A sensitive method for determination of COL-3, a chemically modified tetracycline, in human plasma using high-performance liquid chromatography and ultraviolet detection

Michelle A. Rudek, Carol Hartke, Yelena Zabelina, Ming Zhao, Pamela New, Sharyn D. Baker

Research output: Contribution to journalArticle

4 Scopus citations

Abstract

COL-3, 6-deoxy-6-desmethyl-4-desdimethylamino-tetracycline, is a matrix metalloproteinase inhibitor currently in clinical development. A HPLC-UV method to quantitate COL-3 in human plasma was developed. COL-3 was extracted from plasma using solid-phase extraction cartridges. COL-3 is separated on a Waters Symmetry Shield RP8 (3.9 mm × 150 mm, 5 μm) column with EDTA (0.001 M) in sodium acetate (0.01 M, pH 3.5)-acetonitrile mobile phase using a gradient profile at a flow rate of 1 ml/min for 22 min. Carryover was eliminated by using an extended needle wash of methanol:acetonitrile:dichloromethane (1:1:1, v/v/v). Detection of COL-3 and the internal standard, chrysin, was observed at 350 nm. COL-3 and chrysin elute at 8.9 and 9.9 min, respectively. The lower limit of quantitation in human plasma of COL-3 was 75 ng/ml, linearity was observed from 75 to 10,000 ng/ml. A 30,000 ng/ml sample that was diluted 1:50 with plasma was accurately quantitated. This method is rapid, widely applicable, and suitable for quantifying COL-3 in patient samples enabling further clinical pharmacology characterization of COL-3.

Original languageEnglish (US)
Pages (from-to)751-756
Number of pages6
JournalJournal of Pharmaceutical and Biomedical Analysis
Volume37
Issue number4
DOIs
StatePublished - Apr 1 2005

Keywords

  • COL-3
  • HPLC
  • Matrix metalloproteinase inhibitor
  • Pharmacokinetics
  • Tetracycline

ASJC Scopus subject areas

  • Analytical Chemistry
  • Pharmaceutical Science

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