapy (PDT) using 5-aminolevulinic acid (ALA) is a novel treatment method with much potential benefit for cancer detection and eradication. Formulation into drug delivery systems, such as aqueous solutions and emulsion based creams is complicated by its rapid dimerisation to pyrazine 2,5-dipropionic acid (PY); a compound with scant documentation in terms of toxicity and effect during PDT. This degradation is especially noticeable, where pH is adjusted upwards to avoid local irritation. A good case in point is bladder instillation of ALA for treatment and diagnosis of urothelial neoplasia. This work describes a rapid and validated HPLC method designed to assess the formation of PY in ALA-loaded vehicles. PY eluted as a single peak (Rt=5.0 min) with good intra- and inter-day reproducibility and limits of detection and quantification found to be 0.01 and 0.04 microg ml(-1), respectively. Sample stability for upto 16 h was demonstrated, allowing autoinjection cycles to be performed. PY formation was detected in typical buffers used for bladder instillation after 6 h of storage, emphasising the need to use these preparations immediately upon manufacture if intended for photodynamic purposes. Moreover, upto 2.35% (w/w) PY was detected in artificial urine after 6 h storage at ambient temperature indicating that formation in vivo is likely to occur once bladder instillations are in situ and exposed to endogenous urine. As a result, ALA instillation times should be kept to the minimum needed for safe and successful treatment or diagnosis. PY extraction from semi-solid devices approached 100% efficiency demonstrating that the reported assay is suitable for evaluating stability of novel dosage forms intended for ALA delivery.
Paul A McCarron; Ryan F Donnelly; A David Woolfson; Gavin P Andrews
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Publication Detail:
Type:  Comparative Study; Journal Article; Validation Studies    
Journal Detail:
Title:  Journal of pharmaceutical and biomedical analysis     Volume:  36     ISSN:  0731-7085     ISO Abbreviation:  J Pharm Biomed Anal     Publication Date:  2005 Jan 
Date Detail:
Created Date:  2004-12-28     Completed Date:  2005-06-03     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  8309336     Medline TA:  J Pharm Biomed Anal     Country:  England    
Other Details:
Languages:  eng     Pagination:  1099-105     Citation Subset:  IM    
School of Pharmacy, Queens University of Belfast, Medical Biology Centre, 97 Lisburn Road, Belfast, N. Ireland BT9 7BL, UK.
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MeSH Terms
Administration, Topical
Aminolevulinic Acid / administration & dosage,  analysis*,  chemistry
Drug Delivery Systems / methods*
Propionic Acids / administration & dosage,  analysis*,  chemistry
Pyrazines / administration & dosage,  analysis*,  chemistry
Urinary Bladder* / drug effects
Reg. No./Substance:
0/Propionic Acids; 0/Pyrazines; 106-60-5/Aminolevulinic Acid

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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