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Determinationof Physostigminein Plasma and with ElectrochemicalDetection

Physostigmine (Phy) was determined in plasma and cerebrospinal fluid (CSF) by HPLC with electrochemical detection, with use of a normal-phasecolumn and methanolic sodium acetate buffer, pH 4.6. The detection limit of the method was 0.5 ig/L for a 2-mL sample of plasma or 0.5 mL of CSF. Analytical recovery of Phy in the range from 0.5 to 40 ,ug/L was 60% (SD 5%) for plasma and 78% (SD 8%) for CSF. Excellent chromatographic separation of Phy without column deterioration during extended usage and constant recovery for a wide range of Phy concentrations makes the routine monitoringof plasma from patients with Alzheimer’s disease economically feasible. Using our method, we measured Phy in 13 such patients’ plasmas at 105 and 135 mm after a 135mm Intravenous infusion of 300, 600, and 900 zg of Phy per square meter of body surface. Mean values significantly Increased with dose (P = 0.001), but differences between 105 and 135 mm (P = 0.229) or between dose and time (P = 0.949) were not significant.