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Improved method for quantitative analysis of the cyclotide kalata B1 in plasma and brain homogenate
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry, Division of Pharmacognosy.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry, Division of Pharmacognosy.
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2016 (English)In: Biopolymers, ISSN 0006-3525, E-ISSN 1097-0282, Vol. 106, no 6, 910-916 p.Article in journal, Meeting abstract (Refereed) Published
Abstract [en]

This study provides a new method for quantifying the cyclotide kalata B1 in both plasma and brain homogenate. Cyclotides are ultra-stable peptides with three disulfide bonds that are interesting from a drug development perspective as they can be used as scaffolds. In this study we describe a new validated LC-MS/MS method with high sensitivity and specificity for kalata B1. The limit of quantification was 2 ng/mL in plasma and 5 ng/gmL in brain homogenate. The method was linear in the range 2-10,000 ng/mL for plasma and 5-2000 ng/g for brain. Liquid Chromatographic separation was performed on a HyPurity C18 column, 50 3 4.6 mm, 3 mm particle size. The method had inter-and intra-day precision and accuracy levels <15% and 12% respectively. Applying the method to in vivo plasma samples and brain homogenate samples from equilibrium dialysis yielded satisfying results and was able to describe the plasma pharmacokinetics and brain tissue binding of kalata B1. The described method is quick, reproducible and well suited to quantifying kalata B1 in biological matrices.

Place, publisher, year, edition, pages
2016. Vol. 106, no 6, 910-916 p.
Keyword [en]
brain, cyclotides, kalata B1, liquid chromatography, mass spectrometry, pharmacokinetics
National Category
Medicinal Chemistry
Identifiers
URN: urn:nbn:se:uu:diva-317707DOI: 10.1002/bip.22984ISI: 000393465500016PubMedID: 27603276OAI: oai:DiVA.org:uu-317707DiVA: diva2:1082634
Conference
3rd International Conference on Circular Proteins (ICCP), NOV 01-04, 2015, AUSTRALIA
Funder
Swedish Research Council, 2012-5063 2011-4339
Available from: 2017-03-17 Created: 2017-03-17 Last updated: 2017-03-17Bibliographically approved

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Melander, ErikEriksson, CamillaJansson, BrittGöransson, UlfHammarlund-Udenaes, Margareta
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Department of Pharmaceutical BiosciencesDivision of Pharmacognosy
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