Positron emission tomography (PET) is a useful technology that enables one to obtain in vivo biological information quantitatively and non-invasively using a wide variety of radiopharmaceuticals with short-lived β + -emitting radionuclide (e.g. 11 C, t1/2 = 20.39 min). The specific radioactivity, the ratio between the radioactivity and chemical mass of radiolabeled and unlabeled compounds (Bq/mol), is one of the most important factors to assure the quality and safety of a clinical PET study. In particular, an accurate measurement of the specific radioactivity is vital to the analysis of PET imaging data for saturable processes where unlabeled ligand or substrate will compete with the radioligand at the target receptor, transporter or enzyme.The HPLC method with UV detection is most commonly used to analyze the mass concentration, and has been described in the USP as the recommended method for PET radiopharmaceuticals, such as [ 11 C]Flumazenil, N-[ 11 C]Methylspiperone and [11 C]Raclopride; 1 however, it does not always provide sufficient sensitivity since its short half-life could result in a high specific radioactivity of synthetic products. PET compounds often fall to an extremely low level (ng -μg/mL) in pharmaceutical fluids. Recently, the HPLC method coupled with mass spectrometry (MS) has been utilized in the analysis of PET radiopharmaceutical [2][3][4] and is reported to be sensitive compared to UV detection. However, this method requires quite expensive equipment; thus, it is not suitable for the routine analysis of PET radiopharmaceuticals.Chemiluminescence (CL) detection offers an attractive method due to its low detection limit with relatively simple instrumentation. Ru(bpy)3 2+ is one of the most frequently used reagent and is applied to the determination of oxalate, 5 active methylenes, 6 indoles, 7 aliphatic tertiary amines, 8 Various methods have been employed to obtain the active oxidized reagent Ru(bpy)3 3+ .These include chemical, photochemical and electrogenerated CL. The electrogenarated Ru(bpy)3 2+ CL method is most widely used for quantitative analysis; however, it has certain limitation including electrode fouling and the need to recondition the electrode surface to retain sensitivity. 13 The chemically prepared Ru(bpy)3 3+ method has the advantages of reproducibility, simplicity and cost performance.Recently, some papers have appeared on analytically successful applications utilizing chemically prepared Ru(bpy)3 3+ by flow injection assay (FIA). 14-17 Many PET compounds, commonly used in clinical studies, contain the aliphatic or alicyclic amine functional group, which can be detected by the Ru(bpy)3 2+ CL reaction without prior Sciences, Fukuoka University, Nanakuma, Johnan, Japan A sensitive, selective and rapid high-performance liquid chromatographic (HPLC) method with chemiluminescence (CL) detection was developed and validated for the analysis of positron emission tomography (PET) radiopharmaceuticals. This method is based on the CL reaction of PET compounds with tris(2,2′-bip...