scholarly journals Development, Validation, and Comparison of Two Mass Spectrometry Methods (LC-MS/HRMS and LC-MS/MS) for the Quantification of Rituximab in Human Plasma

Molecules ◽  
2021 ◽  
Vol 26 (5) ◽  
pp. 1383
Author(s):  
Aurélien Millet ◽  
Nihel Khoudour ◽  
Dorothée Lebert ◽  
Christelle Machon ◽  
Benjamin Terrier ◽  
...  

Rituximab is a chimeric immunoglobulin G1-kappa (IgG1κ) antibody targeting the CD20 antigen on B-lymphocytes. Its applications are various, such as for the treatment of chronic lymphoid leukemia or non-Hodgkin’s lymphoma in oncology, and it can also be used in the treatment of certain autoimmune diseases. Several studies support the interest in therapeutic drug monitoring to optimize dosing regimens of rituximab. Thus, two different laboratories have developed accurate and reproductive methods to quantify rituximab in human plasma: one using liquid chromatography quadripolar tandem mass spectrometer (LC-MS/MS) and the other, liquid chromatography orbitrap tandem mass spectrometer (LC-MS/HRMS). For both assays, quantification was based on albumin depletion or IgG-immunocapture, surrogate peptide analysis, and full-length stable isotope-labeled rituximab. With LC-MS/MS, the concentration range was from 5 to 500 µg/mL, the within- and between-run precisions were <8.5%, and the limit of quantitation was 5 µg/mL. With LC-MS/HRMS, the concentration range was from 10 to 200 µg/mL, the within- and between-run accuracy were <11.5%, and the limit of quantitation was 2 µg/mL. Rituximab plasma concentrations from 63 patients treated for vasculitis were compared. Bland–Altman analysis and Passing–Bablok regression showed the interchangeability between these two methods. Overall, these methods were robust and reliable and could be applied to routine clinical samples.

2005 ◽  
Vol 88 (4) ◽  
pp. 1114-1117 ◽  
Author(s):  
Hiroaki Kaji ◽  
Takayoshi Maiguma ◽  
Yoko Inukai ◽  
Hiroshige Ono ◽  
Ritsuko Taniguchi ◽  
...  

Abstract A simple liquid chromatography (LC) method was developed for determination of the therapeutic level of mizoribine in human plasma. After precipitation of plasma proteins with 6% perchloric acid, mizoribine was determined by LC with spectophotometric detection. The peak height for mizoribine was linearly related to its concentrations, which ranged from 0.09 to 3.13 μg/mL. Therefore, the limit of quantitation was considered to be 0.09 μg/mL. The accuracy was 104.96–107.37%. The intra- and interday relative standard deviation values were in the range of 1.10–3.25%. The detection limit was 0.025 μ g/mL, defined as a signal-to-noise ratio of 3. The plasma concentrations of mioribine were not related to the dosage. Because mizoribine was mainly excreted in the urine, the plasma concentrations of mizoribine might be affected by a change in renal function. Therefore, the mizoribine concentration in blood should be monitored and the dosage adjusted, depending on the condition of renal function. It was suggested that the present method may be applied well in the therapeutic drug monitoring for mizoribine.


Author(s):  
Nela Zidekova ◽  
Adam Nemcek ◽  
Martina Sutovska ◽  
Juraj Mokry ◽  
Martin Kertys

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.


2018 ◽  
Vol 62 (11) ◽  
Author(s):  
Carsten Müller ◽  
Cornelia Fietz ◽  
Philipp Koehler ◽  
Graham Sibley ◽  
Achu Che Awah Nforbugwe ◽  
...  

ABSTRACT A fast and easy-to-use liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for the determination and quantification of a novel antifungal drug, olorofim (F901318), a member of the novel class of orotomides, in human plasma and serum was developed and validated. Sample preparation was based on protein precipitation with acetonitrile and subsequent centrifugation. An isotope-labeled analogue of F901318 was employed as an internal standard. Chromatographic separation was achieved using a 50-mm by 2.1-mm, 1.9-μm, polar Hypersil Gold C18 column and isocratic mobile phase consisting of 0.1% formic acid–acetonitrile (60%-40%, vol/vol) at a flow rate of 330 μl/min. The analyte was detected using a triple-stage quadrupole mass spectrometer operated in selected reaction monitoring (SRM) mode with positive heated electrospray ionization (HESI+) within a single runtime of 2.00 min. The present LC-MS/MS method was validated according to the international guidelines of the International Conference on Harmonisation (ICH) and the U.S. Food and Drug Administration (FDA). Linearity of F901318 concentration ranges was verified by the Mandel test. The calibration curve was tested linear across the range and fitted using least-squares regression with a weighting factor of the reciprocal concentration. The limit of detection was 0.0011 mg/liter, and the lower limit of quantitation was 0.0033 mg/liter. Intraday and interday precisions ranged from 1.17% to 3.23% for F901318, and intraday and interday accuracies (percent bias) ranged from 0.75% to 5.01%. In conclusion, a method was established for the rapid quantitation of F901318 concentrations in serum and plasma samples in patient trials, and it optimizes therapeutic drug monitoring in applying an easy-to-use single method.


Molecules ◽  
2020 ◽  
Vol 25 (8) ◽  
pp. 1763
Author(s):  
Junhee Kim ◽  
Hyun-Deok Cho ◽  
Joon Hyuk Suh ◽  
Ji-Youn Lee ◽  
Eunyoung Lee ◽  
...  

Many studies have analyzed nicotine metabolites in blood and urine to determine the toxicity caused by smoking, and assess exposure to cigarettes. Recently, hair and nails have been used as alternative samples for the evaluation of smoking, as not only do they reflect long-term exposure but they are also stable and easy to collect. Liquid-liquid or solid-phase extraction has mainly been used to detect nicotine metabolites in biological samples; however, these have disadvantages, such as the use of toxic organic solvents and complex pretreatments. In this study, a modified QuEChERS method was proposed for the first time to prepare samples for the detection of nicotine metabolite cotinine (COT) and trans-3′-hydroxycotinine (3-HCOT) in hair and nails. High-performance liquid chromatography–tandem mass spectrometry (LC–MS/MS) was used to analyze traces of nicotine metabolites. The established method was validated for selectivity, linearity, lower limit of quantitation, accuracy, precision and recovery. In comparison with conventional liquid-liquid extraction (LLE), the proposed method was more robust, and resulted in higher recoveries with favorable analytical sensitivity. Using this method, clinical samples from 26 Korean infants were successfully analyzed. This method is expected to be applicable in the routine analysis of nicotine metabolites for environmental and biological exposure monitoring.


2015 ◽  
Vol 7 (19) ◽  
pp. 8048-8059 ◽  
Author(s):  
Yong-Lai Feng ◽  
Xiangjun Liao ◽  
Genevieve Grenier ◽  
Nathalie Nguyen ◽  
Peter Chan

Phthalates are a group of chemicals used in a variety of products worldwide.


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