Xiaoxiao Li, Pan Chang, Xing Liu, Deying Gong, Wensheng Zhang
{"title":"Rapid quantification and PK-PD modeling of rocuronium bromide in beagles using portable mass spectrometer.","authors":"Xiaoxiao Li, Pan Chang, Xing Liu, Deying Gong, Wensheng Zhang","doi":"10.3389/fvets.2025.1543086","DOIUrl":null,"url":null,"abstract":"<p><p>Monitoring rocuronium bromide (Rocur) concentrations is crucial for assessing muscle relaxation in clinical anesthesia. However, no suitable instruments are currently available. This study explores the application of a portable mass spectrometer (MS) for the rapid detection of Rocur concentrations in whole blood from beagles, aiming to support the development of individualized pharmacokinetic-pharmacodynamic (PK-PD) models. Four beagles (1-1.5 years old, 8-12 kg) received a single intravenous dose of Rocur (3 ED₅₀, 0.748 mg/kg). Neuromuscular monitoring was conducted using the train of four (TOF) ratio. Blood samples (0.1 mL) were collected at predetermined intervals and during recovery, with TOF ratios recorded at corresponding time points. Rocur concentrations in whole blood (C<sub>b-Rocur</sub>) were quantified using both the Cell portable MS and high-performance liquid chromatography with mass spectrometry (HPLC-MS) for consistency assessment. Additionally, a PK-PD model was developed based on C<sub>b-Rocur</sub> measurements obtained from the Cell portable MS. A strong linear relationship was observed for Cell portable MS measurements within the range of 50-10,000 ng/mL (<i>y</i> = 1108.32 * <i>x</i> + 14873.99, <i>R</i> <sup>2</sup> = 0.993), with a limit of quantification (LOQ) of 50 ng/mL and a limit of detection (LOD) of 10 ng/mL. A strong linear correlation was found between the two techniques (<i>y</i> = 1.07 * <i>x</i> + 30.08, <i>p</i> < 0.0001, <i>R</i> <sup>2</sup> = 0.8948), with a relative standard deviation <15% for all concentrations. The C<sub>max</sub> values were 4.52 ± 1.16 μg/mL (Cell portable MS) and 4.89 ± 0.52 μg/mL (HPLC-MS), respectively. As C<sub>b-Rocur</sub> decreased, the TOF ratio gradually recovered, with an IC<sub>50</sub> of 0.25 ± 0.05 μg/mL. This study successfully applied the Cell portable MS for rapid quantitative Rocur analysis in whole blood, demonstrating high consistency with HPLC-MS. The findings also revealed the good correlation between the PK-PD properties of Rocur and TOF effects.</p>","PeriodicalId":12772,"journal":{"name":"Frontiers in Veterinary Science","volume":"12 ","pages":"1543086"},"PeriodicalIF":2.6000,"publicationDate":"2025-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11914140/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Frontiers in Veterinary Science","FirstCategoryId":"97","ListUrlMain":"https://doi.org/10.3389/fvets.2025.1543086","RegionNum":2,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2025/1/1 0:00:00","PubModel":"eCollection","JCR":"Q1","JCRName":"VETERINARY SCIENCES","Score":null,"Total":0}
引用次数: 0
Abstract
Monitoring rocuronium bromide (Rocur) concentrations is crucial for assessing muscle relaxation in clinical anesthesia. However, no suitable instruments are currently available. This study explores the application of a portable mass spectrometer (MS) for the rapid detection of Rocur concentrations in whole blood from beagles, aiming to support the development of individualized pharmacokinetic-pharmacodynamic (PK-PD) models. Four beagles (1-1.5 years old, 8-12 kg) received a single intravenous dose of Rocur (3 ED₅₀, 0.748 mg/kg). Neuromuscular monitoring was conducted using the train of four (TOF) ratio. Blood samples (0.1 mL) were collected at predetermined intervals and during recovery, with TOF ratios recorded at corresponding time points. Rocur concentrations in whole blood (Cb-Rocur) were quantified using both the Cell portable MS and high-performance liquid chromatography with mass spectrometry (HPLC-MS) for consistency assessment. Additionally, a PK-PD model was developed based on Cb-Rocur measurements obtained from the Cell portable MS. A strong linear relationship was observed for Cell portable MS measurements within the range of 50-10,000 ng/mL (y = 1108.32 * x + 14873.99, R2 = 0.993), with a limit of quantification (LOQ) of 50 ng/mL and a limit of detection (LOD) of 10 ng/mL. A strong linear correlation was found between the two techniques (y = 1.07 * x + 30.08, p < 0.0001, R2 = 0.8948), with a relative standard deviation <15% for all concentrations. The Cmax values were 4.52 ± 1.16 μg/mL (Cell portable MS) and 4.89 ± 0.52 μg/mL (HPLC-MS), respectively. As Cb-Rocur decreased, the TOF ratio gradually recovered, with an IC50 of 0.25 ± 0.05 μg/mL. This study successfully applied the Cell portable MS for rapid quantitative Rocur analysis in whole blood, demonstrating high consistency with HPLC-MS. The findings also revealed the good correlation between the PK-PD properties of Rocur and TOF effects.
期刊介绍：
Frontiers in Veterinary Science is a global, peer-reviewed, Open Access journal that bridges animal and human health, brings a comparative approach to medical and surgical challenges, and advances innovative biotechnology and therapy.
Veterinary research today is interdisciplinary, collaborative, and socially relevant, transforming how we understand and investigate animal health and disease. Fundamental research in emerging infectious diseases, predictive genomics, stem cell therapy, and translational modelling is grounded within the integrative social context of public and environmental health, wildlife conservation, novel biomarkers, societal well-being, and cutting-edge clinical practice and specialization. Frontiers in Veterinary Science brings a 21st-century approach—networked, collaborative, and Open Access—to communicate this progress and innovation to both the specialist and to the wider audience of readers in the field.
Frontiers in Veterinary Science publishes articles on outstanding discoveries across a wide spectrum of translational, foundational, and clinical research. The journal''s mission is to bring all relevant veterinary sciences together on a single platform with the goal of improving animal and human health.
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