Falsely high sirolimus concentrations due to everolimus cross-reactivity in the Siemens sirolimus immunoassay: Corrective actions implemented

Bowen, Raffick A.R.; Rieta, Ranilo; Joshi, Rohan P.; Lee, Roy C.

doi:10.1016/j.cca.2017.10.025

Cited by 3 publications

(1 citation statement)

References 4 publications

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“…In this respect, QMS/EVER samples show a large positive d%, with a marked upward trend from low to high, which may represent the concentration-dependent crossreactivity of the assay. 19 Likewise, QCs supplied with ACMIA/EVRO show positive %d, which confirms, to some degree, the correction applied to the calibration, although it was greater than expected based on Figure 3A.…”

Section: Discussionsupporting

confidence: 69%

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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Section: Discussionsupporting

confidence: 69%

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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Development of a precise quantitative method for monitoring sirolimus in whole blood using LC/ESI–MS/MS

Shigeta

Kikuchi

Tanaka

et al. 2020

Biomedical Chromatography

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Sirolimus is used on patients after solid organ transplantation and on lymphangioleiomyomatosis (LAM) patients, and therapeutic drug monitoring is required in clinical practice. We have previously reported an accurate method for quantitative determination of sirolimus, but its sample preparation step was complicated. In this study, we developed a modified liquid chromatography/electrospray ionization tandem mass spectrometry (LC/ESI–MS/MS) method for sirolimus quantification. A supported liquid extraction cartridge was used to purify sirolimus from whole blood and ion suppression was mostly prevented. The validation results met the acceptance criteria. This method was compared with the antigen conjugated magnetic immunoassay (ACMIA) and our previously reported method, using whole blood samples from LAM patients. Comparison of the Bland–Altman plots of the currently developed method and the previous method revealed no significant difference between the two methods (mean bias, −2.02%; 95% CI, −7.81–3.78). The values obtained using ACMIA were significantly higher than those obtained using the current method by 13.87% (95% CI, 6.49–21.25) owing to cross‐reactivity. The degrees of cross reactivities in LAM patients and in organ transplant patients were similar, and our LC/ESI–MS/MS method precisely measured the blood concentrations of sirolimus.

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Everolimus/sirolimus

2019

Reactions Weekly

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Falsely high sirolimus concentrations due to everolimus cross-reactivity in the Siemens sirolimus immunoassay: Corrective actions implemented

Cited by 3 publications

References 4 publications

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

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

Development of a precise quantitative method for monitoring sirolimus in whole blood using LC/ESI–MS/MS

Everolimus/sirolimus

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