Urine drug testing plays an important role in detecting licit and illicit drug use. Adulteration of urine samples have been employed to disrupt these drug tests. Recently, zinc sulfate was used as an effective adulterant to bypass drug testing. Aim of the work: The aim of the current study was to evaluate the effect of zinc sulfate and some adulteration methods on detection of tramadol and apetryl in urine and their effects on the validity tests. Method: Tramadol and apetryl were added to urine sample that were obtained from a healthy, drug-free subject to yield samples of urine containing tramadol and apetryl with concentrations (200 ng/ ml & 400 ng/ ml). Visine eye drop, zinc sulfate and lemon were added to these samples as well as dilution was done. These samples were tested for their ability to generate false negative results for the immunoassay test screen. Results: All adulterated urine samples as regard both drugs generated false negatives results. PH paper test showed more acidic PH with lemon juice while visine, zinc sulfate and dilution gave light green coloration indicating slightly acidic PH. Specific gravity showed increase of specific gravity for urine adulterated with lemon but decrease in diluted urine. Conclusion: There are needs to a more effective and efficient approach to urinalysis due to the false negatives that can result from adulteration of urine samples.