Development and validation of a high-performance liquid chromatography tandem mass spectrometry method for the quantification of the antiparasitic and antifungal drug amphotericin B in human skin tissue.

Autor: Roseboom IC; Department of Pharmacy & Pharmacology, Antoni van Leeuwenhoek Hospital/The Netherlands Cancer Institute, Amsterdam, the Netherlands; Department of Pharmaceutical Sciences, Faculty of Science, Utrecht University, Utrecht, the Netherlands. Electronic address: i.roseboom@nki.nl., Thijssen B; Department of Pharmacy & Pharmacology, Antoni van Leeuwenhoek Hospital/The Netherlands Cancer Institute, Amsterdam, the Netherlands., Rosing H; Department of Pharmacy & Pharmacology, Antoni van Leeuwenhoek Hospital/The Netherlands Cancer Institute, Amsterdam, the Netherlands., Alves F; Drugs for Neglected Diseases Initiative, Geneva, Switzerland., Sundar S; Institute of Medical Sciences, Banaras Hindu University, Varanasi, Uttar Pradesh, India., Beijnen JH; Department of Pharmacy & Pharmacology, Antoni van Leeuwenhoek Hospital/The Netherlands Cancer Institute, Amsterdam, the Netherlands; Department of Pharmaceutical Sciences, Faculty of Science, Utrecht University, Utrecht, the Netherlands., Dorlo TPC; Department of Pharmacy & Pharmacology, Antoni van Leeuwenhoek Hospital/The Netherlands Cancer Institute, Amsterdam, the Netherlands. Electronic address: t.dorlo@nki.nl.
Jazyk: angličtina
Zdroj: Journal of chromatography. B, Analytical technologies in the biomedical and life sciences [J Chromatogr B Analyt Technol Biomed Life Sci] 2022 Aug 15; Vol. 1206, pp. 123354. Date of Electronic Publication: 2022 Jul 04.
DOI: 10.1016/j.jchromb.2022.123354
Abstrakt: Amphotericin B is an antifungal and antiparasitic drug used in first-line treatment of the parasitic neglected tropical disease leishmaniasis. Liposomal amphotericin B is currently studied for the treatment of cutaneous and post-kala-azar dermal leishmaniasis, where the dermis of the skin is infected with Leishmania parasites. For the optimization of known treatment regimens, accurate target-site concentrations of the drug are required. To date, no assay was available to assess human skin concentrations of amphotericin B. We here present a bioanalytical assay for the quantification of amphotericin B in 4-mm human skin biopsies. Human skin biopsies were homogenized by overnight digestion using collagenase A and were processed afterwards by simple protein precipitation using methanol. Separation and detection were achieved using a Gemini C18 column with slightly acidic chromatographic conditions and a quadrupole - linear ion trap mass spectrometer, respectively. The method was validated in digestion solution over a range of 10-2,000 ng/mL using natamycin as internal standard, with a correlation coefficient (r 2 ) of at least 0.9974. The assay performance, accuracy and precision, were acceptable over the validated range, using international (EMA and FDA) acceptance criteria. In the skin tissue extracts, amphotericin B ion enhancement was observed, however, the internal standard (IS) corrected for this effect hence calibration standards in digestion solvent could be used as a surrogate matrix for the quantification in skin tissue. Sample preparation recoveries were low (around 27%) because of degradation of amphotericin B during digestion and sample preparation processes, albeit highly reproducible, without compromising the accuracy and precision of the method. Using this assay, amphotericin B could be detected and quantified in skin biopsies originating from treated Indian post-kala-azar dermal leishmaniasis patients.
(Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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