An isotope dilution LC-MS/MS based candidate reference method for the quantification of cyclosporine A, tacrolimus, sirolimus and everolimus in human whole blood

Taibon, Judith; Rooij, Milou van; Schmid, Rupert; Singh, Neeraj; Albrecht, Eva; Wright, Jo Anne; Geletneky, Christian; Schuster, Carina; Mörlein, Sophie; Vogeser, Michael; Seger, Christoph; Pongratz, Stephan; Kobold, Uwe

doi:10.1016/j.clinbiochem.2019.11.006

Cited by 21 publications

(6 citation statements)

References 24 publications

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“…Furthermore, the possibility of metrological traceability has increased with the development of standard reference materials for some ISDs 12 and the publication of reference measurement procedures. 13,14 As the need for further standardization is still present, progress is being driven by the IFCC Working Group for immunosuppressive drugs.…”

Section: Introductionmentioning

confidence: 99%

Immunosuppressant Monitoring—Performance of the First Mass Spectrometry–Based Automated Clinical Analyzer Cascadion

Grote-Koska

Czajkowski

Antje

et al. 2023

Therapeutic Drug Monitoring

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Background: Automatic analyzers simplify processes and may help improve standardization. The first automated analyzer based on mass spectrometry is available and offers a panel for monitoring cyclosporin A, tacrolimus, sirolimus, and everolimus. Method comparisons and evaluation tests are presented to verify the capability of the Cascadion system for use in a clinical laboratory.Methods: Sample preparation and measurements were performed using the Cascadion clinical analyzer. More than 1000 measurement values of patient samples were compared with an in vitro diagnosticcertified assay run on a liquid chromatography tandem mass spectrometry instrument. Precision and accuracy were determined using commercial quality control and external quality assessment (EQA) samples.Results: A good correlation between the 2 instruments was observed (Pearson correlation r = 0.956-0.996). Deming regression revealed 95% confidence intervals of slopes and intercepts covering the values 1 and 0, for sirolimus and everolimus, respectively, indicating equivalence of both measuring systems. However, for cyclosporin A, a bias was observed and confirmed using a Bland-Altman plot (29.1%). Measurement repeatability and intermediate measurement precision were appropriate showing coefficients of variation of 0.9%-6.1% and 2.0%-5.3%, respectively. Accuracy according to internal quality controls was 85%-111% and 81%-100% in the EQA samples of Reference Institute of Bioanalytics and Laboratory of the Government Chemist, respectively. High robustness was found with regard to the linearity of the calibration lines (linear regression coefficient r 2 . 0.99). Carryover was negligible (0.1%). Conclusions:The Cascadion automatic analyzer produced convincing results in the measurement of patient, control, and EQA samples. The throughput was sufficient for routine use. Overall, it can be used as an alternative to open liquid chromatography tandem mass spectrometry instruments for immunosuppressant monitoring, simplifying processes without the need for specially trained personnel.

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Section: Introductionmentioning

confidence: 99%

Immunosuppressant Monitoring—Performance of the First Mass Spectrometry–Based Automated Clinical Analyzer Cascadion

Grote-Koska

Czajkowski

Antje

et al. 2023

Therapeutic Drug Monitoring

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“…Numerous sole or simultaneous methods for measuring blood EVR concentration using HPLC-MS/MS or UHPLC-MS/MS have been developed to date. [9][10][11][12][13][18][19][20][21][22][23][24][25][26][27][28][29][30][31] To the best of our knowledge, the method developed by Rickert et al 21 has the widest calibration curve range, but the quotient of the upper and lower limits is 400, which is narrower than that of our method (500). Furthermore, among the methods reported, those of Rickert et al 21 and Taibon et al 22 have the lowest limit of calibration range of 0.25 ng/mL, which is higher than that of our method (0.1 ng/mL).…”

Section: Discussionmentioning

confidence: 84%

“…[9][10][11][12][13][18][19][20][21][22][23][24][25][26][27][28][29][30][31] To the best of our knowledge, the method developed by Rickert et al 21 has the widest calibration curve range, but the quotient of the upper and lower limits is 400, which is narrower than that of our method (500). Furthermore, among the methods reported, those of Rickert et al 21 and Taibon et al 22 have the lowest limit of calibration range of 0.25 ng/mL, which is higher than that of our method (0.1 ng/mL). All other reported methods have a lower limit of calibration range of 0.5 ng/mL or higher and hence are not suitable to measure the EVR concentration of 1 patient (0.4 ng/mL) as determined in our study.…”

Section: Discussionmentioning

confidence: 84%

“…Nevertheless, this matrix also increases the stress on the analytical column and mass spectrometer. Some reports have used a conventional solid-phase extraction method, 9,22 which requires many time-consuming procedures, such as conditioning, equilibration, washing, and elution. Semiautomatic solid-phase extraction and online solid-phase extraction automatically perform complex operations to increase the efficiency of the work processes.…”

Section: Discussionmentioning

confidence: 99%

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High-Sensitivity and High-Throughput Quantification of Everolimus in Human Whole Blood Using Ultrahigh-Performance Liquid Chromatography Coupled With Tandem Mass Spectrometry

Miyagi

Tanaka

Hirata

et al. 2022

Therapeutic Drug Monitoring

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Background: Rigorous dose adjustment by therapeutic drug monitoring (TDM) is recommended when everolimus (EVR) is administered for immunosuppression. In this study, the authors developed a highly sensitive ultrahigh-performance liquid chromatography coupled with the tandem mass spectrometry (UHPLC-MS/ MS) method for measuring EVR concentrations in whole blood using a high-throughput solid-phase extraction method for sample pretreatment. Furthermore, the blood EVR concentrations in routine TDM samples from patients who underwent renal transplantation measured using the established UHPLC-MS/MS method were compared with those measured using the latex agglutination turbidimetric immunoassay (LTIA).Methods: Blood samples were pretreated by solid-phase extraction using a 96-well HLB mElution plate. The clinical application of the newly developed method was evaluated using 87 blood samples from 19 patients who underwent kidney transplant. Results:The calibration curve showed good linearity over a wide range of 0.1-50 ng/mL, with relative error #15% obtained from the back calculation of calibrators, and #20% for the lower limit of quantification. Within-batch and batch-to-batch accuracies and precisions fulfilled the acceptance criteria of the US Food and Drug Administration guidelines for bioanalytical method validation. The extraction recovery rates were good ($65.2%), and almost no matrix effects were found in any of the quality control samples. Blood EVR concentrations measured by UHPLC-MS/MS were positively correlated with those measured by LTIA. A Bland-Altman plot indicated that the UHPLC-MS/MS method yielded better measurements than the LTIA method, regardless of the concentration.Conclusions: Therefore, the authors succeeded in developing a novel high-sensitivity and high-throughput method for measuring blood EVR concentration by UHPLC-MS/MS using a mElution plate for sample pretreatment.

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“…where A R-labeled and A R-unlabeled are the MS peak areas after derivatization with a labeled and unlabeled reagent, respectively; C si and C R are the metabolite's concentrations in the test sample and reference sample, respectively; A si and A Ri-labed are the metabolite's peak areas in the unlabeled test sample and the labeled reference sample, respectively. A qNMR-guided LC-MS/MS study was able to determine the absolute quantification of four immunosuppressive drugs in human whole blood [134]. The four drugs, cyclosporine A, tacrolimus, sirolimus, and everolimus, were detected over a concentration range of 0.25 to 50 ng/mL with an overall uncertainty of ≤9.0%.…”

Section: Multiplatform Approach To 1d Metabolite Quantificationmentioning

confidence: 99%

Quantitative NMR-Based Biomedical Metabolomics: Current Status and Applications

2020

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Nuclear Magnetic Resonance (NMR) spectroscopy is a quantitative analytical tool commonly utilized for metabolomics analysis. Quantitative NMR (qNMR) is a field of NMR spectroscopy dedicated to the measurement of analytes through signal intensity and its linear relationship with analyte concentration. Metabolomics-based NMR exploits this quantitative relationship to identify and measure biomarkers within complex biological samples such as serum, plasma, and urine. In this review of quantitative NMR-based metabolomics, the advancements and limitations of current techniques for metabolite quantification will be evaluated as well as the applications of qNMR in biomedical metabolomics. While qNMR is limited by sensitivity and dynamic range, the simple method development, minimal sample derivatization, and the simultaneous qualitative and quantitative information provide a unique landscape for biomedical metabolomics, which is not available to other techniques. Furthermore, the non-destructive nature of NMR-based metabolomics allows for multidimensional analysis of biomarkers that facilitates unambiguous assignment and quantification of metabolites in complex biofluids.

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An isotope dilution LC-MS/MS based candidate reference method for the quantification of cyclosporine A, tacrolimus, sirolimus and everolimus in human whole blood

Cited by 21 publications

References 24 publications

Immunosuppressant Monitoring—Performance of the First Mass Spectrometry–Based Automated Clinical Analyzer Cascadion

Immunosuppressant Monitoring—Performance of the First Mass Spectrometry–Based Automated Clinical Analyzer Cascadion

High-Sensitivity and High-Throughput Quantification of Everolimus in Human Whole Blood Using Ultrahigh-Performance Liquid Chromatography Coupled With Tandem Mass Spectrometry

Quantitative NMR-Based Biomedical Metabolomics: Current Status and Applications

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