Impact of Interferences Including Metabolite Crossreactivity on Therapeutic Drug Monitoring Results

Dasgupta, Amitava

doi:10.1097/ftd.0b013e318261c2c9

Cited by 24 publications

(7 citation statements)

References 76 publications

(53 reference statements)

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“…Well characterized interferents include hyperlipidemia, hyperbilirubinemia and metabolites of the parent drugs themselves in certain assays [2–4]. Common laboratory practice is to concurrently check if common interferents for a given assay are in sufficient quantities to significantly affect results.…”

Section: Discussionmentioning

confidence: 99%

When not to trust therapeutic drug monitoring: Table 1:

et al. 2016

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Therapeutic drug monitoring (TDM) is the measurement of serum or plasma drug concentration to allow the individualization of dosing. We describe the case of a patient who was prescribed inappropriately large doses of vancomycin due to inaccurate TDM. Specifically, our laboratory reported progressively lower vancomycin concentrations despite dose increases. Eventually, when duplicate samples were sent to a different laboratory vancomycin concentrations were found to be in the toxic range. We hypothesize this was due to the patient generating immunoglobulin antibodies against her infection that interfered with the original TDM immunoassay. Immunogenic TDM interference has been known to rarely occur in patients with immune related comorbidities; however, if we are correct, this is a unique case as this patient did not have such a background. This case illustrates the importance of using clinical judgement when interpreting TDM as, in this case, substantial harm to the patient was likely only narrowly avoided.

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Section: Discussionmentioning

confidence: 99%

When not to trust therapeutic drug monitoring: Table 1:

et al. 2016

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“…Additionally, the fragmentation of each of these bifunctional compounds gave rise to MS 3 product ions (Figure S2, supporting information) which can be used to improve analytical selectivity through MRM with multistage fragmentation (MS 3 ) for the quantification of these bifunctional compounds in complex biological matrices where there is an increased possibility of matrix interference with conventional MRM transitions. For example, poor analytical selectivity for quantitation of plasma normetanephrine and metanephrine by LC‐MRM was improved using MRM with multistage fragmentation (MS 3 ) …”

Section: Resultsmentioning

confidence: 99%

“…31 . [32][33][34][35][36] The detailed tandem mass spectrometric fragmentation of these bifunctional compounds is described below.…”

Section: Single-stage Ms Analysismentioning

confidence: 99%

Tandem mass spectrometric analysis of novel caffeine scaffold‐based bifunctional compounds for Parkinson's disease

Nwabufo

El‐Aneed

Krol

2019

Rapid Comm Mass Spectrometry

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Rationale Novel bifunctional compounds composed of a caffeine scaffold attached to nicotine (C8‐6‐N), 1‐aminoindan (C8‐6‐I), or caffeine (C8‐6‐C8) were designed as therapeutics or diagnostics for Parkinson's disease (PD). In order to probe their pharmacological and toxicological profile, an appropriate analytical method is required. The goal of this study is to establish a tandem mass spectrometric fingerprint for the development of quantitative and qualitative methods that will aid future assessment of the in vitro and in vivo absorption, distribution, metabolism, excretion (ADME) and pharmacokinetic properties of these lead bifunctional compounds for PD. Methods Accurate mass measurement was performed using a hybrid quadrupole orthogonal time‐of‐flight mass spectrometer while multistage MS/MS and MS3 analyses were conducted using a triple quadrupole linear ion trap mass spectrometer. Both instruments are equipped with an electrospray ionization (ESI) source and were operated in the positive ion mode. The source and compound parameters were optimized for all three tested bifunctional compounds. Results The MS/MS analysis indicates that the fragmentation of C8‐6‐N and C8‐6‐I is driven by the dissociation of the nicotine and 1‐aminoindan moieties, respectively, but not caffeine. A significant observation in the MS/MS fragmentation of C8‐6‐C8 suggests that a previously reported loss of acetaldehyde during caffeine dissociation is instead a loss of CO2. Conclusions The collision‐induced tandem mass spectrometry (CID‐MS/MS) analysis of these novel bifunctional compounds revealed compound‐specific diagnostic product ions and neutral losses for all three tested bifunctional compounds. The established MS/MS fingerprint will be applied to the future development of qualitative and quantitative methods.

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“…This work will give mechanistic insight into the cellular response to beta-blockers and digoxin, identify novel markers of treatment effect and develop assays that are more robust than serum digoxin concentration (SDC) for determining individual patient dosage. SDC is an immunoassay known to be a poor marker of digoxin toxicity, 70 which can cross-react with other targets 71 (eg, endogenous CTS). Although SDC will be performed at 6 months follow-up and as required during the trial to advise clinicians on dose and avoid high digoxin levels, digoxin toxicity remains a clinical diagnosis at present.…”

Section: Methodsmentioning

confidence: 99%

A review of rate control in atrial fibrillation, and the rationale and protocol for the RATE-AF trial

et al. 2017

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Background and objectiveAtrial fibrillation (AF) is common and causes impaired quality of life, an increased risk of stroke and death as well as frequent hospital admissions. The majority of patients with AF require control of heart rate. In this article, we summarise the limited evidence from clinical trials that guides prescription, and present the rationale and protocol for a new randomised trial. As rate control has not yet been shown to reduce mortality, there is a clear need to compare the impact of therapy on quality of life, cardiac function and exercise capacity. Such a trial should concentrate on the long-term effects of treatment in the largest proportion of patients with AF, those with symptomatic permanent AF, with the aim of improving patient well-being.Design and interventionThe RAte control Therapy Evaluation in permanent Atrial Fibrillation (RATE-AF) trial will enrol 160 participants with a prospective, randomised, open-label, blinded end point design comparing initial rate control with digoxin or bisoprolol. This will be the first head-to-head randomised trial of digoxin and beta-blockers in AF.ParticipantsRecruited patients will be aged ≥60 years with permanent AF and symptoms of breathlessness (equivalent to New York Heart Association class II or above), with few exclusion criteria to maximise generalisability to routine clinical practice.Outcome measuresThe primary outcome is patient-reported quality of life, with secondary outcomes including echocardiographic ventricular function, exercise capacity and biomarkers of cellular and clinical response. Follow-up will occur at 6 and 12 months, with feasibility components to inform the design of a future trial powered to detect a difference in hospital admission. The RATE-AF trial will underpin an integrated approach to management including biomarkers, functions and symptoms that will guide future research into optimal, personalised rate control in patients with AF.Ethics and disseminationEast Midlands-Derby Research Ethics Committee (16/EM/0178); peer-reviewed publications.Trial registrationClinicaltrials.gov: NCT02391337; ISRCTN: 95259705. Pre-results.

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Impact of Interferences Including Metabolite Crossreactivity on Therapeutic Drug Monitoring Results

Cited by 24 publications

References 76 publications

When not to trust therapeutic drug monitoring: Table 1:

When not to trust therapeutic drug monitoring: Table 1:

Tandem mass spectrometric analysis of novel caffeine scaffold‐based bifunctional compounds for Parkinson's disease

A review of rate control in atrial fibrillation, and the rationale and protocol for the RATE-AF trial

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