CONTAMINATION OF HEPARIN BY HISTAMINE - MEASUREMENT AND CHARACTERIZATION BY HIGH-PERFORMANCE LIQUID-CHROMATOGRAPHY AND RADIOIMMUNOASSAY

Plasma samples which were collected in the presence of heparin contained 12.83 +/- 0.34 ng/ml histamine-immunoreactive material (n = 10). In contrast, histamine-immunoreactive material in plasma samples which were collected in the presence of EDTA/phenanthroline contained 0.32 +/- 0.01 ng/ml (n = 10). Histamine-immunoreactive material was found as a contaminant in three different heparin formulations with unrelated batch numbers. The concentrations of the histamine-like material were 32.82, 81.93, and 280.23 ng/ml, respectively. Octadecasilyl-silica (ODS) cartridges were used to purify histamine from other constituents in the heparin preparations. The histamine-immunoreactive material in the three preparations could be characterized as histamine with cation-exchange high-performance liquid chromatography (HPLC) on a TSK SP-5 PW column with NaH2PO4, pH5.0, as a mobile phase and gradient elution. For the accurate measurement of histamine in plasma samples with heparin as an anticoagulant, one should be aware of a possible contamination of heparin formulations by histamine.