Immunosuppressive drugs in whole blood: validation of a commercially available liquid chromatography/tandem mass spectrometry kit and comparison with immunochemical assays

Polledri, Elisa; Mercadante, Rosa; Fusarini, Chiara Ferraris; Maiavacca, Rita; Fustinoni, Silvia

doi:10.1002/rcm.7887

Cited by 19 publications

(8 citation statements)

References 18 publications

(24 reference statements)

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“…Tacrolimus whole-blood concentrations and safety parameters were measured in the accredited central laboratory of Heidelberg University Hospital. For tacrolimus, the commercial assay MassTox Immunosuppressants in Whole Blood OneMinute Test was used, 10,11 which was validated according to the manufacturer's instructions using the 6PLUS1 Multilevel Calibrator Set Immunosuppressants (Chromsystems Instruments & Chemicals GmbH, Gräfelfing, Germany). Samples were analyzed using ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS; Waters ACQUITY TQD, Eschborn, Germany).…”

Section: Analytical Assaysmentioning

confidence: 99%

Differential Effect of a Continental Breakfast on Tacrolimus Formulations With Different Release Characteristics

Huppertz

Bollmann

Behnisch

et al. 2021

Clinical Pharm in Drug Dev

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Food reduces tacrolimus bioavailability after immediate-release tacrolimus (IR-Tac) and after a new prolonged-release tacrolimus formulation (PR-Tac), when using a high-fat breakfast, but the effects of a continental breakfast on PR-Tac are unknown. In an open-label, 4-phase, randomized, 2-sequence, crossover pharmacokinetic trial, 36 healthy volunteers (18 females) received single 5-mg tacrolimus doses as PR-Tac and as IR-Tac fasted or with a standardized continental breakfast. Tacrolimus pharmacokinetics were analyzed using noncompartmental methods and mixed-model analysis of variance.The continental breakfast significantly decreased average tacrolimus exposure (area under the plasma concentration-time curve) with both preparations (IR-Tac, 67%; 90% confidence interval [CI], 59%-75%; P < .01; and PR-Tac, 79%; 90%CI, 70%-89%; P < .01) with a nonsignificant difference between both preparations (P = .10). The maximum concentration (C max ) and the time to maximum concentration (t max ) were significantly affected only after IR-Tac (C max IR-Tac, 39%; 90%CI, 34%-45%; P < .01; and PR-Tac, 87%; 90%CI, 76%-101%; P = .11; t max IR-Tac, 212%, 90%CI, 179%-252%; P < .01; and PR-Tac, 101%; 90%CI, 86%-120%; P = .89), which was significantly different between both preparations (P < .01). Considering switching from IR-Tac to PR-Tac, predicted dose requirements differed according to the timing of drug intake in relation to food. In conclusion, a continental breakfast decreased average tacrolimus exposure of both preparations to a similar extent. C max and t max were affected only after IR-Tac. The effect of a standardized continental breakfast on PR-Tac was considerably smaller than previously reported effects of a high-fat breakfast on PR-Tac.

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Section: Analytical Assaysmentioning

confidence: 99%

Differential Effect of a Continental Breakfast on Tacrolimus Formulations With Different Release Characteristics

Huppertz

Bollmann

Behnisch

et al. 2021

Clinical Pharm in Drug Dev

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“…to LC-MS/MS-based methods, and these differences have been mostly attributed to the crossreactivity of ISD metabolites. Proportional differences are especially observed for SIR, but it also must be kept in mind that proportional and systematic differences depend on the type of commercial immunoassay kit and external calibrator reference materials used [8,9,42,43].…”

Section: Several Studies Have Shown the Positive Bias Of Immunoassay-...mentioning

confidence: 99%

Rapid determination of tacrolimus and sirolimus in whole human blood by direct coupling of solid-phase microextraction to mass spectrometry via microfluidic open interface

Nazdrajić

Tascón

Rickert

et al. 2021

Analytica Chimica Acta

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“…However, in recent years, new immunoassay methods have ameliorated some of these problems [ 4 , 5 ]. In contrast, LC-MS/MS is considered a worldwide gold standard method for TDM because of its high sensitivity, high specificity, and suitability for multiplexing including metabolites [ 6 – 8 ]. Nevertheless, it has disadvantages such as unsuitability for direct injection, limited automation, time-consuming procedure, the need for manual deproteination of samples, and the requirement of special training for users.…”

Section: Introductionmentioning

confidence: 99%

Validation of an automated sample preparation module directly connected to LC-MS/MS (CLAM-LC-MS/MS system) and comparison with conventional immunoassays for quantitation of tacrolimus and cyclosporin A in a clinical setting

Shimada,

Kawakami,

Fujita

et al. 2024

J Pharm Health Care Sci

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Background Therapeutic drug monitoring (TDM) systems generally use either liquid chromatography/tandem mass spectrometry (LC-MS/MS) or immunoassay, though both methodologies have disadvantages. In this study, we aimed to evaluate whether a CLAM-LC-MS/MS system, which consists of a sample preparation module directly connected to LC-MS/MS, could be used for clinical TDM work for immunosuppressive drugs in whole blood, which requires a hemolytic process. For this purpose, we prospectively validated this system for clinical measurement of tacrolimus and cyclosporin A in patients’ whole blood. The results were also compared with those of commercial immunoassays. Methods Whole blood from patients treated with tacrolimus or cyclosporin A at the Department of Nephrology and Departments of Rheumatology, Kanazawa University Hospital, from May 2018 to July 2019 was collected with informed consent, and drug concentrations were measured by CLAM-LC-MS/MS and by chemiluminescence immunoassay (CLIA) for tacrolimus and affinity column-mediated immunoassay (ACMIA) for cyclosporin A. Correlations between the CLAM-LC-MS/MS and immunoassay results were analyzed. Results Two hundred and twenty-four blood samples from 80 patients were used for tacrolimus measurement, and 76 samples from 21 patients were used for cyclosporin A. Intra- and inter-assay precision values of quality controls were less than 7%. There were significant correlations between CLAM-LC-MS/MS and the immunoassays for tacrolimus and cyclosporin A (Spearman rank correlation coefficients: 0.861, 0.941, P < 0.00001 in each case). The drug concentrations measured by CLAM-LC-MS/MS were about 20% lower than those obtained using the immunoassays. CLAM-LC-MS/MS maintenance requirements did not interfere with clinical operations. Compared to manual pretreatment, automated pretreatment by CLAM showed lower inter-assay precision values and greatly reduced the pretreatment time. Conclusions The results obtained by CLAM-LC-MS/MS were highly correlated with those of commercial immunoassay methods. CLAM-LC-MS/MS offers advantages in clinical TDM practice, including simple, automatic pretreatment, low maintenance requirement, and avoidance of interference.

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Immunosuppressive drugs in whole blood: validation of a commercially available liquid chromatography/tandem mass spectrometry kit and comparison with immunochemical assays

Cited by 19 publications

References 18 publications

Differential Effect of a Continental Breakfast on Tacrolimus Formulations With Different Release Characteristics

Differential Effect of a Continental Breakfast on Tacrolimus Formulations With Different Release Characteristics

Rapid determination of tacrolimus and sirolimus in whole human blood by direct coupling of solid-phase microextraction to mass spectrometry via microfluidic open interface

Validation of an automated sample preparation module directly connected to LC-MS/MS (CLAM-LC-MS/MS system) and comparison with conventional immunoassays for quantitation of tacrolimus and cyclosporin A in a clinical setting

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