Introduction: Substance abuse becomes a global challenge with alarming increase in use of crystal meth (shabu) in Egypt. For that, there is an urgent need to develop a reliable analytical method in routine operations. Aim: The current study aimed to develop and validate of a sensitive and accurate method for methamphetamine (meth) determination in human urine to evaluate prevalence of meth in Sohag population. Methodology: The study was applied on subjects attending Sohag Clinical Toxicology Laboratory for drug abuse testing, which exhibited primary positive results for amphetamine by rapid immunoassay dipstick (ABONtm). Amphetamine-positive cases were analyzed for meth by validated method on HPLC-DAD. Tert-butylmethyl ether (MTBE) in alkaline media was used to extract meth from urine and back-extracted into hydrochloric acid where propranolol was employed as the internal standard with extraction efficiency 77.77 %. Results: The calibration curve was linear (r²> 0.99) in the concentration range from0.25 to 3 µg /mL for methamphetamine. Limits of detection and quantification were 0.1 and 0.25 µg/mL, respectively. Intra- and inter-assay precisions for meth were within 2.75& 9.70 and 1.90 & 4.87%, respectively. Intra- and inter-assay accuracies were within (-6.67) &9.33 and (-2.78) & 6.67 %., respectively. The method revealed 51 cases of meth abuse in studied subjects. Their risk assessment and drug usage association were studied.  Conclusion: The current method low limit of quantification (LOQ) of 0.25 µg/mL provides sensitive and adequate confirmatory physical evidence for the presence of meth in the urine. Recommendations: Routine meth screening is recommended viewing its increasing abuse and its hazardous health effects.