Development of a novel ion-pairing HPLC-FL method for the separation and quantification of hydroxychloroquine and its metabolites in whole blood.

Hydroxychloroquine (HCQ) is an old antimalarial drug that has proven to be a safe and effective treatment for systemic lupus erythematosus (SLE) and other autoimmune diseases. Since hematic concentration of HCQ is closely related to the therapeutic response, monitoring the levels of the drug and its metabolites in the blood of HCQ-treated patients helps the clinician in the evaluation of partial or complete unresponsiveness to treatment. We developed and validated a novel ion-pairing HPLC-FL method for the simultaneous dosage of HCQ, and its major metabolites desethylhydroxychloroquine, desethylchloroquine and bisdesethylchloroquine, after extraction from whole blood. This methodological approach was used for the analysis of real samples obtained from patients affected by SLE and undergoing HCQ treatment. The same samples were also analyzed using a previously validated LC/MS/MS method and data obtained with the two approaches were in substantial agreement with each other. Results presented in this work indicate that this approach can be successfully used to monitor the level of HCQ and its metabolites in the blood of various categories of patients (i.e. low and high responders, or those not adhering to the therapy). Comparison of HPLC-FL and LC/MS/MS data confirmed the efficacy of the proposed method for routine clinical analyses.

A UHPLC-MS/MS-based method for the simultaneous monitoring of eight antiblastic drugs in plasma and urine of exposed healthcare workers.

Exposure of healthcare workers to anticancer drugs requires the combined action of environmental and biological monitoring to assess the effective level of exposure to these chemicals, to improve awareness and to avoid adverse health effects on this category of workers. Cancer chemotherapeutic drugs show different mechanisms of action due to diverse chemical structures; consequently, they differ in hydrophobicity, pharmacokinetics and pharmacodynamics. Therefore, the appearance, accumulation and elimination of each of these molecules in body fluids and tissues might be extremely variable; this prompts the need for a rapid and versatile analytical protocol for the biological monitoring of possible exposure of workers involved in the manipulation, administration and disposal of cancer chemotherapeutic drugs. In this paper we describe the development, optimization and validation of a UHPLC-MS/MS method for the simultaneous quasi-quantitative analysis of eight widely used antineoplastic drugs, which can be used for the analysis of both urine and blood samples. This methodology was applied to the biological monitoring of healthcare workers exposed to different extents to antiblastic drugs at the University Hospital "San Giovanni di Dio e Ruggi d'Aragona" in Salerno (Italy), and allowed to identify two subjects exposed to irinotecan out of a total of fifteen workers analyzed.

ARResT/Interrogate: an interactive immunoprofiler for IG/TR NGS data.

Motivation: The study of immunoglobulins and T cell receptors using next-generation sequencing has finally allowed exploring immune repertoires and responses in their immense variability and complexity. Unsurprisingly, their analysis and interpretation is a highly convoluted task. Results: We thus implemented ARResT/Interrogate, a web-based, interactive application. It can organize and filter large amounts of immunogenetic data by numerous criteria, calculate several relevant statistics, and present results in the form of multiple interconnected visualizations. Availability and Implementation: ARResT/Interrogate is implemented primarily in R, and is freely available at http://bat.infspire.org/arrest/interrogate/ Contact: nikos.darzentas@gmail.com Supplementary Information: Supplementary data are available at Bioinformatics online.