In the production of radioligands for imaging low concentrations of target proteins (e.g. receptors or transporters) in human subjects with positron emission tomography, control of specific radioactivity is necessary for efficacy and safety. Such quality control requires a fast method to be available for measuring carrier (non-radioactive ligand) in each batch of radioligand, preceding its release for administration. Measurement is usually achieved with HPLC equipped with an ultraviolet (UV) absorbance detector. However, this method is not easily applicable to radioligands that have low UV extinction coefficients and are produced at high specific radioactivity, such as [18F] (2β-carbomethoxy-3β-(4-chlorophenyl)-8-(2-fluoroethyl)nortropane; [18F]FECNT). Here we describe a fast, specific and sensitive LC–MS–MS method for measuring carrier in [18F]FECNT preparations. Small samples of formulated [18F]FECNT plus an added internal standard (2β-carbomethoxy-3β-(4-chlorophenyl)-8-(n-propyl)nortropane; INTSTD) are rapidly eluted from a short reverse phase HPLC column into an MS probe. Following electrospray ionization, the molecular ions ([MH]+) of FECNT (m/z=326) and INTSTD (m/z=322) are isolated and energized for collision-induced dissociation. The product ions from FECNT (m/z=294) and INTSTD (m/z=290) are monitored selectively. The calibration curve for MS response is linear for FECNT concentrations in the range 2–20 pg/µl and suitable for reproducibly (RSD 5%) and rapidly (<3 min) measuring low concentrations of carrier in [18F]FECNT preparations. Copyright © 2005 John Wiley & Sons, Ltd.