The pharmacological properties of any drug are related to their ability to interact with macromolecular blood components. The interaction of human serum albumin (HSA) and apotransferrin (ATf) with six Ru complexes containing ketoconazole (KTZ), which we have previously reported to be active against and , has been investigated by monitoring the tryptophan fluorescence intensity of each protein upon incremental addition of the complexes. All the Ru-KTZ derivatives, namely -[RuCl(DMSO)(KTZ)] (), -[RuCl(bipy)(DMSO)(KTZ)] (), [Ru(--cymene)Cl(KTZ)] (), [Ru(--cymene)(en)(KTZ)][BF] (), [Ru(--cymene)(bipy)(KTZ)][BF] (), and [Ru(--cymene)(acac)(KTZ)][BF] () are able to quench the intrinsic fluorescence of HSA and ATf at 27 °C. Analysis of the spectroscopic data using Stern-Volmer plots indicates that in both cases the quenching takes place principally through a static mechanism involving the formation of Ru complex-protein adducts; further analysis of the fluorescence data allowed the estimation of apparent association constants and the number of binding sites for each protein and each compound. The results indicate that both HSA and ATf are possible effective transporters for Ru-KTZ antiparasitic drugs.

The occurrence of harmful algal blooms in nutrient-rich freshwater bodies has increased world-wide, including in the Pacific Northwest. Some cyanobacterial genera have the potential to produce secondary metabolites that are highly toxic to humans, livestock and wildlife. Reliable methods for the detection of cyanobacterial toxins with high specificity and low limits of detection are in high demand. Here we test a relatively new hybrid high resolution accurate mass quadrupole time-of-flight mass spectrometry platform (TripleTOF) for the analysis of cyanobacterial toxins in freshwater samples. We developed a new method that allows the quantitative analysis of four commonly observed microcystin congeners (LR, LA, YR, and RR) and anatoxin-a in a 6-min LC run without solid-phase enrichment. Limits of detection for the microcystin congeners (LR, LA, YR, and RR) and anatoxin-a were <5 ng/L (200-fold lower than the guideline value of 1 μg/L as maximum allowable concentration of MC-LR in drinking water). The method was applied for screening freshwaters in the Pacific Northwest during the bloom and post-bloom periods. The use of high resolution mass spectrometry and concomitant high sensitivity detection of specific fragment ions with high mass accuracy provides an integrated approach for the simultaneous identification and quantification of cyanobacterial toxins. The method is sensitive enough for detecting the toxins in single colonies.