The simultaneous monitoring of plasma levels of neostigmine and pyridostigmine in man.

The synthesis of a series of pyridostigmine analogues wa reported. From these analogues N,N-dipropylcarbamoyloxy-1-methylpyridinium bromide was considered the most suitable compound for use as a common internal marker for the simultaneous determination of neostigmine and pyridostigmine in human plasma. The assay involved a preliminary ion-pair extraction of the drugs and the internal marker from plasma using potassium-iodide glycine buffer. The extract was analysed by a GC system (10% OV-17 on chromosorb W-AW, 100-120 mesh) linked to a nitrogensensitive detector. The calibration graphs of neostigmine and pyridostigmine were linear and reproducible over the range 5 ng to 100 ng per ml in 3 ml plasma samples. This assay procedure has been used to monitor simultaneously the plasma levels of neostigmine (4.7 to 33 ng per ml) and pyridostigmine (2.7 to 18.6 ng per ml) of a myasthenic patient over a period of twelve hours with repeated dosing of neostigmine bromide (30 mg) and pyridostigmine bromide (60 mg).