Comparison of Everolimus QMS Immunoassay on Architect ci4100 and Liquid Chromatography/Mass Spectrometry

Hoffer, Erica; Kurnik, Daniel; Efrati, Edna; Scherb, Inna; Karasik, Marina; Ring, Gil; Bentur, Yedidia

doi:10.1097/ftd.0000000000000126

Cited by 16 publications

(5 citation statements)

References 9 publications

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“…Nevertheless, a previous study had observed a positive bias of 11% of the QMS assay compared to LC-MS/MS 15 . Such a positive bias was confirmed by two more recent studies 16,17 . However, these were single laboratory studies and sample quality and storage conditions were not as rigorously controlled as in the present study.…”

Section: Discussionsupporting

confidence: 61%

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Long-Term Cross-Validation of Everolimus Therapeutic Drug Monitoring Assays

Schniedewind

Niederlechner

Galinkin

et al. 2015

Therapeutic Drug Monitoring

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Background This ongoing academic collaboration was initiated for providing support to set up, validate, and maintain everolimus therapeutic drug monitoring (TDM) assays and to study long-term inter- laboratory performance. Methods This study was based on EDTA whole blood samples collected from transplant patients treated with everolimus in a prospective clinical trial. Samples were handled under controlled conditions during collection, storage, and were shipped on dry ice to minimize freeze-thaw cycles. For more than 1.5 years participating laboratories received a set of 3 blinded samples on a monthly basis. Among others, these samples included individual patient samples, patient sample pools to assess long-term performance and patient samples pools enriched with isolated everolimus metabolites. Results The results between LC-MS/MS and the everolimus Quantitative Microsphere System (QMS, Thermo Fisher) assay were comparable. The monthly inter-laboratory variability (CV%) for cross validation samples ranged from 6.5 – 23.2% (average of 14.8%) for LC-MS/MS and 4.2 – 26.4% (average of 11.1%) for laboratories using the QMS assay. A blinded long-term pool sample was sent to the laboratories for 13 months. The result was 5.31 ± 0.86 ng/mL (range 2.9–7.8 ng/mL) for the LC-MS/MS and 5.20 ± 0.54 ng/mL (range 4.0–6.8 ng/mL) for QMS laboratories. Conclusions Enrichment of patient sample pools with 5–25 ng/mL of purified everolimus metabolites (46-hydroxy everolimus and 39-O-desmethyl everolimus) did not affect the results of either LC-MS/MS or QMS assays. Both LC-MS/MS and QMS assays gave similar results and showed similar performance, albeit with a trend towards higher inter-laboratory variability among laboratories using LC-MS/MS than the QMS assay.

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Section: Discussionsupporting

confidence: 61%

“…However, these were single laboratory studies and sample quality and storage conditions were not as rigorously controlled as in the present study. While the present study was mostly based on samples from kidney transplant patients, these studies 16,17 included a relatively large number of samples from liver and lung transplant patients.…”

Section: Discussionmentioning

confidence: 99%

Long-Term Cross-Validation of Everolimus Therapeutic Drug Monitoring Assays

Schniedewind

Niederlechner

Galinkin

et al. 2015

Therapeutic Drug Monitoring

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“…This can be understood considering the lack of agreement between various IAs despite manufacturers tracing the results to LC-MS/MS (their own reference) as well as between a single IA (QMS/EVER) and several different LC-MS/MS methods. 15,[27][28][29][30][31][32] Therefore, the importance of agreement with LC-MS/MS in evaluating the true direction of bias between IAs should be reconsidered with respect to the characteristics of the "reference" method adopted (eg, using commercially available IVD-CE-labeled or in-house gravimetrically prepared calibrators, extraction with methanol or acetonitrile). 4 Second, this study was designed as a short-term verification study.…”

Section: Discussionmentioning

confidence: 99%

Analytical Performance of the New Siemens Affinity Chrome-Mediated Immunoassay Everolimus Assay and Its Interchangeability With the Thermo Quantitative Microsphere System for Routine Therapeutic Drug Monitoring of Patients After Solid Organ Transplantation

Ialongo

Sapio

Angeloni

2023

Therapeutic Drug Monitoring

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Background: A new homogeneous affinity chrome-mediated immunoassay (ACMIA) "EVRO" from Siemens Healthcare was evaluated for therapeutic drug monitoring of everolimus (EVL) with automated sample pretreatment and compared with quantitative microsphere system (QMS) "EVER" from Thermo Fisher Scientific.Methods: Imprecision, inaccuracy, and limit of quantitation (LoQ) of ACMIA/EVRO were verified using both hemolysate quality control (QC) samples and pooled whole blood specimens. The interchangeability of methods and the agreement of results were analyzed using 72 specimens (from 38, 30, and 4 kidney, liver, and lung transplant recipients, respectively).Results: Within-run imprecision ranged within %CV = 2.81-2.53 with pooled whole blood specimens and within %CV = 2.88-2.53 with QCs; total imprecision with QCs was within %CV = 2.14-1.51. Inaccuracy with value assigned QC was %O = 5.36 at the 5.6 ng/ mL level and %O = 5.56 at the 11.7 ng/mL level. LoQ was 0.93 ng/mL (%CV = 10). Passing-Bablok regression showed a constant bias of 0.679 ng/mL (95% CI: 0.216-1.026) and a proportional bias of 1.326 (95% CI: 1.240-1.425). Bland-Altman analysis showed 5/ 72 (6.9%) paired differences exceeding the limits of agreement and 1/72 (1.4%) paired differences exceeding 1.96 SD to a combined bias of 39.9% after detrending.Conclusions: ACMIA/EVRO shows satisfactory analytical performances that comply with recommendations, but it does not fulfill requirements for interchangeability with QMS/EVER. Particularly, this new assay using sirolimus-specific antibody shows a sizable proportional bias versus the more specific comparator, which may be because of EVL metabolites. This is supported by the lack of agreement for individual differences in most samples collected at the peak concentration (C2). Therefore, further evidence is needed to support the transition of EVL level monitoring from QMS/EVER to ACMIA/EVRO without making extensive changes to both reference interval and patient's baseline.

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“…et al with 169 patient samples, mean everolimus concentration produced by the QMS everolimus test was found to be 31.2% higher than that determined by LC-MS/MS [19]…”

mentioning

confidence: 90%

An Experimental Approach to Risk of Organ Rejection: Demonstration of False Immunosuppressant Results Due to Radiopaque Agents

Gönel¹,

Koyuncu²

2019

Preprint

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Background: Immunosuppressant blood levels should be measured at regular periods in order to keep them within the therapeutic index. Although LC-MS/MS is preferred as a reliable method, some molecules like radiopaque agents in blood matrix may lead to false results. The aim of this study is to investigate the effect of seven different radiopaque agents on immunosuppressant drugs. Methods: Seven different radiopaque agents were added into control materials containing tacrolimus, everolimus, sirolimus and cyclosporine A drugs. Measurements were performed by LC-MS/MS instrument. The amount of deviations from target values were calculated. Results: Immunosuppressant blood levels significantly changed after the administration of radiopaque agents. Seven different radiopaque products led to false negative results in tacrolimus and cyclosporine A levels at a rate of 19.77% to 44.45%. The smallest deviations were seen in everolimus levels with administration of RM6 (gadodiamide) and in sirolimus levels with RM1 (gadobutrol) at rates of 4.04% and 2.11%, respectively. The highest deviations were observed with RM3 (iohexol) administration in everolimus and sirolimus levels at rates of 153.72% and 171.41%, respectively. Conclusions: False immunosuppressant results associated with radiopaque agents may result in organ rejection. Preferring radiopaque agents that cause the least interference risk is important to reduce the organ rejection risk. However, the least risky method is to obtain samples for drug levels before contrast-enhanced imaging.

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Comparison of Everolimus QMS Immunoassay on Architect ci4100 and Liquid Chromatography/Mass Spectrometry

Cited by 16 publications

References 9 publications

Long-Term Cross-Validation of Everolimus Therapeutic Drug Monitoring Assays

Long-Term Cross-Validation of Everolimus Therapeutic Drug Monitoring Assays

Analytical Performance of the New Siemens Affinity Chrome-Mediated Immunoassay Everolimus Assay and Its Interchangeability With the Thermo Quantitative Microsphere System for Routine Therapeutic Drug Monitoring of Patients After Solid Organ Transplantation

An Experimental Approach to Risk of Organ Rejection: Demonstration of False Immunosuppressant Results Due to Radiopaque Agents

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