Determination of Blood Plasma Levels of Hydrazine Derivatives of Isonicotinic Acid

¹ Hoffmann-La Roche, Inc., Nutley, New Jersey.

A colorimetric method is presented for the determination of blood plasma levels of isonicotinic acid and its derivatives, the hydrazide (Rimifon) and the isopropyl hydrazide (Marsilid). The method is based on the reaction of isonicotinic acid with cyanogen bromide and ammonia. The hydrazide derivatives, which yield relatively slight color per se, are converted to isonicotinic acid by treatment of the protein-free plasma with permanganate. Plasma levels over a 24-hour period after a single oral dose are presented for dogs given 3.5, 7 or 14 mg. per kilogram of Rimifon or Marsilid and for humans receiving up to 3.4 mg. of Rimifon or 3.2 mg. of Marsilid per kilogram. In these limited trials maximum plasma levels are usually found within one-half to two hours after dose and decline rapidly. No significant amount of either compound was found in the plasma after 24 hours.