A rapid, reproducible and sensitive reversed phase liquid chromatography–mass spectrometry method was developed and validated for the identification and semi-quantitative confirmation of stimulants in urine. The method is capable of separating compounds such as cocaine and metabolites, amphetamines, substituted cathinones and other designer drugs, with a total run time of 11 min. The method was subsequently used to confirm the presence of these stimulants in the urine of patients attending the Drug Treatment Centre Board Ireland over the period in which legislation banning some named cathinones was introduced in Ireland. Substituted cathinones were the predominant drug of choice, outside of cocaine use. Mephedrone was the most widely detected cathinone in 2010, whereas 3,4-methylenedioxypyrrolidinobutyrophenone featured more prevalently in screenings in 2011. The appearance of adverse effects increases during multi-stimulant use related to synergistic pharmacological combinations, and this method has benefits in identifying multi-drug use between next generation designer drugs and commonly used stimulants.