Analysis of pyrazine 2,5-dipropionic acid in 5-aminolevulinic acid-loaded urological and topical delivery vehicles: methodology and assay validation

P. A. McCarron, R. F. Donnelly, A. D. Woolfson, G. P. Andrews

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

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 (R-1 = 5.0 min) with good intra- and inter-day reproducibility and limits of detection and quantification found to be 0.01 and 0.04 mug 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 It 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. (C) 2004 Elsevier B.V. All rights reserved.
LanguageEnglish
Pages1099-1105
JournalJournal of Pharmaceutical and Biomedical Analysis
Volume36
Issue number5
Publication statusPublished - 28 Oct 2005

Fingerprint

Pyrazines
Aminolevulinic Acid
Intravesical Administration
Acids
Photochemotherapy
Urine
Dosage Forms
Dimerization
Drug Delivery Systems
Emulsions
Documentation
Limit of Detection
Neoplasms
Buffers
Therapeutics
High Pressure Liquid Chromatography
Equipment and Supplies
Temperature

Keywords

  • Pyrazine 2
  • 5-dipropionic acid
  • 5-Aminolevulinic acid
  • Photodynamic therapy
  • Drug delivery
  • Assay validation
  • Degradation

Cite this

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title = "Analysis of pyrazine 2,5-dipropionic acid in 5-aminolevulinic acid-loaded urological and topical delivery vehicles: methodology and assay validation",
abstract = "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 (R-1 = 5.0 min) with good intra- and inter-day reproducibility and limits of detection and quantification found to be 0.01 and 0.04 mug 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 It 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. (C) 2004 Elsevier B.V. All rights reserved.",
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Analysis of pyrazine 2,5-dipropionic acid in 5-aminolevulinic acid-loaded urological and topical delivery vehicles: methodology and assay validation. / McCarron, P. A.; Donnelly, R. F.; Woolfson, A. D.; Andrews, G. P.

In: Journal of Pharmaceutical and Biomedical Analysis, Vol. 36, No. 5, 28.10.2005, p. 1099-1105.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Analysis of pyrazine 2,5-dipropionic acid in 5-aminolevulinic acid-loaded urological and topical delivery vehicles: methodology and assay validation

AU - McCarron, P. A.

AU - Donnelly, R. F.

AU - Woolfson, A. D.

AU - Andrews, G. P.

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PY - 2005/10/28

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N2 - 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 (R-1 = 5.0 min) with good intra- and inter-day reproducibility and limits of detection and quantification found to be 0.01 and 0.04 mug 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 It 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. (C) 2004 Elsevier B.V. All rights reserved.

AB - 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 (R-1 = 5.0 min) with good intra- and inter-day reproducibility and limits of detection and quantification found to be 0.01 and 0.04 mug 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 It 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. (C) 2004 Elsevier B.V. All rights reserved.

KW - Pyrazine 2

KW - 5-dipropionic acid

KW - 5-Aminolevulinic acid

KW - Photodynamic therapy

KW - Drug delivery

KW - Assay validation

KW - Degradation

M3 - Article

VL - 36

SP - 1099

EP - 1105

JO - Journal of Pharmaceutical and Biomedical Analysis

T2 - Journal of Pharmaceutical and Biomedical Analysis

JF - Journal of Pharmaceutical and Biomedical Analysis

SN - 0731-7085

IS - 5

ER -