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

2021 ◽  
Author(s):  
Dietmar Enko ◽  
Sieglinde Zelzer ◽  
Markus Herrmann ◽  
Robert Krause ◽  
Andreas Meinitzer
Keyword(s):  
Mass Spectrometry ◽  
Column Liquid Chromatography ◽  
Liquid Chromatography ◽  
Tandem Mass Spectrometry ◽  
Therapeutic Drug ◽  
Tandem Mass ◽  
Serum Samples ◽  
Chromatography Tandem Mass Spectrometry ◽  
Liquid Chromatography Tandem Mass ◽  
Dual Column

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.

Development of Sensitive and High-Throughput Liquid Chromatography–Tandem Mass Spectrometry Method for Quantification of Haloperidol in Human Plasma with Phospholipid Removal Pretreatment

2020 ◽  
Author(s):  
Nela Zidekova ◽  
Adam Nemcek ◽  
Martina Sutovska ◽  
Juraj Mokry ◽  
Martin Kertys
Keyword(s):  
Mass Spectrometry ◽  
Liquid Chromatography ◽  
Therapeutic Drug Monitoring ◽  
Tandem Mass Spectrometry ◽  
Human Plasma ◽  
Therapeutic Drug ◽  
Tandem Mass ◽  
Extraction Recovery ◽  
Chromatography Tandem Mass Spectrometry ◽  
Liquid Chromatography Tandem Mass

Abstract Haloperidol, butyrophenone derivative, is a typical antipsychotic drug used in the treatment of schizophrenia, manic phase of bipolar disorder, and acute psychomotor agitations. According to the recent guidelines for therapeutic drug monitoring, it is strongly recommended to measure plasma level during the therapy with haloperidol. The objective of this study was to develop and validate a simple liquid chromatography–tandem mass spectrometry-based method to quantitate haloperidol in human plasma. After one-step extraction procedure using OSTROTM plate, gradient elution on Acquity UPLC BEH C18 (50 × 2.1 mm, 1.7 μm) column over 3.2 min was performed. The detection was conducted on a triple quadrupole tandem mass spectrometer by multiple reaction monitoring mode in positive ionization mode with transitions at m/z 376.29 → 165.14 and m/z 380.28 → 169.17 for haloperidol and haloperidol-d4 (used as an internal standard), respectively. The method was fully validated to cover wide concentration range of 0.05–80 ng/mL in human plasma and meets the criteria for the selectivity, linearity and lower limit of detection, precision and accuracy, matrix effect, extraction recovery, carryover, dilution integrity and stability. The extraction recovery was nearly 100%, and no significant matrix effects were observed. Therefore, the method is applicable to routine therapeutic drug monitoring in patients’ plasma.

scholarly journals Simultaneous Phenotyping and Quantification of α-1-Antitrypsin by Liquid Chromatography–Tandem Mass Spectrometry

2011 ◽  
Vol 57 (8) ◽  
pp. 1161-1168 ◽  
Author(s):  
Yuhong Chen ◽  
Melissa R Snyder ◽  
Yi Zhu ◽  
Linda J Tostrud ◽  
Linda M Benson ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Liquid Chromatography ◽  
Tandem Mass Spectrometry ◽  
Genetic Disorder ◽  
Multiple Reaction Monitoring ◽  
Tandem Mass ◽  
Serum Samples ◽  
Chromatography Tandem Mass Spectrometry ◽  
Liquid Chromatography Tandem Mass ◽  
A1at Deficiency

BACKGROUND α-1-Antitrypsin (A1AT) deficiency results from a genetic disorder at 2 common loci. Diagnosis requires quantification of A1AT and subsequent identification of the specific variant. The current algorithm of laboratory testing for the diagnosis of A1AT deficiency uses a combination of quantification (nephelometry), genotyping, and/or phenotyping. We developed a multiple reaction monitoring liquid chromatography–tandem mass spectrometry (LC-MS/MS) method for simultaneous quantification of A1AT and identification of the 2 most common deficiency alleles present in 95% of the patients with A1AT deficiency. METHODS Serum samples (n = 40) were digested with trypsin, and appropriate 13C/15N-labeled standard peptides were added. We performed LC-MS/MS analysis with a 0.5- by 150-mm C18 column and H2O:acetonitrile:n-propanol:formic acid (A:98:1:1:0.2 and B:10:80:10:0.2; flow 12 μL/min) mobile phase in positive ion mode on a TSQ Quantum triple quadrupole MS system. We measured the A1AT concentration by comparison to a calibration curve and determined the phenotype by the presence or absence of variant peptides. We compared the results to the current phenotyping assay by isoelectric focusing (IEF) and the immunonephelometry quantitative assay. RESULTS For A1AT allele detection, in 39 of 40 samples the LC-MS/MS results were identical to those obtained by IEF gel electrophoresis. The single discrepant result was rerun by IEF at a lower dilution, and the results were in concordance. The A1AT quantification by LC-MS/MS also compared favorably with nephelometry. CONCLUSIONS The LC-MS/MS method correlates well with current phenotyping and nephelometric assays and has the potential to improve the laboratory diagnosis of genetic A1AT deficiency.

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