Quantification of teicoplanin in plasma by LC-MS with online sample clean-up and comparison with QMS® assay

Müller, Daniel; Eckardstein, Arnold von; Saleh, Lanja

doi:10.1515/cclm-2013-0974

Cited by 17 publications

(4 citation statements)

References 25 publications

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“… 11 , 12 , 14 , 23 , 30 None of these assays fulfilled all desired criteria for use in clinical practice and for research purposes. In comparison with previously published assays able to measure unbound teicoplanin, 6 , 27 , 28 , 30 the assay described in this paper has a significantly reduced runtime of 5.5 mins. Labour intensity and sample preparation time facilitate application of this assay in clinical practice.…”

Section: Discussionmentioning

confidence: 88%

Development and validation of a bioanalytical assay for the measurement of total and unbound teicoplanin in human serum

Mouton,

Raaijmakers,

Botterblom

et al. 2023

Journal of Antimicrobial Chemotherapy

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Background The glycopeptide teicoplanin is considered first-line treatment for severe infections caused by Gram-positive bacteria. Individualized treatment of teicoplanin is gaining interest. As only protein-unbound drug is pharmacologically active, a sensitive assay measuring unbound and total teicoplanin is indispensable for pharmacological research and dose optimization. Objectives To develop and validate a UPLC-MS/MS method to quantify unbound and total teicoplanin in human serum. Methods The developed assay was validated according to the ICH guideline M10 on Bioanalytical Method Validation and study sample analysis. Unbound teicoplanin was obtained by ultrafiltration. The assay was cross-validated with a quantitative microsphere (QMS) immunoassay in a side-by-side comparison using 40 patient samples. Results With the developed and validated method, all main teicoplanin components (A2-1, A2-2/A2-3, A2-4/A2-5 and A3-1) can be quantified. Total run time was 5.5 min. Concentration range was 2.5–150 mg/L for total and 0.1–25 mg/L for unbound teicoplanin. Precision (coefficient of variation) and accuracy (bias) of total teicoplanin were 5.97% and 107%, respectively, and 7.17% and 108%, respectively, for unbound teicoplanin. Bland–Altman analysis showed total concentrations measured with the UPLC-MS/MS method were equivalent to the results of the QMS immunoassay. A total of 188 samples from 30 patients admitted to the ICU and haematology department were measured; total concentrations ranged between 2.92 and 98.5 mg/L, and unbound concentrations ranged between 0.37 and 30.7 mg/L. Conclusions The developed method provided rapid, precise and accurate measurement of unbound and total teicoplanin. The developed method is now routinely applied in pharmacological research and clinical practice.

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Section: Discussionmentioning

confidence: 88%

Development and validation of a bioanalytical assay for the measurement of total and unbound teicoplanin in human serum

Mouton,

Raaijmakers,

Botterblom

et al. 2023

Journal of Antimicrobial Chemotherapy

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“…It is important to take into account potential differences in a bio-analysis method. Immunoassays suffer from non-specific interferences because the used antibodies can also interact with compounds other than the main teicoplanin isomorphic compounds [34,35]. 1.…”

Section: Discussionmentioning

confidence: 99%

Population Pharmacokinetics of Unbound and Total Teicoplanin in Critically Ill Pediatric Patients

et al. 2020

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Background and Objectives Teicoplanin is a highly protein-bound antibiotic, increasingly used to treat serious Gram-positive infections in critically ill children. Maturational and pathophysiological intensive care unit-related changes often lead to altered pharmacokinetics. In this study, the objectives were to develop a pediatric population-pharmacokinetic model of unbound and total teicoplanin concentrations, to investigate the impact of plasma albumin levels and renal function on teicoplanin pharmacokinetics, and to evaluate the efficacy of the current weight-based dosing regimen. Methods An observational pharmacokinetic study was performed and blood samples were collected for quantification of unbound and total concentrations of teicoplanin after the first dose and in assumed steady-state conditions. A populationpharmacokinetic analysis was conducted using a standard sequential approach and Monte Carlo simulations were performed for a probability of target attainment analysis using previously published pharmacokinetic-pharmacodynamic targets. Results A two-compartment model with allometric scaling of pharmacokinetic parameters and non-linear plasma protein binding best described the data. Neither the inclusion of albumin nor the renal function significantly improved the model and no other covariates were supported for inclusion in the final model. The probability of target attainment analysis showed that the standard dosing regimen does not satisfactory attain the majority of the proposed targets. Conclusions We successfully characterized the pharmacokinetics of unbound and total teicoplanin in critically ill pediatric patients. The highly variable unbound fraction of teicoplanin could not be predicted using albumin levels, which may support the use of therapeutic drug monitoring of unbound concentrations. Poor target attainment was shown for the most commonly used dosing regimen, regardless of the pharmacokinetic-pharmacodynamic target evaluated.

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“…Samples were promptly refrigerated and centrifuged at 2500 × g for 10 min before 2 mL of supernatant was preserved at -20 °C for subsequent analysis. Teicoplanin concentrations were determined using liquid chromatography-tandem mass spectrometry [20][21][22]. The linear range of the method was 1.0-100.0 mg/L, and the lower limit of quantification was 1.0 mg/L.…”

Section: Blood Sampling Measurement and Therapeutic Drug Monitoring (...mentioning

confidence: 99%

Necessity for higher teicoplanin doses in older adults: a multicenter prospective observational study in China

Liu,

Wu,

et al. 2024

BMC Geriatr

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Background Many older adult patients receive low-dose teicoplanin with varied regimens, leading to a lack of clarity on its optimal regimens and toxicity profiles in China. This study aimed to clarify these aspects by analyzing teicoplanin treatment concentrations and toxicities. Methods We included older adult patients administered teicoplanin at four tertiary hospitals in Beijing from June 2021 to July 2023, targeting a trough concentration (Cmin) ≥ 10 mg/L. Teicoplanin concentrations and toxicities were monitored dynamically. Results From 204 patients, we obtained 632 teicoplanin concentrations. Most patients (83.3%) received low-dose regimens. Suboptimal concentrations were found in 66.4% of patients within 7 days of treatment and 17.0% after 15 days. Cmin gradually increased with treatment duration and was influenced initially by creatinine and by both body weight and creatinine from days 8 to 14. The target concentration was achieved in 53.1%, 33.9%, 15.6%, and 5.5% of patients at 3, ≤ 7, 8–14, and ≥ 15 days after withdrawal, respectively. Slow elimination was associated with average Cmin and eGFR. Nephrotoxicity, hepatotoxicity, and thrombocytopenia occurred in 12.5%, 4.1%, and 31.5% of patients, respectively, without significant differences between concentrations. Conclusions Most older adult patients were underdosed, indicating a need for dose adjustment. Given the varied risk factors for suboptimal concentrations in different treatment stages, a one-size-fits-all regimen was ineffective. We recommend an initial dose of 400 mg at 12-h intervals for the first three days, with subsequent doses from days 4 to 14 adjusted based on creatinine and body weight; after day 14, a maintenance dose of 200 mg daily is advised. Trial registration ChiCTR2100046811; 28/05/2021.

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Quantification of teicoplanin in plasma by LC-MS with online sample clean-up and comparison with QMS® assay

Abstract: This specific, automated, LC-MS assay for teicoplanin is suitable for therapeutic drug monitoring.

Cited by 17 publications

References 25 publications

Development and validation of a bioanalytical assay for the measurement of total and unbound teicoplanin in human serum

Development and validation of a bioanalytical assay for the measurement of total and unbound teicoplanin in human serum

Population Pharmacokinetics of Unbound and Total Teicoplanin in Critically Ill Pediatric Patients

Necessity for higher teicoplanin doses in older adults: a multicenter prospective observational study in China

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