ArticleScientific reports2025
Protoporphyrin IX plasma and blood pharmacokinetics and brain tumor distribution determined by a validated LC-MS/MS method.
Article in Scientific reports, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
2 citing papers in PubMed.
- The Queen and the Dark Twin: Heme, Protoporphyrin IX, and State Transitions in Liver Metabolism.Molecules (Basel, Switzerland) · 2026Review
- Analysis of porphyrins from serum and the benefit of inert biphenyl columns for liquid chromatography separation.PloS one · 2026Article
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Authors and funding
5 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Protoporphyrin IX (PPIX) is a fluorescent metabolite in the heme biosynthesis pathway, and cancer cells accumulate it when 5-aminolevulinic acid (5-ALA), a precursor, is administered. In the U.S., 5-ALA is approved for visualizing high-grade gliomas (HGG) during fluorescence-guided surgery. PPIX is also central to experimental photodynamic and sonodynamic therapies for HGG. Additionally, PPIX measurement is critical for diagnosing and monitoring porphyrias. Despite the need for a sensitive and rapid bioanalytical method for accurate quantification of PPIX in biospecimens, no reliable validation of an LC-MS/MS method is available due to challenges related to its chemical instability, poor solubility, and tendency to aggregate. This work is the first to present a fully validated, sensitive, and rapid LC-MS/MS method for determining PPIX levels in human plasma, blood, and brain tumors. The method overcomes stability concerns, achieving a 3.5-min total run-time with a concentration range of 1-2000 nmol/L for plasma and tumors, and 10-2000 nmol/L for blood. Application of the method in a clinical trial, which assesses sonodynamic therapy for HGG patients, shows significant PPIX production, peaking in plasma and blood six hours post-5-ALA administration. In recurrent HGG patients, PPIX levels were notably higher in gadolinium-enhancing tumor regions compared to non-enhancing areas, indicating preferential accumulation in tumors.
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Registered trials
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