Transition-metal mediated carbonylation with C-labelled carbon monoxide ([ C]CO) is a versatile method for introducing C (t = 20.3 min) into drugs and radioligands for subsequent use in positron emission tomography (PET). The aim of the current study was to perform the C-carbonylation reaction on the interior surface of a stainless-steel loop used for high performance liquid chromatography (HPLC). In the experimental setup, cyclotron produced C-labelled carbon dioxide ([ C]CO ) was converted to [ C]CO by reduction over heated Molybdenum and swept into an HPLC loop pre-charged with the appropriate reaction mixture. Following a 5 min reaction, the radiochemical purity (RCP) and the trapping efficiency (TE) of the reaction mixture was determined. After optimization, [ C]N-Benzylbenzamide was obtained in quantitative radiochemical yield (RCY) following a 5 min reaction at room temperature. The methodology was further applied to label [ C]benzoic acid (RCP≥99%, TE>91%), [ C]methyl benzoate (RCP≥99%, TE>93%) and [ C]phtalide (RCP≥99%, TE>88%). A set of pharmaceuticals was finally radiolabelled using non-optimized conditions. Excellent yields were obtained for the histamine-3 receptor radioligand [ C]AZ13198083, the oncology drug [ C]olaparib and the dopamine D2 receptor radioligand [ C]raclopride, whereas a moderate yield was observed for the high-affinity dopamine D2 receptor radioligand [ C]FLB457. The presented "in-loop" process proved efficient for diverse C-carbonylations, providing [ C]amides, [ C]esters and [ C]carboxylic acids in moderate to excellent RCYs. Based on the advantages associated with performing the radiolabelling step as an integrated part of the purification system, this methodology may become a valuable addition to the toolbox of methodologies used for C-carbonylation of drugs and radioligands for PET.