Determination of physostigmine and pyridostigmine in pharmaceutical formulations by capillary electrophoresis.

Abstract

Physostigmine (PHY) and pyridostigmine (PYR) are two important anticholinesterase compounds with several clinical uses. Recently, PHY has been investigated for the treatment of senile dementia in Alzheimer's disease. However, both PHY and PYR have gained importance as antidotes for anticholinergic drugs. In military medicine, PYR is used as a prophylactic against nerve gas poisoning and was used in Saudi Arabia during the Gulf War in 1991. A new capillary zone electrophoresis (CZE) method for the rapid determination of PHY and PYR in pharmaceutical preparations has been developed. An untreated fused-silica capillary tube (75 microm i.d., 44 cm total length, 36.5 cm length to the detector) was employed with detection at 200 and 270 nm for PHY and PYR, respectively. The optimal separation conditions for PHY were: 50 mM boric acid-HCl buffer (pH 3.25) with 30 mM NaClO4, electrokinetic injection for 5 sec at -5 kV, temperature 25 degrees C, and separation voltage 15 kV. The optimal separation conditions for PYR were: 20 mM phosphate buffer (pH 7), electrokinetic injection for 20 sec at -10 kV, temperature 25 degrees C, and separation voltage 15 kV. The limits of detection (LOD, S/N = 3) were 70 and 60 ppb for PHY and PYR, respectively. The method can be used for the monitoring of possible main degradation products in tablets of military antidote formulations.