A case is presented of a 39-year-old woman who suffered severe debilitation because of a hemorrhagic stroke in the context of substance abuse. The patient presented to the emergency room with rapidly diminishing mental status, hypertension, and vasoconstriction; her friends provided a history of ingestion of cocaine, 3,4-methylenedioxymethamphetamine (MDMA), and 2C-I, a novel designer amine. A multi-targeted LC-MS/MS method for sympathomimetic amines and related drugs in urine detected and quantified 2C-I and MDA, while ruling out MDMA. The cause of the stroke was determined to be an underlying cerebrovascular abnormality called Moyamoya, secondary to substance abuse. In clinical laboratories, gas chromatography-mass spectrometry or liquid chromatography-tandem mass spectrometry (LC-MS/MS) confirmation of a positive amphetamine immunoassay is usually directed only towards amphetamine, methamphetamine, MDMA and MDA. This report demonstrates the utility of testing for a wider menu of compounds using LC-MS/MS in order to better characterize the prevalence and toxicities of novel amines such as 2C-I.