Implementation of a Dual-Column Liquid Chromatography-Tandem Mass-Spectrometry Method for the Quantification of Isavuconazole in Clinical Practice

Abstract

Objectives Therapeutic drug monitoring (TDM) of isavuconazole, which is a novel broad-spectrum antimycoticum against invasive fungal infections, ensures an effective exposure of the drug and minimizes the risk of toxicity. This study is aimed at evaluating the analytical performance of a dual-column liquid chromatography-tandem mass-spectrometry (LC-MS/MS) method for isavuconazole quantification. Materials and Methods The method was performed on a Voyager TSQ Quantum triple quadrupole instrument equipped with an Ultimate 3000 chromatography system (Thermo Fisher Scientific, San Jose, California, United States). Analytical and preanalytical requirements of the isavuconazole LC-MS/MS method were evaluated. Sample stability measurements were performed at room temperature (RT) and in serum tubes with separator gel. Results The isavuconazole LC-MS/MS method was linear over the concentration range of 0.2 to 12.8 mg/L. The coefficient of determination (r 2) always exceeded 0.999. Within- and between-run precision ranged between 1.4 to 2.9% and 1.5 to 3.0%, the recovery between 93.9 and 102.7%. At RT, serum samples were stable for 3 days. Isavuconazole serum concentrations were significantly lower after incubation (18 hours) in serum tubes with separator gel at RT. Conclusion The dual-column isavuconazole LC-MS/MS is a reliable tool for the TDM of isavuconazole. Serum samples are stable for at least 3 days and should be collected in tubes without separator gel.

A protocol for an international, multicentre pharmacokinetic study for Screening Antifungal Exposure in Intensive Care Units: The SAFE-ICU study

“…Immediately after collection, blood samples will be placed on ice and centrifuged within 6 h of collection to separate the plasma, which will be transferred to a labelled vial for frozen storage (at −20 °C for short-term storage or −80 °C for longer storage) [11] , [12] , [13] until distribution to the bioanalytical laboratory.…”

“…Sampling times will be scheduled 2 h after the new bags are attached, and the volume of abdominal fluid accumulated in the 2-h sample collection will be recorded. Samples will be collected into a labelled vial and will be placed on ice immediately after collection before being transferred for frozen storage (at −20 °C for short-term storage or −80 °C for longer storage) [11] , [12] , [13] until distribution to the bioanalytical laboratory.…”

Isavuconazole plasma concentrations in critically ill patients during extracorporeal membrane oxygenation

“… 11 , 20 Internal quality controls were routinely included in each test run and international robin round tests are performed in the laboratory. 21 …”