-
Clinical Mass Spectrometry (Del Mar,... Sep 2019Therapeutic drug monitoring (TDM) uses drug concentrations, primarily from plasma, to optimize drug dosing. Optimisation of drug dosing may improve treatment outcomes,... (Review)
Review
Therapeutic drug monitoring (TDM) uses drug concentrations, primarily from plasma, to optimize drug dosing. Optimisation of drug dosing may improve treatment outcomes, reduce toxicity and reduce the risk of acquired drug resistance. The aim of this narrative review is to outline and discuss the challenges of developing multi-analyte assays for anti-tuberculosis (TB) drugs using liquid chromatography-tandem mass spectrometry (LC-MS/MS) by reviewing the existing literature in the field. Compared to other analytical methods, LC-MS/MS offers higher sensitivity and selectivity while requiring relatively low sample volumes. Additionally, multi-analyte assays are easier to perform since adequate separation and short run times are possible even when non-selective sample preparation techniques are used. However, challenges still exist, especially when optimizing LC separation techniques for assays that include analytes with differing chemical properties. Here, we have identified seven multi-analyte assays for first-line anti-TB drugs that use various solvents for sample preparation and mobile phase separation. Only two multi-analyte assays for second-line anti-TB drugs were identified (including either nine or 20 analytes), with each using different protein precipitation methods, mobile phases and columns. The 20 analyte assay did not include bedaquiline, delamanid, meropenem or imipenem. For these drugs, other assays with similar methodologies were identified that could be incorporated in the development of a future comprehensive multi-analyte assay. TDM is a powerful methodology for monitoring patient's individual treatments in TB programmes, but its implementation will require different approaches depending on available resources. Since TB is most-prevalent in low- and middle-income countries where resources are scarce, a patient-centred approach using sampling methods other than large volume blood draws, such as dried blood spots or saliva collection, could facilitate its adoption and use. Regardless of the methodology of collection and analysis, it will be critical that laboratory proficiency programmes are in place to ensure adequate quality control. It is our intent that the information contained in this review will contribute to the process of assembling comprehensive multiplexed assays for the dynamic monitoring of anti-TB drug treatment in affected individuals.
PubMed: 34934812
DOI: 10.1016/j.clinms.2018.10.002 -
Chemical Society Reviews Jul 2019In contrast to the classical design of a probe with one binding site to target one specific analyte, probes with multiple interaction sites or, alternatively, with... (Review)
Review
In contrast to the classical design of a probe with one binding site to target one specific analyte, probes with multiple interaction sites or, alternatively, with single sites promoting tandem reactions to target one or multiple analytes, have been developed. They have been used in addressing the inherent challenges of selective targeting in the presence of structurally similar compounds and in complex matrices, as well as the visualization of the in vivo interaction or crosstalk between the analytes. Examples of analytes include reactive sulfur species, reactive oxygen species, nucleotides and enzymes. This review focuses on recent innovations in probe design, detection mechanisms and the investigation of biological processes. The vision is to promote the ongoing development of fluorescent probes to enable deeper insight into the physiology of bioactive analytes.
PubMed: 31204740
DOI: 10.1039/c8cs01006d -
Angewandte Chemie (International Ed. in... Sep 2021Electrochemical sensors are indispensable in clinical diagnosis, biochemical detection and environmental monitoring, thanks to their ability to detect analytes in...
Electrochemical sensors are indispensable in clinical diagnosis, biochemical detection and environmental monitoring, thanks to their ability to detect analytes in real-time with direct electronic readout. However, electrochemical sensors are challenged by sensitivity-the need to detect low concentrations, and selectivity-to detect specific analytes in multicomponent systems. Herein, a porphyrinic metal-organic framework (PP-MOF), Mn-PCN-222 is deposited on a conductive indium tin oxide (ITO) surface. It affords Mn-PCN-222/ITO, a versatile voltammetric sensor able to detect redox-active analytes such as inorganic ions, organic hazardous substances and pollutants, including nitroaromatics, phenolic and quinone-hydroquinone toxins, heavy metal ions, biological species, as well as azo dyes. As a working electrode, the high surface area of Mn-PCN-222/ITO enables high currents, and therefore leverages highly sensitive analysis. The metalloporphyrin centre facilitates analyte-specific redox catalysis to simultaneously detect more than one analyte in binary and ternary systems allowing for detection of a wide array of trace pollutants under real-world conditions, most with high sensitivity.
Topics: Biosensing Techniques; Electrochemical Techniques; Environmental Pollutants; Manganese; Metal-Organic Frameworks; Particle Size; Porphyrins; Surface Properties; Trace Elements
PubMed: 34260128
DOI: 10.1002/anie.202107860 -
The AAPS Journal May 2022Decades of discussion and publication have gone into the guidance from the scientific community and the regulatory agencies on the use and validation of pharmacokinetic...
Decades of discussion and publication have gone into the guidance from the scientific community and the regulatory agencies on the use and validation of pharmacokinetic and toxicokinetic assays by chromatographic and ligand binding assays for the measurement of drugs and metabolites. These assay validations are well described in the FDA Guidance on Bioanalytical Methods Validation (BMV, 2018). While the BMV included biomarker assay validation, the focus was on understanding the challenges posed in validating biomarker assays and the importance of having reliable biomarker assays when used for regulatory submissions, rather than definition of the appropriate experiments to be performed. Different from PK bioanalysis, analysis of biomarkers can be challenging due to the presence of target analyte(s) in the control matrices used for calibrator and quality control sample preparation, and greater difficulty in procuring appropriate reference standards representative of the endogenous molecule. Several papers have been published offering recommendations for biomarker assay validation. The situational nature of biomarker applications necessitates fit-for-purpose (FFP) assay validation. A unifying theme for FFP analysis is that method validation requirements be consistent with the proposed context of use (COU) for any given biomarker. This communication provides specific recommendations for biomarker assay validation (BAV) by LC-MS, for both small and large molecule biomarkers. The consensus recommendations include creation of a validation plan that contains definition of the COU of the assay, use of the PK assay validation elements that support the COU, and definition of assay validation elements adapted to fit biomarker assays and the acceptance criteria for both.
Topics: Biological Assay; Biomarkers; Chromatography, Liquid; Mass Spectrometry; Reference Standards
PubMed: 35534647
DOI: 10.1208/s12248-022-00707-z -
Analytical Methods : Advancing Methods... May 2024Paper-based sensors, often referred to as paper-based analytical devices (PADs), stand as a transformative technology in the field of analytical chemistry. They offer an... (Review)
Review
Paper-based sensors, often referred to as paper-based analytical devices (PADs), stand as a transformative technology in the field of analytical chemistry. They offer an affordable, versatile, and accessible solution for diverse analyte detection. These sensors harness the unique properties of paper substrates to provide a cost-effective and adaptable platform for rapid analyte detection, spanning chemical species, biomolecules, and pathogens. This review highlights the key attributes that make paper-based sensors an attractive choice for analyte detection. PADs demonstrate their versatility by accommodating a wide range of analytes, from ions and gases to proteins, nucleic acids, and more, with customizable designs for specific applications. Their user-friendly operation and minimal infrastructure requirements suit point-of-care diagnostics, environmental monitoring, food safety, and more. This review also explores various fabrication methods such as inkjet printing, wax printing, screen printing, dip coating, and photolithography. Incorporating nanomaterials and biorecognition elements promises even more sophisticated and sensitive applications.
Topics: Biosensing Techniques; Paper; Humans; Equipment Design; Environmental Monitoring; Nucleic Acids; Proteins; Nanostructures
PubMed: 38639474
DOI: 10.1039/d3ay02258g -
Molecules (Basel, Switzerland) May 2021Ternary quantum dots (QDs) are novel nanomaterials that can be used in chemical analysis due their unique physicochemical and spectroscopic properties. These properties... (Review)
Review
Ternary quantum dots (QDs) are novel nanomaterials that can be used in chemical analysis due their unique physicochemical and spectroscopic properties. These properties are size-dependent and can be adjusted in the synthetic protocol modifying the reaction medium, time, source of heat, and the ligand used for stabilization. In the last decade, several spectroscopic methods have been developed for the analysis of organic and inorganic analytes in biological, drug, environmental, and food samples, in which different sensing schemes have been applied using ternary quantum dots. This review addresses the different synthetic approaches of ternary quantum dots, the sensing mechanisms involved in the analyte detection, and the predominant areas in which these nanomaterials are used.
PubMed: 34066652
DOI: 10.3390/molecules26092764 -
Progress in Nuclear Magnetic Resonance... Apr 2020Sensing methodologies for the detection of target compounds in mixtures are important in many different contexts, ranging from medical diagnosis to environmental... (Review)
Review
Sensing methodologies for the detection of target compounds in mixtures are important in many different contexts, ranging from medical diagnosis to environmental analysis and quality assessment. Ideally, such detection methods should allow for both identification and quantification of the targets, minimizing the possibility of false positives. With very few exceptions, most of the available sensing techniques rely on the selective interaction of the analyte with some detector, which in turn produces a signal as a result of the interaction. This approach hence provides indirect information on the targets, whose identity is generally ensured by comparison with known standards, if available, or by the selectivity of the sensor system itself. Pursuing a different approach, NMR chemosensing aims at generating signals directly from the analytes, in the form of a (complete) NMR spectrum. In this way, not only are the targets unequivocally identified, but it also becomes possible to identify and assign the structures of unknown species. In this review we show how relaxation- and diffusion-based NMR techniques, assisted by appropriate nanoparticles, can be used to edit the H NMR spectrum of a mixture and extract the signals of specific target compounds. Monolayer-protected nanoparticles, in particular those made from gold, are well suited to this task because they provide a versatile, protein-size support to build or incorporate supramolecular receptors. Remarkably, the self-organized and multifunctional nature of the nanoparticle coating allows exploitation of different kinds of non-covalent interactions, to provide tailored binding sites for virtually any class of molecules. From the NMR standpoint, the reduced translational and rotational diffusion rates of bulky nanoparticles offer a way to manipulate the states of the monolayer spins and build a reservoir of magnetization that can be selectively transferred to the interacting analytes. In addition, the low correlation time and the enhanced rigidity of the coating molecules (due to their grafting and crowding on the particle surface) promote efficient spin diffusion, useful in saturation transfer experiments. The optimized combination of NMR experiments and nanoreceptors can ultimately allow the detection of relevant analytes in the micromolar concentration range, paving the way to applications in the diagnostic field and beyond.
Topics: Chemistry Techniques, Analytical; Magnetic Resonance Spectroscopy; Nanoparticles
PubMed: 32471535
DOI: 10.1016/j.pnmrs.2019.12.001 -
Analytica Chimica Acta Mar 2022There are several challenges associated with LC-MS/MS bioanalytical method development and validation. Low and variable recovery of some analytes, especially the more...
There are several challenges associated with LC-MS/MS bioanalytical method development and validation. Low and variable recovery of some analytes, especially the more hydrophobic ones, is often challenging. Analytes can be lost to various extents throughout the process of sample collection, storage, before, during, and/or after sample preparation and analysis. The calculation of overall extraction recovery can detect problems of low recovery during sample preparation but does not identify the source(s) of analyte losses. Low overall analyte recovery is the net result of losses that can happen for multiple reasons at all steps of sample preparation and analysis. Therefore, identifying the source(s) of analyte loss during sample preparation can help guide the optimization the bioanalysis conditions to minimize these losses. In this article we propose a practical protocol to systematically identify and quantify the sources of low analyte recovery. This allows the proper choice of strategies to optimize the relevant bioanalytical conditions to minimize analyte losses and improve overall recovery.
Topics: Chromatography, Liquid; Specimen Handling; Tandem Mass Spectrometry
PubMed: 35190119
DOI: 10.1016/j.aca.2022.339512 -
Analytical Chemistry Sep 2023The analysis of ions and clusters by mobility-classified mass spectrometry provides information on the mobility of analytes in the drift gas and the analyte mass. Mass...
The analysis of ions and clusters by mobility-classified mass spectrometry provides information on the mobility of analytes in the drift gas and the analyte mass. Mass equivalent and mobility equivalent diameters of globular analytes, such as ions, poly(ethylene glycol) (PEG), and ionic liquid nanodroplets, can be correlated with good accuracy by the Stokes-Millikan mobility model. A prerequisite to such an analysis is, however, the assumption of a globular analyte shape, which then allows determination of material density for globular ions. We show that the analyte density can be evaluated with high precision, independent of any assumptions on the analyte shape, by careful analysis of analyte-PEG-cluster ions following the concept of classical pycnometry. In particular, the analyte is entrapped in a globular PEG-analyte droplet. Based on the now independently derived mobility diameter and volume equivalent diameter, it is possible to attribute two parameters, size and shape, to the analyte molecule. We demonstrate the approach for lysozyme, cyano-cobalamin (vitamin B12), and glucose, which cover two orders of magnitude in analyte mass (180···14 300 Da). The derived densities for these analytes are highly accurate, i.e., they deviate less than 1% from literature values. Our method can be applied to newly synthesized molecules, supramolecular assemblies, isolated biomolecules, and molecular clusters, where only minor amounts of materials are available. The obtained shape parameters of lysozyme and cyano-cobalamin agree well with the expected molecular shapes. Data evaluation relies only on locations of the species in the mass-mobility plane and is in principle independent of any mobility theory. Our approach is thus robust with respect to experimental uncertainties and produces identical results irrespective of the type of mobility classification and drift gas.
PubMed: 37602575
DOI: 10.1021/acs.analchem.3c00625 -
The Analyst Jun 2024The droplet deposition methods in Raman spectroscopy have received considerable attention in the field of analytical sensing focusing on effective pre-concentration of... (Review)
Review
The droplet deposition methods in Raman spectroscopy have received considerable attention in the field of analytical sensing focusing on effective pre-concentration of the studied analyte (coffee-ring effect or small spots). This review covers different analytical applications of drop-coating deposition Raman scattering (DCDRS) and droplet deposition surface-enhanced Raman scattering (SERS) spectroscopy. Two main advantages of droplet deposition Raman techniques are considered: the drying-induced segregation of the components from the mixtures (such as body fluids) and the sensitivity of detection of various analytically important molecules. Some recent advanced applications, including clinical cancer diagnosis, are discussed and summarized. Finally, the potential and further perspectives of the droplet deposition Raman methods for analytical studies are introduced.
PubMed: 38770583
DOI: 10.1039/d4an00336e