We present in this case report a validated method for accurate quantitative analysis of 3-methoxy phencyclidine (3-MeO-PCP) to determine postmortem blood concentrations of this PCP analog. A 29-year-old male with a history of illicit drug use was found unresponsive in his bed with a bag of white powder next to him. Resuscitation efforts were unsuccessful and the individual was pronounced dead 9 minutes after arrival to the hospital. Initial ELISA screening suggested the presence of PCP in the decedent’s blood. However, confirmatory testing revealed no detectable PCP. Instead, a large peak corresponding to a m/z 274.218 species with retention time similar to PCP was present on a LC-TOF-MS drug screen, suggesting a possible PCP analog. This mass corresponds specifically to a methoxy-PCP analog, several of which are available for purchase online. Standards for 3-MeO-PCP and 4-MeO-PCP were obtained and injected on the same instrument. Although the 3- and 4-MeO-PCP analogs have identical masses and retention times, they are still distinguishable through their mass spectra. The peak from the decedent’s sample matched both the mass spectrum and the retention time of 3-MeO-PCP. A quantitative LC–MS-MS method was subsequently developed and validated for casework. Analysis using this method revealed a concentration of 139 ± 41 µg/L 3-MeO-PCP in the decedent’s blood. Diphenhydramine (4.1 ± 0.7 mg/L), marijuana metabolite (presumptive positive, confirmation not performed) and a small amount of amphetamine (<0.10 mg/L) were also found in the decedent’s blood. The cause of death was determined to be combined 3-MeO-PCP, diphenhydramine and amphetamine toxicity. The manner of death was certified as an accident.