On the use of liquid chromatography with radio- and ultraviolet absorbance detection coupled to mass spectrometry for improved sensitivity and selectivity in determination of specific radioactivity of radiopharmaceuticals

Abstract

Pneumatically assisted electrospray mass spectrometry was evaluated as a complementary detection technique to UV absorbance, for determination of specific radioactivity of tracer molecules to be used in positron emission tomography. Tracers labelled with radionuclides having short half-lives can be synthesised with high specific radioactivity. The UV absorbance detection that is commonly used for the determination does not always have the sensitivity required for those analyses. In comparison, mass spectrometry gave improved detection limits in all but one (nicotine) of the 12 compounds studied. The magnitude of this improvement was more than 100-fold for the compounds ketamine (2-methylamino-2-(2-chloro-phenyl)cyclohexanone), SCH-23390 (( R)-(+)-7-chloro-8-hydroxy-1-methyl-1-phenyl-2,3,4,5-tetra-hydro-1 H-3-benzazepine) and N-methyl-piperidylbenzilate. These improved detection limits, specificity, plus the added certainty of product identity provided by mass spectral data demonstrated the value of the mass spectrometer as a complementary detector in the determination of specific radioactivity.