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A simple method is presented for the simultaneous determination of morphine, 6-acetylmorphine, codeine, cocaine, benzoylecgonine, cocaethylene, methadone and 2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine (EDDP) in vitreous humor by high-performance liquid chromatography with photodiode array detector after solid-phase extraction with Oasis (R) HLB cartridges and dichloromethane as eluent. The chromatographic process was carried out using an XTerra (R) RP8 column (250x4.6mm i.d., 5 mu m particle size) and a mobile phase composed of acetonitrile and pH 6.5 phosphate buffer in gradient mode. A linear response from the detector was obtained within the concentration range of 0.1-4 mu g ml-1, with correlation coefficients higher than 0.99. The limits of detection were lower than 30ng ml-1 for all the drugs studied, the coefficients of variation fluctuated between 0.1 and 12.4%, and the average recoveries were higher than 78% for all the drugs except for EDDP, with a value of 66.4%. Finally, the proposed method was applied to 15 vitreous humor samples coming from individuals who had died from opiate and/or cocaine overdose, showing consumption of cocaine in 14 cases, methadone in five cases and heroin in three cases. Average concentrations of 0.30 mu g ml-1 for morphine, 0.24 mu g ml-1 for 6-acetylmorphine, 0.10 mu g ml-1 for codeine, 0.81 mu g ml-1 for cocaine, 1.26 mu g ml-1 for benzoylecgonine, 0.15 mu g ml-1 for cocaethylene, 0.11 mu g ml-1 for methadone and 0.68 mu g ml-1 for EDDP were obtained. Copyright (c) 2012 John Wiley & Sons, Ltd.