The rapid growth of khat use and misuse in the countries of its origin and other parts ofrnthe world has led to the development of methods for extraction, clean-up, detection andrnquantification of its psychoactive alkaloids and other nutrients. However, the extractionrnand clean-up methods reported so far have a number of drawbacks and there is paucity ofrnquality data with regard to the concentrations of its psychoactive alkaloids, phenolicrncompounds and mineral nutrients of Ethiopian khat accessions. Thus, this studyrnaddressed some of the challenges facing researchers in the area, such as the need to userneasily accessible, simple, fast and plausible sample preparation techniques for khatrnalkaloids and tannins analysis. Furthermore, total polyphenols, selected essential andrnnon-essential elements and fluoride accumulation in various khat cultivars were alsorninvestigated.rnMatrix solid phase dispersion (MSPD), molecularly imprinted polymer for solid phasernextraction (MIP-SPE) and the modified quick, easy, cheap, effective, rugged and safern(QuEChERS) based methods were investigated for extraction and clean-up of khatrnalkaloids prior to HPLC-DAD detection. Under optimum conditions, good recoveries,rnselectivity and reproducibility were obtained.rnThere was an assertion that drying khat leaves could significantly (if not completely)rndecompose cathinone to cathine. However, this study demonstrated that cathinone wasrnrnpersistently existed in dried plant material and it is wrong to assume that sun or ovenrndrying the leaves could completely convert cathinone to cathine.rnThis study also presents the quantitative determination of total phenolic compounds,rnflavonoids, tannins and their related in-vitro antioxidant activities of the young leaves,rnmatured leaves and tips of tender stem near the young shoots. Simplified, rapid andrnrobust method was also developed for the analysis of total tannins using egg albumin as arnprecipitating agent and Folin Denis reagent and FeCl3 solution for color developingrnmoieties for spectrophotometric assay.rnIn addition, the concentrations of selected major, minor and toxic metals as well asrnfluoride distribution in various khat cultivars and the corresponding soil samples wererninvestigated by flame atomic absorption spectrometry and fluoride ion-selective electrodernpotentiometry, respectively. It was noticed that khat leaves could be a good sources ofrnmost of essential mineral nutrients and free from toxic metals like Pb and Cd. Analysis ofrnfluoride in the edible portion of the khat leaves resolved the equivocal information aboutrnkhat chewing and dental staining due to fluoride. It was found that the plant accumulatedrnsignificantly lower concentrations of fluoride compared with similar stimulant plants.