Radiographic contrast agents (RCAs) opacify internal vessels and cavities of the body to x-rays providing diagnostic information to physicians. These radiopaque compounds contain iodine which absorbs x-rays and allows visualization of high contrast images. Large doses of these agents are injected into a bodily fluid, typically blood or spinal fluid, for contrast enhancement. Adverse reactions of recipients to these agents have been reported, ranging from mild to lethal effects. For some widely used agents the risk and cost factors are inversely related to each other. For certain procedures the more expensive agent is appropriate to minimise life-threatening toxic reactions. There have been cases, particularly involving injection of RCA into cerebrospinal fluid (CSF), in this category where death has occurred and coronial inquests have required that the identity of the agent used be verified by analysis of the bodily fluids of the deceased. The RCAs in this case (below) were not amenable to clear separation by liquid chromatography and conventional mass spectrometry also failed due to the thermal lability of the compounds.

We have developed a method for detection and identification of these RCAs whereby CSF samples (from sheep) spiked with trace levels of angiographin (I) or iopamidol (II) are first cleaned up using using Sep-pak C18 cartridge containing chemically bonded silica groups. The C18 cartridge functions as a "chemical filter" by retaining the desired component while letting the unwanted components elute or by retaining components that interfere and letting the desired component elute. The C18 cartridge is nonpolar and it follows the principles of reversed-phase chromatography. The eluate was injected into the electrospray ion source and MS1 was set to transmit (and monitor) the parent ion [M+1]⁺ of II or the [M+1]⁺ ion of diatrizoic acid (i.e., the doubly protonated anion of I). MS2 was set to transmit and monitor the most abundant collisionally induced daughter ion of the parents in each case. Good linearity was observed for samples in the range 1pM/µL to 200pM/µL (approximately 1 to 200 ppm). Better detection limits indicated were using the MS/MS method.