Successful and cost-efficient replacement of immunoassays by tandem mass spectrometry for the quantification of immunosuppressants in the clinical laboratory

Hétu, Pierre-Olivier; Robitaille, Robert; Vinet, Bernard

doi:10.1016/j.jchromb.2011.10.034

Cited by 26 publications

(16 citation statements)

References 41 publications

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“…C min could have been at 0 h post-dose (C 0 ) or at 12 h post-dose (C 12 ) (with twice-daily dosing), or at 24 h post-dose (C 24 ) (with once-daily dosing). Various assays were used for tacrolimus drug measurement, with many studies using the optimal, specific and sensitive liquid chromatography-tandem mass spectrometry (LC-MS/MS) techniques, but a significant number of studies used the relatively less specific but technologically simpler immunoassays [71,72]. Thus, actual reported concentrations and exposures measured using these immunoassays would appear higher than those from studies using LC-MS/MS assays.…”

Section: Pharmacokineticsmentioning

confidence: 99%

Clinical Pharmacokinetics of Once-Daily Tacrolimus in Solid-Organ Transplant Patients

Staatz

Tett

2015

Clin Pharmacokinet

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Tacrolimus is a pivotal immunosuppressant agent used in solid-organ transplantation. It was originally formulated for oral administration as Prograf(®), a twice-daily immediate-release capsule. In an attempt to improve patient adherence, retain manufacturer market share and/or reduce health care costs, newer once-daily prolonged-release formulations of tacrolimus (Advagraf(®) and Envarsus(®) XR) and various generic versions of Prograf(®) are becoming available. Tacrolimus has a narrow therapeutic index. Small variations in drug exposure due to formulation differences can have a significant impact on patient outcomes. The aim of this review is to critically analyse the published data on the clinical pharmacokinetics of once-daily tacrolimus in solid-organ transplant patients. Forty-three traditional (non-compartmental) and five population pharmacokinetic studies were identified and evaluated. On the basis of the stricter criteria for narrow-therapeutic-index drugs, Prograf(®), Advagraf(®) and Envarsus(®) XR are not bioequivalent [in terms of the area under the concentration-time curve from 0 to 24 h (AUC0-24) or the minimum concentration (C min)]. Patients may require a daily dosage increase if converted from Prograf(®) to Advagraf(®), while a daily dosage reduction appears necessary for conversion from Prograf(®) to Envarsus(®) XR. Prograf(®) itself, or generic immediate-release tacrolimus, can be administered in a once-daily regimen with a lower than double daily dose being reported to give 24-h exposure equivalent to that of a twice-daily regimen. Intense clinical and concentration monitoring is prudent in the first few months after any conversion to once-daily tacrolimus dosing; however, there is no guarantee that therapeutic drug monitoring strategies applicable to one formulation (or twice-daily dosing) will be equally applicable to another. The correlation between the tacrolimus AUC0-24 and C min is variable and not strong for all three formulations, indicating that trough measurements may not always give a good indication of overall drug exposure. Further investigation is required into whether the prolonged-release formulations have reduced within-subject pharmacokinetic variability, which would be a distinct advantage. Whether the effects of factors that influence tacrolimus absorption and pre-systemic metabolism (patient genotype status; gastrointestinal disease and disorders) and drug interactions differ across the formulations needs to be further elucidated. Most pharmacokinetic comparison studies to date have involved relatively stable patients, and many have been sponsored by the pharmaceutical companies manufacturing the new formulations. Larger randomized, controlled trials are needed in different transplant populations to determine whether there are differences in efficacy and toxicity across the formulations and whether formulation conversion is worthwhile in the longer term. While it has been suggested that once-daily administration of tacrolimus may improve patient compliance, further studies a...

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Section: Pharmacokineticsmentioning

confidence: 99%

Clinical Pharmacokinetics of Once-Daily Tacrolimus in Solid-Organ Transplant Patients

Staatz

Tett

2015

Clin Pharmacokinet

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“…When clearance is impaired, leading to buildup of drug metabolites, such cross-reactivity can result in a significant over-estimation of the tacrolimus concentration. Additionally, the cost-per-test for immunoassay is higher than for mass spectrometry (MS) assays (4,5). Many of the tacrolimus immunoassays still require manual sample pretreatment before automated analysis by the instrument, while only a selective few may include on-board hemolysis of whole blood specimens to be truly automated.…”

Section: Introductionmentioning

confidence: 99%

Rapid measurement of tacrolimus in whole blood by paper spray-tandem mass spectrometry (PS-MS/MS)

Shi

Gierari

Manicke

et al. 2015

Clinica Chimica Acta

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“…Therapeutic drug monitoring is integral to the standard of care for a growing number of clinical disciplines, including solid organ transplantation (1), oncology (2, 3), infectious disease management (4 – 6), and psychiatry (7). Although these tests provide valuable information that improves patient care by facilitating the maximization of the therapeutic effect and minimization of untoward side effects, the laboratory costs involved in performing these tests— either by MS or immunoassay—are not trivial (8, 9). …”

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confidence: 99%

Alternative Calibration Strategies for the Clinical Laboratory: Application to Nortriptyline Therapeutic Drug Monitoring

et al. 2013

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BACKGROUND The addition of a calibration curve with every run is both time-consuming and expensive for clinical mass spectrometry assays. We present alternative calibration strategies that eliminate the need for a calibration curve except as required by laboratory regulations. METHODS We measured serum nortriptyline concentrations prospectively in 68 patients on 16 days over a 2-month period using a method employing calibration schemes that relied on the measurement of the response ratio (RR) corrected by the response factor (RF), i.e., a measurement of the RR for an equimolar mixture of the analyte and internal standard. Measurements were taken with contemporaneous RF (cRF) measurements as well as sporadic RF (sRF) measurements. The measurements with these alternative calibration schemes were compared against the clinical results obtained by interpolation on a calibration curve, and those differences were evaluated for analytical and clinical significance. RESULTS The differences between the values measured by cRF and sRF calibration and interpolation on a calibration curve were not significant (P = 0.088 and P = 0.091, respectively). Both the cRF-and sRF-based calibration results demonstrated a low mean bias against the calibration curve interpolations of 3.69% (95% CI, −15.8% to 23.2%) and 3.11% (95% CI, −16.4% to 22.6%), respectively. When these results were classified as subtherapeutic, therapeutic, or supratherapeutic, there was categorical agreement in 95.6% of the cRF calibration results and 94.1% of the sRF results. CONCLUSIONS cRF and sRF calibration in a clinically validated liquid chromatography–tandem mass spectrometry assay yields results that are analytically and clinically commensurate to those produced by interpolation with a calibration curve.

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Successful and cost-efficient replacement of immunoassays by tandem mass spectrometry for the quantification of immunosuppressants in the clinical laboratory

Cited by 26 publications

References 41 publications

Clinical Pharmacokinetics of Once-Daily Tacrolimus in Solid-Organ Transplant Patients

Clinical Pharmacokinetics of Once-Daily Tacrolimus in Solid-Organ Transplant Patients

Rapid measurement of tacrolimus in whole blood by paper spray-tandem mass spectrometry (PS-MS/MS)

Alternative Calibration Strategies for the Clinical Laboratory: Application to Nortriptyline Therapeutic Drug Monitoring

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