Highly sensitive potentiometric strip test for detecting high charge density impurities in heparin

Anal Chem. 2011 May 15;83(10):3957-62. doi: 10.1021/ac103090m. Epub 2011 Apr 18.

Abstract

Contamination of heparin with oversulfated chondroitin sulfate (OSCS) became a matter of grave concern in the medical field after many fatal responses to OSCS tainted heparin products occurred during the 2007-2008 period. Even though standard lab-based analytical techniques such as nuclear magnetic resonance (NMR) and strong anion-exchange high performance liquid chromatography (SAX-HPLC) have proven useful for monitoring the OSCS content in heparin products, an easy-to-use, quick, portable, and cost-efficient method is still needed for on-site monitoring during and after the heparin production. In this report, a disposable strip-type electrochemical polyion sensor is described for detection of low levels of OSCS contamination in heparin. A magnetic actuator is incorporated into this simple electrode-based microfluidic device in order to create the mixing effect necessary to achieve equilibrium potential changes of the sensor within a microfluidic channel. The planar membrane electrode detector within the sample channel is prepared with a tridodecylmethylammonium chloride (TDMAC)-doped poly(vinyl chloride) (PVC) membrane essentially equivalent to previously reported polyanion-sensitive electrodes. When the concentration of heparin applied to the single-use strip device is 57 mg/mL (in only 20 μL of sample), the same concentration recommended in the NMR analysis protocol for detecting OSCS in heparin, the detection limit is 0.005 wt % of OSCS, which is ca. 20 times lower than the reported detection limit of the NMR method.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Chondroitin Sulfates / analysis*
  • Electrochemical Techniques / methods*
  • Electrodes
  • Heparin / chemistry*
  • Magnetics
  • Microfluidic Analytical Techniques / methods
  • Polyelectrolytes
  • Polymers / chemistry
  • Polyvinyl Chloride / chemistry
  • Quaternary Ammonium Compounds / chemistry

Substances

  • Polyelectrolytes
  • Polymers
  • Quaternary Ammonium Compounds
  • polyanions
  • tridodecylmethylammonium
  • Polyvinyl Chloride
  • Heparin
  • Chondroitin Sulfates