A sensitive and selective method for the determination of 4’-ethyl-3-methyl-3-piperidinopropiophenone hydrochloride (eperisone hydrochloride) in human plasma was developed and validated The procedure employed an internal standard and a solvent extraction step followed by chromatography on a Xterra $C_{18}$ minibore column. Detection was by electrospray ionization tandem mass spectrometry with multiple reaction monitoring. The mass transitions of eperisone and tolperisone (IS) were m/z 260 ${ ightarrow}$ 98 and m/z 246 ${ ightarrow}$ 98, respectively. The method has a limit of detection of 0.1 pg/mL for eperisone based on the three times signal-tonoise value with a linear range from 0.01 to 10.0 ng/mL for the analyte. Extraction recovery was on average 98.6${pm}$7.2% (SD) for eperisone. The Intra- and inter-day assay accuracy ranged from 93 to 114% and precision (RSD) was better than 8.5%. The method was successfully employed to analyze plasma samples and evaluate pharmacokinetics of eperisone in healthy male volunteers.