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Abstract Among the drugs abused by subjects allover the world are codeine and nalbuphine which are widely used in several pharmaceutical formulations. The present study aimed at finding a simple, quick and reliable method for the estimation of both drugs in blood and various tissues. Also the effect of both drugs on some enzymes in blood and tissues as well as the effect on cellular DNA were also a target of the present study. The modification of the HPLC method included the use of methanol : water (95 : 5 , v/v ) as a mobile phase for the estimation of codeine and methanol : water (80 : 20 , v/v ) for the estimation of nalbuphine at a flow rate 1.7 m/ min. using Zorbax NH2 4.6 (So(Bm (S(B25 cm. P.N. 880952.708 column at 17 C. A. Ch.E. activities were significantly increased in serum, brain and liver of codeinetreated rats. Significant decrease of 5NT activities was observed in kidney, liver and spleen homogenates of codeinetreated rats. Significant inhibition of 5NT activities was observed in liver and spleen homogenates while abnormal activation of the enzyme was observed in kidney homogenate of nalbuphinetreated rats. The results refer to the possibility of using the analyses of some tissues of postmortems for both drugs to reflect serum levels of these drugs, which in turn reflect the intake of the drugs. Also the activation of A.C.h.E. and decrease of 5NT activities are considered good markers for both codeine and nalbuphine overloading. |