Determination of five positive control drugs in hERG external solution (buffer) by LC-MS/MS to support in vitro hERG assay as recommended by ICH S7B.

ICH S7B recommends screening for hERG channel block using patch clamp recordings to assess a drug's proarrhythmic risk. Block of the hERG channel has been associated with clinical QT prolongation as well as the rare, but potentially fatal ventricular tachyarrhythmia Torsade de Pointes (TdP). During recording, drug concentrations perfused to the cells can deviate from nominal concentrations due to molecule-specific properties (such as non-specific binding), thereby introducing error when assessing drug potency.

hERG block potencies for 5 positive control drugs obtained per ICH E14/S7B Q&As best practices: Impact of recording temperature and drug loss.

According to the ICH S7B guideline, drug candidates are screened for hERG block prior to first-in-human testing to predict the likelihood of delayed repolarization associated with a rare, but life-threatening, ventricular tachyarrhythmia. The new ICH E14 Q&As guideline allows hERG results to be used in later clinical development for decision-making (Q&As 5.1 and 6.

Characterizing the reproducibility in using a liver microphysiological system for assaying drug toxicity, metabolism, and accumulation.

Liver microphysiological systems (MPSs) are promising models for predicting hepatic drug effects. Yet, after a decade since their introduction, MPSs are not routinely used in drug development due to lack of criteria for ensuring reproducibility of results. We characterized the feasibility of a liver MPS to yield reproducible outcomes of experiments assaying drug toxicity, metabolism, and intracellular accumulation.

A Method for Diagnosing Organophosphate Pesticide Exposure in Humans using Liquid Chromatography Coupled Tandem Mass Spectrometry.

Organophosphate (OP) pesticides are commonly utilized worldwide for agricultural purposes and pose a health threat through air, ground, and water contamination. Here, we present a convenient method for diagnosing exposure to OP pesticides in humans. This immunoprecipitation method relies on extraction of butyrylcholinesterase (BChE), a biomarker of OP poisoning that adducts OP compounds, from human serum using agarose beads conjugated to anti-BChE antibodies.

Simultaneous UHPLC-MS/MS method of estradiol metabolites to support the evaluation of Phase-2 metabolic activity of induced pluripotent stem cell derived hepatocytes.

The goal of this study was to develop and validate a high-throughput UHPLC-MS/MS method for simultaneous quantitation of three estradiol metabolites namely estradiol 3-β-D-glucuronide (E3G), estradiol 17-β-D-glucuronide (E17G) and estradiol 3-sulfate (E3S) in cell culture medium to support the characterization of metabolic function of induced pluripotent stem cell (iPSC) derived hepatocytes. To achieve this goal, a simple protein precipitation method was used for sample cleanup. All the metabolites were separated chromatographically using a C-18 column where 10 mM ammonium acetate and acetonitrile was used in gradient flow for 4 min.

Multiplexed ELISA screening assay for nine paralytic shellfish toxins in human plasma.

Paralytic shellfish poisoning is a lethal syndrome that can develop in humans who consume shellfish contaminated with paralytic shellfish toxins. These toxins have a short half-life in the human body, so a rapid diagnostic assessment of the poisoning is necessary. In this paper, we have developed and validated a rapid ELISA screening assay using anti-saxitoxin antibodies to screen nine toxins: saxitoxin; decarbamoyl saxitoxin; gonyautoxin 2,3; decarbamoyl GTX 2,3; neosaxitoxin; and gonyautoxin 1,4, in human plasma with lower limits of detection of 0.

Rapid and Sensitive ELISA Screening Assay for Several Paralytic Shellfish Toxins in Human Urine.

Paralytic shellfish poisoning is caused by a group of paralytic shellfish toxins that are produced by dinoflagellates. Toxins in this group include saxitoxin, neosaxitoxin and gonyautoxins. A rapid diagnostic test to identify poisoning by these toxins can be helpful in guiding the appropriate treatment of victims.

Evaluation of triazole-chelated lanthanides as chemically stabile bioimaging agents.

Europium (Eu), dysprosium (Dy), samarium (Sm), and terbium (Tb) complexes were prepared using the neutral tridentate chelator 2,6-bis(1-benzyl-1,2,3-triazol-4-yl)pyridine and one equivalent of each lanthanide salt. The physicochemical, aerodynamic, and in vitro cellular properties of each lanthanide metal complex were studied to determine their viability as cell surface fluorescent probes. Each compound was characterized by electrospray ionization mass spectroscopy (ESI-MS), ultraperformance liquid chromatography (UPLC), differential scanning calorimetry (DSC), and thermogravimetic analysis (TGA).