Analytical approaches to investigating metal-containing drugs

Many pharmaceuticals contain metals, either as part of the active compound or within the formulation. They are also found in related products such as dietary supplements and toiletries. Concentrations of metals in biological fluids or tissues from patients taking these agents, are measured where there may be an adverse reaction, dose-related toxicity or for therapeutic drug monitoring. Other situations, for analysis of environmental samples include occupational exposure (manufacture, administration to patients, pharmaceutical research) or in investigations of poisoning. Highly sensitive and accurate analytical methods are now available to determine the total metal concentration in a specific sample, but also to measure the specific chemical form of the drug, a metabolite of the drug, or the drug's interaction with important cellular components, such as DNA. The use of ICP-MS to measure total metal concentrations, or HPLC coupled to ICP-MS for the more complex speciation measurements, will depend on the type of information that is required. For the investigation of the drug species present, other complementary analytical techniques such as electrospray mass spectrometry (LC-MS/MS) are required for a full structural elucidation of the analytes. In this current publication we highlight the measurement of two metal(loid) based pharmaceutical drugs for the treatment of cancer. One 4-(N-(S-glutathionylacetyl)amino) phenylarsenoxide (GSAO) containing arsenic and under investigation for the treatment of solid tumours, and the second cis-diamminedichloroplatinum (II) (cisplatin) containing platinum and widely used in the clinical setting as a front line treatment against various neplasias in particular testicular, ovarian, bladder and head and neck cancers.