Therapeutic Drug Monitoring最新文献

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Continuous Versus Intermittent Administration of Meropenem in Critically Ill Patients. 危重病人持续与间歇服用美罗培南的对比
IF 2.8 4区 医学
Therapeutic Drug Monitoring Pub Date : 2024-10-01 Epub Date: 2024-06-28 DOI: 10.1097/FTD.0000000000001181
Manon Launay, Sophie Perinel-Ragey, Guillaume Thiery
{"title":"Continuous Versus Intermittent Administration of Meropenem in Critically Ill Patients.","authors":"Manon Launay, Sophie Perinel-Ragey, Guillaume Thiery","doi":"10.1097/FTD.0000000000001181","DOIUrl":"10.1097/FTD.0000000000001181","url":null,"abstract":"","PeriodicalId":23052,"journal":{"name":"Therapeutic Drug Monitoring","volume":" ","pages":"692-693"},"PeriodicalIF":2.8,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141477501","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Implementing Pharmacogenetic Testing as a Risk Reduction Strategy for Drug Users: A Letter to the Editor. 实施药物基因检测作为降低吸毒者风险的策略:致编辑的一封信。
IF 2.8 4区 医学
Therapeutic Drug Monitoring Pub Date : 2024-09-26 DOI: 10.1097/FTD.0000000000001262
Guillaume Drevin, Marie Briet, Chadi Abbara
{"title":"Implementing Pharmacogenetic Testing as a Risk Reduction Strategy for Drug Users: A Letter to the Editor.","authors":"Guillaume Drevin, Marie Briet, Chadi Abbara","doi":"10.1097/FTD.0000000000001262","DOIUrl":"https://doi.org/10.1097/FTD.0000000000001262","url":null,"abstract":"","PeriodicalId":23052,"journal":{"name":"Therapeutic Drug Monitoring","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2024-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142354324","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Development and Validation of a High-Performance Liquid Chromatography-Ultraviolet Spectrometry Method for Ampicillin and its Application in Routine Therapeutic Drug Monitoring of Intensive Care Patients. 氨苄西林高效液相色谱-紫外光谱法的开发与验证及其在重症监护患者常规治疗药物监测中的应用
IF 2.8 4区 医学
Therapeutic Drug Monitoring Pub Date : 2024-09-18 DOI: 10.1097/FTD.0000000000001253
Benedict Morath, Linda Schultes, Otto Roman Frey, Anka Christa Röhr, Hannes Christow, Torsten Hoppe-Tichy, Alexander Brinkmann, Ute Chiriac
{"title":"Development and Validation of a High-Performance Liquid Chromatography-Ultraviolet Spectrometry Method for Ampicillin and its Application in Routine Therapeutic Drug Monitoring of Intensive Care Patients.","authors":"Benedict Morath, Linda Schultes, Otto Roman Frey, Anka Christa Röhr, Hannes Christow, Torsten Hoppe-Tichy, Alexander Brinkmann, Ute Chiriac","doi":"10.1097/FTD.0000000000001253","DOIUrl":"https://doi.org/10.1097/FTD.0000000000001253","url":null,"abstract":"<p><strong>Background: </strong>Ampicillin/sulbactam, a combination of a β-lactam and β-lactamase inhibitor, is widely used in clinical settings. However, therapeutic drug monitoring (TDM) of ampicillin is not commonly performed, particularly in intensive care units (ICUs). The purpose of this study was to develop and validate a rapid and cost-effective high-performance liquid chromatography (HPLC)-ultraviolet spectrometry method to quantify ampicillin in human serum and evaluate its clinical application in ICU patients.</p><p><strong>Methods: </strong>Sample cleanup included a protein precipitation protocol, followed by chromatographic separation on a C18 reverse-phase HPLC column within 12.5 minutes using gradient elution of the mobile phase. The assay was validated according to the German Society of Toxicology and Forensic Chemistry criteria. Clinical applications involved the retrospective analysis of TDM data from ICU patients receiving continuous infusion of ampicillin/sulbactam, including the attainment of target ranges and individual predicted and observed pharmacokinetics.</p><p><strong>Results: </strong>The method was robust, with linear relations between the peak area responses and drug concentrations in the range of 2-128 mg/L. The coefficient of variation for precision and the bias for accuracy (both interday and intraday) were less than 10%. Clinical application revealed variable pharmacokinetics of ampicillin in ICU patients (clearance of 0.5-31.2 L/h). TDM-guided dose adjustments achieved good therapeutic drug exposure, with 92.9% of the samples being within the optimal (16-32 mg/L) or quasioptimal (8-48 mg/L) range.</p><p><strong>Conclusions: </strong>This method provides a practical solution for the routine TDM of ampicillin, facilitating individualized dosing strategies to ensure adequate therapeutic drug exposure. Given its simplicity, cost-effectiveness, and clinical relevance, HPLC-ultraviolet spectrometry holds promise for broad implementation in hospital pharmacies and clinical laboratories.</p>","PeriodicalId":23052,"journal":{"name":"Therapeutic Drug Monitoring","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2024-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142296134","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Daptomycin Dosage Optimization in Renal Impairment Using Model-Informed Precision Dosing. 在肾功能不全的情况下,利用模型指导的精确给药优化达托霉素剂量
IF 2.8 4区 医学
Therapeutic Drug Monitoring Pub Date : 2024-09-10 DOI: 10.1097/FTD.0000000000001256
Hamza Sayadi, Yeleen Fromage, Marc Labriffe, Clément Danthu, Caroline Monchaud, Jean-Baptiste Woillard
{"title":"Daptomycin Dosage Optimization in Renal Impairment Using Model-Informed Precision Dosing.","authors":"Hamza Sayadi, Yeleen Fromage, Marc Labriffe, Clément Danthu, Caroline Monchaud, Jean-Baptiste Woillard","doi":"10.1097/FTD.0000000000001256","DOIUrl":"https://doi.org/10.1097/FTD.0000000000001256","url":null,"abstract":"<p><strong>Background: </strong>Daptomycin's efficacy and toxicity are closely related to its exposure, which can vary widely among individuals. The patient, a 59-year-old male with an estimated glomerular filtration rate (eGFR) of 12 mL/min/1.73 m² and a weight of 64 kg, was treated with 850 mg of daptomycin every other day for infective endocarditis caused by methicillin-resistant Staphylococcus aureus (MRSA). For patients with an estimated glomerular filtration rate of less than 30 mL/min/1.73 m², the dosing recommendations are not explicitly defined in the endocarditis guidelines. Subsequently, the pharmacology department was contacted to adjust the dosage.</p><p><strong>Methods: </strong>A population pharmacokinetic model developed by Dvorchik et al. was used for Bayesian estimation of the patient's pharmacokinetic parameters. The 24-hour area under the curve (AUC24) of daptomycin was calculated at steady state using peak and trough plasma samples.</p><p><strong>Results: </strong>The minimum inhibitory concentration (MIC) of the MRSA strain was 0.25 mg/L. An AUC24/MIC ratio below 666 is associated with higher mortality risk, while an AUC24 above 939 h·mg/L correlates with increased risk of muscular toxicity. Initial AUC24 estimation was 1091 h·mg/L. Following a dosage reduction to 700 mg every other day, the AUC24 increased to 1600 h·mg/L. Further reduction to 500 mg every other day brought the AUC24 down to 750 h mg/L, with two subsequent measurements showing consistent AUC24 values of 500 h·mg/L, which is within the target range.</p><p><strong>Conclusions: </strong>Daptomycin ended 6 weeks after the initial negative blood culture, with no adverse effects or recurrence of MRSA infection. This case underscores the need for therapeutic drug monitoring and a multidisciplinary approach to adjust daptomycin doses in patients with renal impairment.</p>","PeriodicalId":23052,"journal":{"name":"Therapeutic Drug Monitoring","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2024-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142296133","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Population Pharmacokinetic Modeling of Pyrazinamide Among Chinese Patients With Drug-Sensitive or Multidrug-Resistant Tuberculosis. 吡嗪酰胺在中国药物敏感或耐多药肺结核患者中的人群药代动力学模型。
IF 2.8 4区 医学
Therapeutic Drug Monitoring Pub Date : 2024-09-06 DOI: 10.1097/FTD.0000000000001255
Shuyan Chen, Weiqiao Rao, Liang Fu, Guohui Liu, Jiancong Zhang, Yunli Liao, Ning Lv, Guofang Deng, Shijin Yang, Liang Lin, Lujin Li, Jiuxin Qu, Siqi Liu, Jin Zou
{"title":"Population Pharmacokinetic Modeling of Pyrazinamide Among Chinese Patients With Drug-Sensitive or Multidrug-Resistant Tuberculosis.","authors":"Shuyan Chen, Weiqiao Rao, Liang Fu, Guohui Liu, Jiancong Zhang, Yunli Liao, Ning Lv, Guofang Deng, Shijin Yang, Liang Lin, Lujin Li, Jiuxin Qu, Siqi Liu, Jin Zou","doi":"10.1097/FTD.0000000000001255","DOIUrl":"https://doi.org/10.1097/FTD.0000000000001255","url":null,"abstract":"<p><strong>Background: </strong>Pyrazinamide is used to treat drug-susceptible (DS) and multidrug-resistant (MDR) tuberculosis (TB). This study aimed to characterize the factors associated with the pharmacokinetic parameters of pyrazinamide and evaluate the disposition of the current regimen, which could provide suggestions for adequate dosing strategies for therapeutic targets.</p><p><strong>Methods: </strong>A population pharmacokinetic model of pyrazinamide was developed based on the data from 499 plasma concentrations from 222 Chinese patients diagnosed with DS or MDR TB. Pyrazinamide exposure was best described using a one-compartment model.</p><p><strong>Results: </strong>No significant differences were observed in the pharmacokinetic parameters between DS and MDR TB. The final covariate model showed that total body weight was the only significant covariate for apparent clearance, which increased by 0.45 L/h with a 10 kg increase in body weight. A simulation showed that for typical subjects weighing 40-80 kg, a fixed dosage of 1500 mg daily had an area under the concentration-time curve from 0 to 24 hours (AUC0-24) of 389.9-716.0 mg·h/L and peak serum concentrations of the drug (Cmax) of 32.2-44.8 mg/L.</p><p><strong>Conclusions: </strong>Fixed pyrazinamide doses of 1500, 1750, and 2000 mg are recommended for patients weighing 40-70, 70-80, and 80-90 kg, respectively, to achieve the exposure targets of AUC0-24 > 363 mg·h/L or Cmax > 35 mg/L to attain efficacy.</p>","PeriodicalId":23052,"journal":{"name":"Therapeutic Drug Monitoring","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2024-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142143380","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Pharmacokinetic and Pharmacodynamic Assessment of Valganciclovir in Infants With Congenital Cytomegalovirus Infection. 缬更昔洛韦在先天性巨细胞病毒感染婴儿中的药代动力学和药效学评估
IF 2.8 4区 医学
Therapeutic Drug Monitoring Pub Date : 2024-09-04 DOI: 10.1097/FTD.0000000000001257
Kotaro Itohara, Kazuhiro Yamamoto, Shunsuke Fujinaka, Mari Hashimoto, Naoki Tamura, Yumi Kitahiro, Tomohiro Omura, Kazumichi Fujioka, Ikuko Yano
{"title":"Pharmacokinetic and Pharmacodynamic Assessment of Valganciclovir in Infants With Congenital Cytomegalovirus Infection.","authors":"Kotaro Itohara, Kazuhiro Yamamoto, Shunsuke Fujinaka, Mari Hashimoto, Naoki Tamura, Yumi Kitahiro, Tomohiro Omura, Kazumichi Fujioka, Ikuko Yano","doi":"10.1097/FTD.0000000000001257","DOIUrl":"https://doi.org/10.1097/FTD.0000000000001257","url":null,"abstract":"<p><strong>Background: </strong>Valganciclovir (VGCV) is administered at a dose of 16 mg/kg 2 times daily for 6 months to treat symptomatic congenital cytomegalovirus (CMV) infections. During the treatment period, approximately 20% of the patients developed grade 3 or higher neutropenia. Currently, information on the pharmacokinetics and pharmacodynamics of ganciclovir, an active metabolite of VGCV, in infants is limited. In the current study, the relationship between ganciclovir concentration and neutropenia was investigated, and a population pharmacokinetic (PPK) model of ganciclovir in infants with symptomatic congenital CMV infection was developed.</p><p><strong>Methods: </strong>Japanese infants who were prescribed oral VGCV for symptomatic congenital CMV infections between July 2017 and January 2021 were included. The relationship between the observed trough ganciclovir concentrations and neutrophil counts was examined. PPK analysis was performed to evaluate the covariates affecting the pharmacokinetics of ganciclovir.</p><p><strong>Results: </strong>Twenty-seven ganciclovir serum samples from 8 patients were analyzed. A moderate negative correlation was observed between the observed trough ganciclovir concentration and neutrophil count. PPK model analysis showed that postmenstrual age (PMA) affected the total body clearance of ganciclovir after correcting for the empirical allometric scaling of body weight. Based on PMA and body weight, a nomogram to achieve the target area under the concentration-time curve from 0 to 24 hours of 40-60 mcg·h·mL-1 of ganciclovir was calculated.</p><p><strong>Conclusions: </strong>The relationship between neutrophil count and ganciclovir trough concentration in infants was clarified. The PPK model showed that the dose of VGCV should be reduced in patients with a low PMA to achieve target exposure.</p>","PeriodicalId":23052,"journal":{"name":"Therapeutic Drug Monitoring","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2024-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142296136","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Association of Plasma Cabozantinib Concentration With Treatment Response and Adverse Events in Japanese Patients With Advanced Renal Cell Carcinoma. 日本晚期肾细胞癌患者血浆中卡博替尼浓度与治疗反应和不良事件的关系
IF 2.8 4区 医学
Therapeutic Drug Monitoring Pub Date : 2024-08-29 DOI: 10.1097/FTD.0000000000001254
Shinichi Maruyama, Hiroaki Kobayashi, Tatsuru Hiraga, Tadatsugu Anno, Tansei Sanjo, Masashi Arai, Masaru Ishida, Hiroshi Kanno, Masaru Kato
{"title":"Association of Plasma Cabozantinib Concentration With Treatment Response and Adverse Events in Japanese Patients With Advanced Renal Cell Carcinoma.","authors":"Shinichi Maruyama, Hiroaki Kobayashi, Tatsuru Hiraga, Tadatsugu Anno, Tansei Sanjo, Masashi Arai, Masaru Ishida, Hiroshi Kanno, Masaru Kato","doi":"10.1097/FTD.0000000000001254","DOIUrl":"https://doi.org/10.1097/FTD.0000000000001254","url":null,"abstract":"<p><strong>Background: </strong>Cabozantinib is highly effective against advanced renal cell carcinoma (RCC). However, approximately 60% of the patients require a dose reduction due to severe adverse events. Although associations between trough concentrations of cabozantinib and its efficacy and safety have been reported in other countries, reports on Japanese patients are unavailable. Therefore, we investigated the association of cabozantinib trough concentration with therapeutic efficacy and adverse events in Japanese patients with RCC and evaluated the usefulness of therapeutic drug monitoring.</p><p><strong>Methods: </strong>In this prospective observational study, we measured the trough concentrations of cabozantinib in 10 Japanese patients with RCC enrolled between May 2022 and September 2023. The associations of trough concentration with treatment response, as determined by RECIST 1.1, and the occurrence of grade 2 or higher adverse events were assessed.</p><p><strong>Results: </strong>Trough concentration was higher in patients with controlled cancer than in those with progressive cancer (1024 ± 352 versus 457 ± 216 ng/mL, P = 0.035). In addition, patients with grade 2 or higher adverse events showed a significantly higher trough concentration than those without (1560 ± 513 versus 807 ± 319 ng/mL, P = 0.032). In particular, grade 2 or higher dysgeusia, anorexia, fatigue, and dyspepsia significantly correlated with trough concentrations.</p><p><strong>Conclusions: </strong>This is the first clinical study to demonstrate a correlation between cabozantinib trough concentration, therapeutic efficacy, and adverse events in Japanese patients with RCC. The therapeutic drug monitoring of cabozantinib could be useful for improving therapeutic efficacy and avoiding serious adverse events.</p>","PeriodicalId":23052,"journal":{"name":"Therapeutic Drug Monitoring","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2024-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142112233","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Dried Blood Spot Method Development and Clinical Validation for the Analysis of Elexacaftor, Elexacaftor-M23, Tezacaftor, Tezacaftor-M1, Ivacaftor, Ivacaftor Carboxylate, and Hydroxymethyl Ivacaftor Using LC-MS/MS. 利用 LC-MS/MS,开发分析 Elexacaftor、Elexacaftor-M23、Tezacaftor、Tezacaftor-M1、Ivacaftor、Ivacaftor Carboxylate 和 Hydroxymethyl Ivacaftor 的干血斑方法并进行临床验证。
IF 2.8 4区 医学
Therapeutic Drug Monitoring Pub Date : 2024-08-27 DOI: 10.1097/FTD.0000000000001231
Steffie E M Vonk, Marloes van der Meer-Vos, Renate Kos, Anne H Neerincx, Suzanne W J Terheggen-Lagro, Josje Altenburg, Anke H Maitland-van der Zee, Ron A A Mathôt, E Marleen Kemper
{"title":"Dried Blood Spot Method Development and Clinical Validation for the Analysis of Elexacaftor, Elexacaftor-M23, Tezacaftor, Tezacaftor-M1, Ivacaftor, Ivacaftor Carboxylate, and Hydroxymethyl Ivacaftor Using LC-MS/MS.","authors":"Steffie E M Vonk, Marloes van der Meer-Vos, Renate Kos, Anne H Neerincx, Suzanne W J Terheggen-Lagro, Josje Altenburg, Anke H Maitland-van der Zee, Ron A A Mathôt, E Marleen Kemper","doi":"10.1097/FTD.0000000000001231","DOIUrl":"10.1097/FTD.0000000000001231","url":null,"abstract":"<p><strong>Background: </strong>The highly effective Cystic Fibrosis Transmembrane conductance Regulator (CFTR) modulator, elexacaftor-tezacaftor-ivacaftor, is now widely being used by people with cystic fibrosis. However, few independent studies have detailed the pharmacokinetics (PK) of CFTR modulators. Blood collection by venipuncture is the gold standard for PK measurements, but it is invasive. The aim of this study was to develop and clinically validate a quantification method for elexacaftor, tezacaftor, ivacaftor, and their main metabolites in dried blood spots (DBSs) using liquid chromatography with tandem mass spectrometry.</p><p><strong>Methods: </strong>Linearity, accuracy, precision, stability, hematocrit (Hct), spot-to-spot carryover, spot volume, and extraction efficiency were validated in DBS for all analytes. The clinical validation of elexacaftor-tezacaftor-ivacaftor in patients was performed by comparing 21 DBS samples with matched plasma samples.</p><p><strong>Results: </strong>The preset requirements for linearity, within-run and between-run accuracy, precision, Hct, spot volume, and extraction efficiency were met. Puncher carryover was observed and resolved by punching 3 blanks after each sample. The samples remained stable and showed no notable degradation across the tested temperatures and time intervals. Corrected DBS values with the Passing-Bablok regression equation showed good agreement in Bland-Altman plots, and acceptance values were within 20% of the mean for a minimum of 67% of the repeats, according to the EMA guidelines.</p><p><strong>Conclusions: </strong>A quantification method for the analysis of elexacaftor, tezacaftor, ivacaftor, and their main metabolites was developed and clinically validated in DBS. This method could be valuable in both clinical care and research to address unanswered PK questions regarding CFTR modulators.</p>","PeriodicalId":23052,"journal":{"name":"Therapeutic Drug Monitoring","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2024-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11554243/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141459470","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Simultaneous Determination of Ripretinib and Its Desmethyl Metabolite in Human Plasma Using LC-MS/MS. 利用 LC-MS/MS 同时测定人体血浆中的瑞普替尼及其去甲基代谢物
IF 2.8 4区 医学
Therapeutic Drug Monitoring Pub Date : 2024-08-06 DOI: 10.1097/FTD.0000000000001245
Zhou-Yi Qian, Ping Wang, Zi-Yi Wang, Yang Zhao, Tian-Tian Du, Hao Xu, Yong-Qing Wang, Lu-Ning Sun
{"title":"Simultaneous Determination of Ripretinib and Its Desmethyl Metabolite in Human Plasma Using LC-MS/MS.","authors":"Zhou-Yi Qian, Ping Wang, Zi-Yi Wang, Yang Zhao, Tian-Tian Du, Hao Xu, Yong-Qing Wang, Lu-Ning Sun","doi":"10.1097/FTD.0000000000001245","DOIUrl":"https://doi.org/10.1097/FTD.0000000000001245","url":null,"abstract":"<p><strong>Background: </strong>Ripretinib, a recently developed tyrosine kinase inhibitor with switch-control abilities, can inhibit both primary and secondary activation of KIT(KIT proto-oncogene receptor tyrosine kinase) and platelet-derived growth factor receptor alpha (PDGFRA) mutants, which contribute to gastrointestinal stromal tumor progression.</p><p><strong>Methods: </strong>In this study, a high-performance liquid chromatography-tandem mass spectrometry method to measure the concentrations of ripretinib and its active desmethyl metabolite DP-5439 in human plasma was developed and validated. Plasma samples were extracted and recovered by precipitation with acetonitrile containing the internal standard and diluted with acetonitrile before analysis. Ripretinib and DP-5439 were separated using chromatography on a Waters ACQUITY UPLC HSS T3 column (2.1 mm × 50 mm, 1.8 μm) with gradient elution using 0.1% formic acid and 5 mM ammonium formate in water as mobile phase A and acetonitrile as mobile phase B. The mobile phase was set to a flow rate of 0.5 mL/min.</p><p><strong>Results: </strong>The calibration curves were linear across the following concentration range: 7.5 to 3000 ng/mL for ripretinib and 10 to 4000 ng/mL for DP-5439. The intraday and interday precisions were approximately 15% for all analytes in the quality control samples. The relative matrix effects in extracted plasma samples (90.3%-108.8% at different levels) were considered acceptable.</p><p><strong>Conclusions: </strong>This method will be a useful tool in oncology to facilitate the further clinical development of ripretinib.</p>","PeriodicalId":23052,"journal":{"name":"Therapeutic Drug Monitoring","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2024-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141902947","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Development and Validation of a Sensitive Liquid Chromatography-Tandem Mass Spectrometry Method for Therapeutic Drug Monitoring of Ceftolozane and Tazobactam in Human Plasma Microsamples. 开发并验证用于人体血浆微量样本中头孢妥仑和他唑巴坦治疗药物监测的灵敏液相色谱-串联质谱法
IF 2.8 4区 医学
Therapeutic Drug Monitoring Pub Date : 2024-08-06 DOI: 10.1097/FTD.0000000000001236
Matteo Conti, Beatrice Giorgi, Milo Gatti, Pierluigi Viale, Federico Pea
{"title":"Development and Validation of a Sensitive Liquid Chromatography-Tandem Mass Spectrometry Method for Therapeutic Drug Monitoring of Ceftolozane and Tazobactam in Human Plasma Microsamples.","authors":"Matteo Conti, Beatrice Giorgi, Milo Gatti, Pierluigi Viale, Federico Pea","doi":"10.1097/FTD.0000000000001236","DOIUrl":"https://doi.org/10.1097/FTD.0000000000001236","url":null,"abstract":"<p><strong>Background: </strong>Ceftolozane/tazobactam (C-T) is a novel beta-lactam/beta-lactamase inhibitor combination approved for the treatment of various infections caused by difficult-to-treat Pseudomonas aeruginosa. In critically ill patients, C-T may exhibit significant pharmacokinetic variability, both between individuals and within individuals, warranting therapeutic drug monitoring for clinical purposes. We aim to develop and validate a novel and sensitive analytical method for concurrently determining C and T in human plasma microsamples (3 μL).</p><p><strong>Methods: </strong>The method was developed using liquid chromatography-tandem mass spectrometry (LC-MS/MS) with positive electrospray ionization and multiple reaction monitoring (MRM) detection modes, employing specific mass transitions for both drugs. Sample preparation was simple, and the chromatographic run lasted only 4 minutes. Validation was conducted according to European Medicines Agency (EMA) guidelines, encompassing specificity, sensitivity, linearity, precision, accuracy, matrix effect, extraction recovery, limit of quantification, and drug stability. The validated method was applied to measure C and T in 32 plasma samples collected from critically ill patients with multidrug-resistant, gram-negative, bacterial infections.</p><p><strong>Results: </strong>The method ensured accurate (BIAS% 2.1-9.6 for C and -2.2 to 15.2 for T) and precise intraday CV% for C: 6.7-5.5; for T: 1.3-8.9; interday CV% for C 6.0-10.8; for T 4.1-10.2) measurements of C-T over a wide concentration range (0.2-200.0 mg/L for C and 0.1-100.0 mg/L for T). Overall, the recovery at quality control concentration levels was high for both C and T (mean values: 90-91 for C and 89-92 for T). Analyte stability was satisfactory in both human plasma and extracts under various storage conditions. The clinical applicability of the assay was confirmed by the reliably quantifying C and T in clinical plasma samples.</p><p><strong>Conclusions: </strong>The developed and validated LC-MS/MS method is sensitive and suitable for monitoring C and T in human plasma microsamples.</p>","PeriodicalId":23052,"journal":{"name":"Therapeutic Drug Monitoring","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2024-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141902945","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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