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Determination of 8-methoxypsoralen levels in plasma and skin suction blister fluid by a new sensitive fluorodensitometric method

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Summary

An improved fluorodensitometric assay for the determination of 8-methoxypsoralen (8-MOP) in plasma is described. Because of its low limit of detection (below 1 ng/spot) this method is suitable to determine the drug in skin suction blister fluid, too. The standard deviation of the procedure is 6.4% or less.

Plasma and skin blister fluid levels of 8-MOP are determined 2 h following oral administration of 40–60 mg 8-MOP. They range from 0–239 ng/ml and 0–163 ng/ml, respectively. A rather close correlation (r=0.91) between these two parameters could be observed.

Thus, in cases with relatively high plasma levels sufficient skin levels can be predicted. If further investigations would prove, however, that a distinct concentration threshold required for therapeutic success exists — and recent experiments with fibroblast cultures imply that — skin blister fluid level determinations would seem highly desirable when plasma levels let us expect skin levels in the critical range.

In general determination of 8-MOP skin blister fluid levels can be looked upon as a model for the evaluation of drug skin levels after systemic application in man.

Zusammenfassung

Es wird ein verbessertes dünnschichtchromatographisches fluorimetrisches Bestimmungsverfahren für 8-Methoxypsoralen (8-MOP) im Plasma beschrieben. Wegen ihrer niedrigen Nachweisgrenze eignet sich die Methode auch zur Bestimmung von 8-MOP in Saugblasenflüssigkeit. Ihre Standardabweichung liegt bei 6,4% oder darunter.

Die Plasma- und Hautblasenflüssigkeitsspiegel von 8-MOP werden 2 h nach oraler Aufnahme von 40–60 mg bestimmt. Sie schwanken zwischen 0 und 239 ng/ml bzw. 0 und 163 ng/ml. Die Korrelation (r=0,91) zwischen diesen beiden Parametern erweist sich als relativ eng.

Demzufolge können die Hautspiegel in Fällen mit relativ hohen Plasmaspiegeln geschätzt werden. Sollten weitere Untersuchungen jedoch zeigen, daß es eine bestimmte, für den therapeutischen Erfolg notwendige Minimalkonzentration gibt — und neueste Untersuchungen an Fibroblastenkulturen weisen in diese Richtung —, so erscheinen Hautblasenflüssigkeitsspiegelbestimmungen bei denjenigen Patienten besonders wünschenswert, deren Plasmaspiegel Hautspiegel im kritischen Bereich erwarten lassen.

Ganz allgemein kann die Bestimmung von Hautblasenflüssigkeitsspiegeln als Modell für die Bestimmung von Arzneimittelhautspiegeln nach systemischer Gabe beim Menschen angesehen werden.

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Authors and Affiliations

  1. Dept. of Dermatology, Faculty of Medicine, University of München, Frauenlobstr. 9-11, D-8000, München 2, Germany

    H. Ch. Korting & E. Roser-Maass

  2. Dept. of Pharmacology, Faculty of Pharmacy and Biochemistry, University of Frankfurt, D-6000, Frankfurt a.M., Germany

    M. Schäfer-Korting & E. Mutschler

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  1. H. Ch. Korting
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  2. M. Schäfer-Korting
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  3. E. Roser-Maass
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  4. E. Mutschler
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Supported in part by the Deutsche Forschungsgemeinschaft and by the Doktor-Robert-Pfleger-Stiftung

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Korting, H.C., Schäfer-Korting, M., Roser-Maass, E. et al. Determination of 8-methoxypsoralen levels in plasma and skin suction blister fluid by a new sensitive fluorodensitometric method. Arch Dermatol Res 272, 9–20 (1981). https://doi.org/10.1007/BF00510388

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  • DOI: https://doi.org/10.1007/BF00510388

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