{"title":"Direct Quantitation of D-serine in Human Plasma by Enantioselective Liquid Chromatography with Tandem Mass Spectrometry and its Application to a Clinical Study","authors":"Estela Skende, Lei Shi, N. Zheng, Yu-Luan Chen","doi":"10.17145/JAB.19.005","DOIUrl":"https://doi.org/10.17145/JAB.19.005","url":null,"abstract":"","PeriodicalId":15014,"journal":{"name":"Journal of Applied Bioanalysis","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2019-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"89668367","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
INTRODUCTION Penicillins constitute a category of bicyclic organic compounds which are characterized by the presence of a β-lactam ring fused with a thiazoline ring, as shown in Figure 1. They appear to be highly effective against bacterial infections. Therefore antibiotics are extensively used by humans and animals by ingestion. These drugs inhibits the enzymes involved in the biosynthesis of the peptidoglycan in the cell wall. the enzymes involved in the biosynthesis of the peptidoglycan in the cell wall. Penicillins are classified, based on the mode of their activity, or according to their efficacy against bacterial β-lactamases, so they can be used as narrow-spectrum antibiotics. There is constantly a great interest for the quantitative determination of penicillins in biofluids for various reasons as for example, the knowledge of the time above the minimum inhibitory concentration (t > MIC) the most determinant ABSTRACT: Penicillin antibiotics are widely used for antibacterial treatment. Quantitative determination of these drugs in bio-fluids is constantly under a great need. HPLC is the more common analytical technique for this purpose. During the last decades, Green Analytical Chemistry is on the rise and is proven a new tendency. Sample preparation, as a crucial step of the analytical procedure, is strongly affected and determined by this new scientific perspective. Therefore, a variety of new microextraction techniques have been developed, which can be combined with the chromatographic determination of biofluids. In this review, current trends and methods of sample preparation are presented, which are appropriate to be used in order to extract penicillin antibiotics from biological samples prior to their HPLC separation. These methods are compatible with the principles of green analytical chemistry, which is an extreme necessity of our era, for both environmental and economic reasons. The evolution and establishment of these microextraction analytical techniques for sample preparation constitute a significant field of modern research due to their importance in the whole analytical procedure. Bioanalytical applications are set in the spotlight.
{"title":"Trends in Sample Preparation for the HPLC Determination of Penicillins in Biofluids","authors":"V. Alampanos, V. Samanidou, I. Papadoyannis","doi":"10.17145/JAB.19.003","DOIUrl":"https://doi.org/10.17145/JAB.19.003","url":null,"abstract":"INTRODUCTION Penicillins constitute a category of bicyclic organic compounds which are characterized by the presence of a β-lactam ring fused with a thiazoline ring, as shown in Figure 1. They appear to be highly effective against bacterial infections. Therefore antibiotics are extensively used by humans and animals by ingestion. These drugs inhibits the enzymes involved in the biosynthesis of the peptidoglycan in the cell wall. the enzymes involved in the biosynthesis of the peptidoglycan in the cell wall. Penicillins are classified, based on the mode of their activity, or according to their efficacy against bacterial β-lactamases, so they can be used as narrow-spectrum antibiotics. There is constantly a great interest for the quantitative determination of penicillins in biofluids for various reasons as for example, the knowledge of the time above the minimum inhibitory concentration (t > MIC) the most determinant ABSTRACT: Penicillin antibiotics are widely used for antibacterial treatment. Quantitative determination of these drugs in bio-fluids is constantly under a great need. HPLC is the more common analytical technique for this purpose. During the last decades, Green Analytical Chemistry is on the rise and is proven a new tendency. Sample preparation, as a crucial step of the analytical procedure, is strongly affected and determined by this new scientific perspective. Therefore, a variety of new microextraction techniques have been developed, which can be combined with the chromatographic determination of biofluids. In this review, current trends and methods of sample preparation are presented, which are appropriate to be used in order to extract penicillin antibiotics from biological samples prior to their HPLC separation. These methods are compatible with the principles of green analytical chemistry, which is an extreme necessity of our era, for both environmental and economic reasons. The evolution and establishment of these microextraction analytical techniques for sample preparation constitute a significant field of modern research due to their importance in the whole analytical procedure. Bioanalytical applications are set in the spotlight.","PeriodicalId":15014,"journal":{"name":"Journal of Applied Bioanalysis","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2019-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"73887724","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Meet our Editorial Board Member: Dr. Kai Wang","authors":"Kai Wang","doi":"10.17145/jab.19.002","DOIUrl":"https://doi.org/10.17145/jab.19.002","url":null,"abstract":"","PeriodicalId":15014,"journal":{"name":"Journal of Applied Bioanalysis","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2019-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"74663316","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
A. Märtson, K. V. Hateren, G. Bosch, T. Werf, D. Touw, J. Alffenaar
Abstract OBJECTIVES: Currently there is no data about a liquid chromatography tandem mass spectrometry (LC-MS/MS) assay including ganciclovir and acyclovir using stable-isotopically labeled internal standards. METHODS: LC-MS/MS assay for measurement of ganciclovir and acyclovir using deuterated standards: ganciclovir-[2H5] and acyclovir-[2H4] was developed. The selectivity and sensitivity, linearity, accuracy and precision, recovery, matrix effect, stability, total process efficiency, carry-over and dilution integrity were validated based on EMA and FDA guidelines. RESULTS: The retention time for ganciclovir was 1.1 min and for acyclovir 1.35 min. Calibration curves were linear over a range of 0.1 to 20 mg/L and the correlation coefficient (R2) was 0.99912 for ganciclovir and 0.99945 for acyclovir. The calculated accuracy was –2.0% to 3.1% for ganciclovir and –1.0% to 6.4% for acyclovir. Within-day precision ranged from 1.8% to 6.6% for ganciclovir and 1.6 % to 6.5% for acyclovir and between-day precision 0% to 9.6% for ganciclovir and 0% to 7.9% for acyclovir. CONCLUSIONS: A rapid and validated LC-MS/MS method was developed for measurement of ganciclovir and acyclovir in human serum which can be used in routine patient care and clinical research.
{"title":"Determination of Ganciclovir and Acyclovir in Human Serum using Liquid Chromatography-Tandem Mass Spectrometry","authors":"A. Märtson, K. V. Hateren, G. Bosch, T. Werf, D. Touw, J. Alffenaar","doi":"10.17145/JAB.18.022","DOIUrl":"https://doi.org/10.17145/JAB.18.022","url":null,"abstract":"Abstract OBJECTIVES: Currently there is no data about a liquid chromatography tandem mass spectrometry (LC-MS/MS) assay including ganciclovir and acyclovir using stable-isotopically labeled internal standards. METHODS: LC-MS/MS assay for measurement of ganciclovir and acyclovir using deuterated standards: ganciclovir-[2H5] and acyclovir-[2H4] was developed. The selectivity and sensitivity, linearity, accuracy and precision, recovery, matrix effect, stability, total process efficiency, carry-over and dilution integrity were validated based on EMA and FDA guidelines. RESULTS: The retention time for ganciclovir was 1.1 min and for acyclovir 1.35 min. Calibration curves were linear over a range of 0.1 to 20 mg/L and the correlation coefficient (R2) was 0.99912 for ganciclovir and 0.99945 for acyclovir. The calculated accuracy was –2.0% to 3.1% for ganciclovir and –1.0% to 6.4% for acyclovir. Within-day precision ranged from 1.8% to 6.6% for ganciclovir and 1.6 % to 6.5% for acyclovir and between-day precision 0% to 9.6% for ganciclovir and 0% to 7.9% for acyclovir. CONCLUSIONS: A rapid and validated LC-MS/MS method was developed for measurement of ganciclovir and acyclovir in human serum which can be used in routine patient care and clinical research.","PeriodicalId":15014,"journal":{"name":"Journal of Applied Bioanalysis","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2018-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"76901381","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Competing interests: The authors have declared that competing interest exist. 1Center for Clinical Pharmacology, Children’s Hospital of Philadelphia, Philadelphia, USA. 2Department of Anesthesiology and Critical Care Medicine, Children’s Hospital of Philadelphia, Philadelphia, USA. 3Division of Infectious Diseases, Children’s Hospital of Philadelphia, Philadelphia, USA. 4Department of Pediatrics, Children’s Hospital of Philadelphia, and Perelman School of Medicine, University of Pennsylvania, Philadelphia, USA.
{"title":"Liquid Chromatography-Tandem Mass Spectrometry Assays for Therapeutic Drug Monitoring of Cefepime","authors":"G. Moorthy, K. Downes, Nicole R. Zane, A. Zuppa","doi":"10.17145/JAB.18.019","DOIUrl":"https://doi.org/10.17145/JAB.18.019","url":null,"abstract":"Competing interests: The authors have declared that competing interest exist. 1Center for Clinical Pharmacology, Children’s Hospital of Philadelphia, Philadelphia, USA. 2Department of Anesthesiology and Critical Care Medicine, Children’s Hospital of Philadelphia, Philadelphia, USA. 3Division of Infectious Diseases, Children’s Hospital of Philadelphia, Philadelphia, USA. 4Department of Pediatrics, Children’s Hospital of Philadelphia, and Perelman School of Medicine, University of Pennsylvania, Philadelphia, USA.","PeriodicalId":15014,"journal":{"name":"Journal of Applied Bioanalysis","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2018-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"89511205","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
OBJECTIVES: Flucytosine is an important drug for the combination treatment of cryptococcal meningitis in patients suffering from an infection with human immunodeficiency virus. As new synergistic regimens are being explored in clinical trials a full oral regimen may be near. For such a study evaluation of drug exposure is of critical importance as bioavailability could be compromised and elimination highly depends on renal function. No simple LC-MS/MS method for therapeutic drug monitoring of flucytosine has been published.
{"title":"Determination of Flucytosine in Human Serum using Liquid Chromatography-Tandem Mass Spectrometry","authors":"J. Alffenaar, K. V. Hateren, D. Touw","doi":"10.17145/jab.18.020","DOIUrl":"https://doi.org/10.17145/jab.18.020","url":null,"abstract":"OBJECTIVES: Flucytosine is an important drug for the combination treatment of cryptococcal meningitis in patients suffering from an infection with human immunodeficiency virus. As new synergistic regimens are being explored in clinical trials a full oral regimen may be near. For such a study evaluation of drug exposure is of critical importance as bioavailability could be compromised and elimination highly depends on renal function. No simple LC-MS/MS method for therapeutic drug monitoring of flucytosine has been published.","PeriodicalId":15014,"journal":{"name":"Journal of Applied Bioanalysis","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2018-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"74415760","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Making a Difference in Therapeutic Drug Monitoring of Antimicrobial Drugs; the Need for LC-MS/MS","authors":"J. Alffenaar, D. Touw","doi":"10.17145/jab.18.018","DOIUrl":"https://doi.org/10.17145/jab.18.018","url":null,"abstract":"","PeriodicalId":15014,"journal":{"name":"Journal of Applied Bioanalysis","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2018-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"77715194","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Noortje J D Mabelis, Kimberly N. Shudofsky, J. J. V. Raaij, S. Meenks, T. Havenith, S. Croes, J. L. L. Noble, P. Janssen
OBJECTIVES: To develop a reliable ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method for therapeutic drug monitoring (TDM) of unbound ciprofloxacin concentrations in critically ill patients. METHODS: Total and unbound ciprofloxacin concentrations of five randomly selected intensive care unit (ICU) patients were measured using UPLC-MS/MS. Method validation included accuracy, linearity, precision, repeatability, and limits of detection and quantification. RESULTS: The median unbound ciprofloxacin fraction was 74.8%, with a median area under the curve from 0-24 h (AUC0-24) and maximum serum concentration (Cmax) of 28.51 h·mg/L and 4.45 mg/L respectively. Median free AUC0-24 (fAUC0-24) and free Cmax (fCmax) were 21.57 h·mg/L and 3.53 mg/L respectively; 20% of patients reached the pharmacodynamic target. The UPLC-MS/ MS method was validated using an intra-assay and inter-assay precision < 3%. Recoveries were between 90-110% CONCLUSIONS: This UPLC-MS/MS method provided reliable unbound ciprofloxacin concentrations, allowing target attainment in critically ill patients and exploration of different dosing regimens.
{"title":"Therapeutic Drug Monitoring of Protein Unbound Ciprofloxacin Concentrations to avoid inadequate Treatment of severe Bacterial Infections in Critically ill Patients","authors":"Noortje J D Mabelis, Kimberly N. Shudofsky, J. J. V. Raaij, S. Meenks, T. Havenith, S. Croes, J. L. L. Noble, P. Janssen","doi":"10.17145/JAB.18.021","DOIUrl":"https://doi.org/10.17145/JAB.18.021","url":null,"abstract":"OBJECTIVES: To develop a reliable ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method for therapeutic drug monitoring (TDM) of unbound ciprofloxacin concentrations in critically ill patients. METHODS: Total and unbound ciprofloxacin concentrations of five randomly selected intensive care unit (ICU) patients were measured using UPLC-MS/MS. Method validation included accuracy, linearity, precision, repeatability, and limits of detection and quantification. RESULTS: The median unbound ciprofloxacin fraction was 74.8%, with a median area under the curve from 0-24 h (AUC0-24) and maximum serum concentration (Cmax) of 28.51 h·mg/L and 4.45 mg/L respectively. Median free AUC0-24 (fAUC0-24) and free Cmax (fCmax) were 21.57 h·mg/L and 3.53 mg/L respectively; 20% of patients reached the pharmacodynamic target. The UPLC-MS/ MS method was validated using an intra-assay and inter-assay precision < 3%. Recoveries were between 90-110% CONCLUSIONS: This UPLC-MS/MS method provided reliable unbound ciprofloxacin concentrations, allowing target attainment in critically ill patients and exploration of different dosing regimens.","PeriodicalId":15014,"journal":{"name":"Journal of Applied Bioanalysis","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2018-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"73110677","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
INTRODUCTION Molecular recognition is one of the most important events in biological systems. The characterization of molecular interactions is a fascinating research area, fundamental to understand the function of biomolecules and to develop new bioactive compounds (drugs). The comprehensive thermodynamic and kinetic characterization of a binding event requires monitoring the formation of the complex(es) as a function of the concentration of reactants or as a function of time, and the subsequent data analysis using a mathematical model that describes the binding process monitored. During the past years, the growing interest in the field of molecular recognition has been reflected in a considerable improvement in the instruments sensitivity of well stablished biophysical techniques and in the development of new ones; yet less has been investigated in the development and optimization of new analysis tools for a reliable understanding of binding data, and here is where the software AFFINImeter has stepped in. AFFINImeter [1] is a shareware software for the general analysis of binding experiments. It was born upon the need of a tool for the analysis of isothermal titration calorimetry (ITC) measurements that could handle complex interactions in an easyto-use way. Since it was released as a cloud-based software in 2015 many scientist from academic labs, research institutes and pharmaceutical companies are being benefited from the advanced tools that AFFINImeter offers for the reliable characterization of interactions by ITC; at present, AFFINImeter has been adapted for the analysis of titration data generated from different biophysical techniques popular in drug design and discovery programs such as nuclear magnetic resonance (NMR), general spectrometric methods or Microscale thermophoresis (MST).
{"title":"AFFINImeter Software: from its Beginnings to Future Trends- A Literature review","authors":"E. Vegas Muñoz, Ángel Piñeiro","doi":"10.17145/JAB.18.017","DOIUrl":"https://doi.org/10.17145/JAB.18.017","url":null,"abstract":"INTRODUCTION Molecular recognition is one of the most important events in biological systems. The characterization of molecular interactions is a fascinating research area, fundamental to understand the function of biomolecules and to develop new bioactive compounds (drugs). The comprehensive thermodynamic and kinetic characterization of a binding event requires monitoring the formation of the complex(es) as a function of the concentration of reactants or as a function of time, and the subsequent data analysis using a mathematical model that describes the binding process monitored. During the past years, the growing interest in the field of molecular recognition has been reflected in a considerable improvement in the instruments sensitivity of well stablished biophysical techniques and in the development of new ones; yet less has been investigated in the development and optimization of new analysis tools for a reliable understanding of binding data, and here is where the software AFFINImeter has stepped in. AFFINImeter [1] is a shareware software for the general analysis of binding experiments. It was born upon the need of a tool for the analysis of isothermal titration calorimetry (ITC) measurements that could handle complex interactions in an easyto-use way. Since it was released as a cloud-based software in 2015 many scientist from academic labs, research institutes and pharmaceutical companies are being benefited from the advanced tools that AFFINImeter offers for the reliable characterization of interactions by ITC; at present, AFFINImeter has been adapted for the analysis of titration data generated from different biophysical techniques popular in drug design and discovery programs such as nuclear magnetic resonance (NMR), general spectrometric methods or Microscale thermophoresis (MST).","PeriodicalId":15014,"journal":{"name":"Journal of Applied Bioanalysis","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2018-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"80914274","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}