title: Highly sensitive potentiometric strip test for detecting high charge density impurities in heparin.
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.
authors.affiliation: Department of Chemistry, Kwangwoon University, Seoul 139-701, Korea.
authors.forename: Youngjea
authors.initials: Y
authors.lastname: Kang
authors.forename: Kihak
authors.initials: K
authors.lastname: Gwon
authors.forename: Jae Ho
authors.initials: JH
authors.lastname: Shin
authors.forename: Hakhyun
authors.initials: H
authors.lastname: Nam
authors.forename: Mark E
authors.initials: ME
authors.lastname: Meyerhoff
authors.forename: Geun Sig
authors.initials: GS
authors.lastname: Cha
mesh_terms: D002809:Chondroitin Sulfates / Q000032:analysis*; D055664:Electrochemical Techniques / Q000379:methods*; D004566:Electrodes; D006493:Heparin / Q000737:chemistry*; D008280:Magnetics; D046210:Microfluidic Analytical Techniques / Q000379:methods; D000071228:Polyelectrolytes; D011108:Polymers / Q000737:chemistry; D011143:Polyvinyl Chloride / Q000737:chemistry; D000644:Quaternary Ammonium Compounds / Q000737:chemistry
chemical_list: D002809:Chondroitin Sulfates; D006493:Heparin; D000071228:Polyelectrolytes; D011108:Polymers; D011143:Polyvinyl Chloride; D000644:Quaternary Ammonium Compounds; C009543:tridodecylmethylammonium