Pub Date : 2024-08-10DOI: 10.1007/s00216-024-05476-6
Natalia Gabrielly Pereira Dos Santos, Deyber Arley Vargas Medina, Fernando Mauro Lanças
Water, renowned for its sustainability and minimal toxicity, is an ideal candidate for environmentally friendly solvent-based microextraction. However, its potential as an extractant solvent in miniaturized sample preparation remains largely unexplored. This paper pioneers using water as the extraction solvent in headspace single-drop microextraction (HS-SDME) for N-nitrosamines from losartan tablets. Autonomous HS-SDME is executed by an Arduino-controlled, lab-made Cartesian robot, using water for the online preconcentration of enriched extracts through direct injection into a column-switching system. Critical experimental parameters influencing HS-SDME performance are systematically explored through univariate and multivariate experiments. While most previously reported methods for determining N-nitrosamines in pharmaceutical formulations rely on highly selective mass spectrometry detection techniques to handle the strong matrix effects typical of pharmaceutical samples, the water-based HS-SDME method efficiently eliminates the interfering effects of a large amount of the pharmaceutical active ingredient and tablet excipients, allowing straightforward analysis using high-performance liquid chromatography with ultraviolet detection (HPLC-UV-Vis). Under optimized conditions, the developed method exhibits linear responses from 100 to 2400 ng g-1, demonstrating appropriate detectability, precision, and accuracy for the proposed application. Additionally, the environmental sustainability of the method is assessed using the AGREEprep methodology, positioning it as an outstanding green alternative for determining hazardous contaminants in pharmaceutical products.
{"title":"Water as a green solvent for sustainable sample preparation: single drop microextraction of N-nitrosamines from losartan tablets.","authors":"Natalia Gabrielly Pereira Dos Santos, Deyber Arley Vargas Medina, Fernando Mauro Lanças","doi":"10.1007/s00216-024-05476-6","DOIUrl":"https://doi.org/10.1007/s00216-024-05476-6","url":null,"abstract":"<p><p>Water, renowned for its sustainability and minimal toxicity, is an ideal candidate for environmentally friendly solvent-based microextraction. However, its potential as an extractant solvent in miniaturized sample preparation remains largely unexplored. This paper pioneers using water as the extraction solvent in headspace single-drop microextraction (HS-SDME) for N-nitrosamines from losartan tablets. Autonomous HS-SDME is executed by an Arduino-controlled, lab-made Cartesian robot, using water for the online preconcentration of enriched extracts through direct injection into a column-switching system. Critical experimental parameters influencing HS-SDME performance are systematically explored through univariate and multivariate experiments. While most previously reported methods for determining N-nitrosamines in pharmaceutical formulations rely on highly selective mass spectrometry detection techniques to handle the strong matrix effects typical of pharmaceutical samples, the water-based HS-SDME method efficiently eliminates the interfering effects of a large amount of the pharmaceutical active ingredient and tablet excipients, allowing straightforward analysis using high-performance liquid chromatography with ultraviolet detection (HPLC-UV-Vis). Under optimized conditions, the developed method exhibits linear responses from 100 to 2400 ng g<sup>-1</sup>, demonstrating appropriate detectability, precision, and accuracy for the proposed application. Additionally, the environmental sustainability of the method is assessed using the AGREEprep methodology, positioning it as an outstanding green alternative for determining hazardous contaminants in pharmaceutical products.</p>","PeriodicalId":462,"journal":{"name":"Analytical and Bioanalytical Chemistry","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2024-08-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141911248","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Understanding the relationship between the concentration of a drug and its therapeutic efficacy or side effects is crucial in drug development, especially to understand therapeutic efficacy in central nervous system drug, quantifying drug-induced site-specific changes in the levels of endogenous metabolites, such as neurotransmitters. In recent times, evaluation of quantitative distribution of drugs and endogenous metabolites using matrix-assisted laser desorption/ionization (MALDI)-mass spectrometry imaging (MSI) has attracted much attention in drug discovery research. However, MALDI-MSI quantification (quantitative mass spectrometry imaging, QMSI) is an emerging technique, and needs to be further developed for practicable and convenient use in drug discovery research. In this study, we developed a reliable QMSI method for quantification of clozapine (antipsychotic drug) and dopamine and its metabolites in the rat brain using MALDI-MSI. An improved mimetic tissue model using powdered frozen tissue for QMSI was established as an alternative method, enabling the accurate quantification of clozapine levels in the rat brain. Furthermore, we used the improved method to evaluate drug-induced fluctuations in the concentrations of dopamine and its metabolites. This method can quantitatively evaluate drug localization in the brain and drug-induced changes in the concentration of endogenous metabolites, demonstrating the usefulness of QMSI.
{"title":"Novel mimetic tissue standards for precise quantitative mass spectrometry imaging of drug and neurotransmitter concentrations in rat brain tissues.","authors":"Kenichi Watanabe, Sayo Takayama, Toichiro Yamada, Masayo Hashimoto, Jun Tadano, Tetsuya Nakagawa, Takao Watanabe, Eiichiro Fukusaki, Izuru Miyawaki, Shuichi Shimma","doi":"10.1007/s00216-024-05477-5","DOIUrl":"https://doi.org/10.1007/s00216-024-05477-5","url":null,"abstract":"<p><p>Understanding the relationship between the concentration of a drug and its therapeutic efficacy or side effects is crucial in drug development, especially to understand therapeutic efficacy in central nervous system drug, quantifying drug-induced site-specific changes in the levels of endogenous metabolites, such as neurotransmitters. In recent times, evaluation of quantitative distribution of drugs and endogenous metabolites using matrix-assisted laser desorption/ionization (MALDI)-mass spectrometry imaging (MSI) has attracted much attention in drug discovery research. However, MALDI-MSI quantification (quantitative mass spectrometry imaging, QMSI) is an emerging technique, and needs to be further developed for practicable and convenient use in drug discovery research. In this study, we developed a reliable QMSI method for quantification of clozapine (antipsychotic drug) and dopamine and its metabolites in the rat brain using MALDI-MSI. An improved mimetic tissue model using powdered frozen tissue for QMSI was established as an alternative method, enabling the accurate quantification of clozapine levels in the rat brain. Furthermore, we used the improved method to evaluate drug-induced fluctuations in the concentrations of dopamine and its metabolites. This method can quantitatively evaluate drug localization in the brain and drug-induced changes in the concentration of endogenous metabolites, demonstrating the usefulness of QMSI.</p>","PeriodicalId":462,"journal":{"name":"Analytical and Bioanalytical Chemistry","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2024-08-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141911247","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-09DOI: 10.1007/s00216-024-05466-8
Tatjana Alves Soares, Barbara A Caspers, Daniel Veit, Helene M Loos
In recent decades, the compositions of preen oil and feathers have been studied to achieve insights into the chemistry of avian odours, which play a significant role in birds' social behaviour. Fewer studies are available regarding volatiles originating from other sources, such as faeces, eggs or a bird's whole body. The aims of this study were (i) to identify odour-active and further volatile compounds in zebra finch whole body odour and (ii) to semi-quantify selected volatiles and use the information to evaluate two different adsorbents for their suitability for whole body odour sampling. Volatiles from the headspace above zebra finches were sampled using an open loop system equipped with either activated charcoal or Tenax® TA. Samples were analysed by olfactory-guided approaches as well as gas chromatography-mass spectrometry. Using activated charcoal as sorbent, 26 odour-active and 73 further volatile compounds were detected, whereas with Tenax® TA 27 odour-active and 81 further volatile compounds were detected. In total, 104 compounds were (tentatively) identified, of which 22 had not been identified previously in zebra finch odour and 12 had not been described in any birds. Hints towards a chemical sex signature became evident for qualitative but not for quantitative differences. With the exception of some compounds, notably carboxylic acids and alkanes, relative peak areas obtained with the two adsorbent types were comparable. The approach described herein is proposed for future studies aiming to determine volatiles emitted by birds when, for example, parent birds are approaching the nest.
{"title":"Analytical characterization of volatiles present in the whole body odour of zebra finches.","authors":"Tatjana Alves Soares, Barbara A Caspers, Daniel Veit, Helene M Loos","doi":"10.1007/s00216-024-05466-8","DOIUrl":"https://doi.org/10.1007/s00216-024-05466-8","url":null,"abstract":"<p><p>In recent decades, the compositions of preen oil and feathers have been studied to achieve insights into the chemistry of avian odours, which play a significant role in birds' social behaviour. Fewer studies are available regarding volatiles originating from other sources, such as faeces, eggs or a bird's whole body. The aims of this study were (i) to identify odour-active and further volatile compounds in zebra finch whole body odour and (ii) to semi-quantify selected volatiles and use the information to evaluate two different adsorbents for their suitability for whole body odour sampling. Volatiles from the headspace above zebra finches were sampled using an open loop system equipped with either activated charcoal or Tenax® TA. Samples were analysed by olfactory-guided approaches as well as gas chromatography-mass spectrometry. Using activated charcoal as sorbent, 26 odour-active and 73 further volatile compounds were detected, whereas with Tenax® TA 27 odour-active and 81 further volatile compounds were detected. In total, 104 compounds were (tentatively) identified, of which 22 had not been identified previously in zebra finch odour and 12 had not been described in any birds. Hints towards a chemical sex signature became evident for qualitative but not for quantitative differences. With the exception of some compounds, notably carboxylic acids and alkanes, relative peak areas obtained with the two adsorbent types were comparable. The approach described herein is proposed for future studies aiming to determine volatiles emitted by birds when, for example, parent birds are approaching the nest.</p>","PeriodicalId":462,"journal":{"name":"Analytical and Bioanalytical Chemistry","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2024-08-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141999187","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-06DOI: 10.1007/s00216-024-05464-w
Tingting Feng, Yu Huang, Shuzhu Yan
This study introduces an innovative approach for the real-time and efficient detection of alkaline phosphatase (ALP) activity, using a calcein fluorescence probe and leveraging the static quenching properties of calcein fluorescence by Ce3+ metal ions. In this method, calcein serves as the signal element, with its fluorescence effectively preserved through energy transfer or charge transfer when coordinated with Ce3+. Conversely, ALP catalyzes the phosphopeptide substrate to generate a substantial amount of Pi, preventing calcein fluorescence quenching due to the higher affinity between Pi and Ce3+ compared with that between calcein and Ce3+. The fluorescence intensity ratio (F-F0/F0) exhibited excellent linearity, facilitating sensitive ALP detection. The proposed ALP detection method covers a range from 0 to 1.4 mU/mL (R2 = 0.9942), with the limit of detection at 0.069 mU/mL (S/N = 3). Additionally, this method was successfully applied for detecting ALP in serum samples and studying its inhibitors. This research introduces a novel clinical diagnosis approach for ALP sensing while broadening the potential applications of calcein.
本研究介绍了一种实时高效检测碱性磷酸酶(ALP)活性的创新方法,该方法利用钙黄绿素荧光探针和 Ce3+ 金属离子对钙黄绿素荧光的静态淬灭特性。在这种方法中,钙黄绿素作为信号元素,在与 Ce3+ 配位时通过能量转移或电荷转移有效地保留其荧光。相反,ALP 催化磷酸肽底物产生大量的 Pi,由于 Pi 与 Ce3+ 之间的亲和力高于钙黄绿素与 Ce3+ 之间的亲和力,从而阻止了钙黄绿素的荧光淬灭。荧光强度比(F-F0/F0)表现出良好的线性关系,有助于灵敏地检测 ALP。所提出的 ALP 检测方法的检测范围为 0 至 1.4 mU/mL(R2 = 0.9942),检测限为 0.069 mU/mL(S/N = 3)。此外,该方法还成功用于检测血清样本中的 ALP 及其抑制剂。这项研究为 ALP 检测引入了一种新的临床诊断方法,同时拓宽了钙黄绿素的潜在应用领域。
{"title":"Label-free fluorescence turn-on detection of alkaline phosphatase activity using the calcein-Ce<sup>3+</sup> complex.","authors":"Tingting Feng, Yu Huang, Shuzhu Yan","doi":"10.1007/s00216-024-05464-w","DOIUrl":"https://doi.org/10.1007/s00216-024-05464-w","url":null,"abstract":"<p><p>This study introduces an innovative approach for the real-time and efficient detection of alkaline phosphatase (ALP) activity, using a calcein fluorescence probe and leveraging the static quenching properties of calcein fluorescence by Ce<sup>3+</sup> metal ions. In this method, calcein serves as the signal element, with its fluorescence effectively preserved through energy transfer or charge transfer when coordinated with Ce<sup>3+</sup>. Conversely, ALP catalyzes the phosphopeptide substrate to generate a substantial amount of Pi, preventing calcein fluorescence quenching due to the higher affinity between Pi and Ce<sup>3+</sup> compared with that between calcein and Ce<sup>3+</sup>. The fluorescence intensity ratio (F-F<sub>0</sub>/F<sub>0</sub>) exhibited excellent linearity, facilitating sensitive ALP detection. The proposed ALP detection method covers a range from 0 to 1.4 mU/mL (R<sup>2</sup> = 0.9942), with the limit of detection at 0.069 mU/mL (S/N = 3). Additionally, this method was successfully applied for detecting ALP in serum samples and studying its inhibitors. This research introduces a novel clinical diagnosis approach for ALP sensing while broadening the potential applications of calcein.</p>","PeriodicalId":462,"journal":{"name":"Analytical and Bioanalytical Chemistry","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2024-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141896411","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-05DOI: 10.1007/s00216-024-05455-x
Ziting Gao, Jessica Lin, Wan-Chih Su, Kelly Zhang, Jason Gruenhagen, Wenwan Zhong, Yuchen Fan, Juan Bian
In recent years, the use of lipid nanoparticles (LNPs) for delivery of messenger RNA (mRNA)-based therapies has gained substantial attention in the field of drug development. In such an application, multiple LNP attributes have to be carefully characterized to ensure product safety and quality, whereas accurate and efficient characterization of these complex mRNA-LNP formulations remains a challenging endeavor. Here, we present the development and application of an online separation and characterization platform designed for the isolation and in-depth analysis of mRNAs and mRNA-loaded LNPs. Our asymmetrical flow field-flow fractionation with a multi-detector (MD-AF4) method has demonstrated exceptional resolution between mRNA-LNPs and mRNAs, delivering excellent recoveries (over 70%) for both analytes and exceptional repeatability. Notably, this platform allows for comprehensive and multi-attribute LNP characterization, including online particle sizing, morphology characterization, and determination of encapsulation efficiency, all within a single injection. Furthermore, real-time online sizing by synchronizing multi-angle light scattering (MALS) and dynamic light scattering (DLS) presented higher resolution over traditional batch-mode DLS, particularly in differentiating heterogeneous samples with a low abundance of large-sized particles. Additionally, our method proves to be a valuable tool for monitoring LNP stability under varying stress conditions. Our work introduces a robust and versatile analytical platform using MD-AF4 that not only efficiently provides multi-attribute characterizations of mRNA-LNPs but also holds promise in advancing studies related to formulation screening, quality control, and stability assessment in the evolving field of nanoparticle delivery systems for mRNAs.
{"title":"Development of an advanced separation and characterization platform for mRNA and lipid nanoparticles using multi-detector asymmetrical flow field-flow fractionation.","authors":"Ziting Gao, Jessica Lin, Wan-Chih Su, Kelly Zhang, Jason Gruenhagen, Wenwan Zhong, Yuchen Fan, Juan Bian","doi":"10.1007/s00216-024-05455-x","DOIUrl":"https://doi.org/10.1007/s00216-024-05455-x","url":null,"abstract":"<p><p>In recent years, the use of lipid nanoparticles (LNPs) for delivery of messenger RNA (mRNA)-based therapies has gained substantial attention in the field of drug development. In such an application, multiple LNP attributes have to be carefully characterized to ensure product safety and quality, whereas accurate and efficient characterization of these complex mRNA-LNP formulations remains a challenging endeavor. Here, we present the development and application of an online separation and characterization platform designed for the isolation and in-depth analysis of mRNAs and mRNA-loaded LNPs. Our asymmetrical flow field-flow fractionation with a multi-detector (MD-AF4) method has demonstrated exceptional resolution between mRNA-LNPs and mRNAs, delivering excellent recoveries (over 70%) for both analytes and exceptional repeatability. Notably, this platform allows for comprehensive and multi-attribute LNP characterization, including online particle sizing, morphology characterization, and determination of encapsulation efficiency, all within a single injection. Furthermore, real-time online sizing by synchronizing multi-angle light scattering (MALS) and dynamic light scattering (DLS) presented higher resolution over traditional batch-mode DLS, particularly in differentiating heterogeneous samples with a low abundance of large-sized particles. Additionally, our method proves to be a valuable tool for monitoring LNP stability under varying stress conditions. Our work introduces a robust and versatile analytical platform using MD-AF4 that not only efficiently provides multi-attribute characterizations of mRNA-LNPs but also holds promise in advancing studies related to formulation screening, quality control, and stability assessment in the evolving field of nanoparticle delivery systems for mRNAs.</p>","PeriodicalId":462,"journal":{"name":"Analytical and Bioanalytical Chemistry","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2024-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141888076","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-05DOI: 10.1007/s00216-024-05460-0
Cuicui Fu, Sihan Jiang, Siyu Zhuo, Jiaxin Qiu, Hualu Luo, Yan Wu, Yangyang Li, Young Mee Jung
Currently, research in the development of high-performance sensing platforms has increased to fulfill the needs of analysis and detection. In this study, we developed a novel type of surface-enhanced Raman scattering (SERS) chip composed of a covalent organic framework (COF)-silver nanoparticles (AgNPs) nanocomposite, and this nanocomposite was fabricated by a one-step method of ultrasonically mixing the obtained COF and AgNPs. The fabricated chip exhibited high sensitivity and repeatable SERS effects. Practical application results showed that the chip was highly sensitive and reliable and capable of detecting DNA bases (adenine) to fit an equation in the range from 0.01 pM to 1 nM, with an R-square of 0.97253 and a detection limit of ~0.026 pM (signal-to-noise ratio (S/N) = 3). Therefore, the proposed SERS system has potential applications in biological assays.
{"title":"Covalent organic framework-hybridized Ag nanoparticles as SERS substrate for highly sensitive detection of DNA bases.","authors":"Cuicui Fu, Sihan Jiang, Siyu Zhuo, Jiaxin Qiu, Hualu Luo, Yan Wu, Yangyang Li, Young Mee Jung","doi":"10.1007/s00216-024-05460-0","DOIUrl":"https://doi.org/10.1007/s00216-024-05460-0","url":null,"abstract":"<p><p>Currently, research in the development of high-performance sensing platforms has increased to fulfill the needs of analysis and detection. In this study, we developed a novel type of surface-enhanced Raman scattering (SERS) chip composed of a covalent organic framework (COF)-silver nanoparticles (AgNPs) nanocomposite, and this nanocomposite was fabricated by a one-step method of ultrasonically mixing the obtained COF and AgNPs. The fabricated chip exhibited high sensitivity and repeatable SERS effects. Practical application results showed that the chip was highly sensitive and reliable and capable of detecting DNA bases (adenine) to fit an equation in the range from 0.01 pM to 1 nM, with an R-square of 0.97253 and a detection limit of ~0.026 pM (signal-to-noise ratio (S/N) = 3). Therefore, the proposed SERS system has potential applications in biological assays.</p>","PeriodicalId":462,"journal":{"name":"Analytical and Bioanalytical Chemistry","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2024-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141888025","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-03DOI: 10.1007/s00216-024-05468-6
Jan P. M. Andries, Yvan Vander Heyden
In this study, a new approach for the selection of informative standardization samples from the original calibration set for the transfer of a calibration model between NIR instruments is proposed and evaluated. First, a calibration model is developed, after variable selection by the Final Complexity Adapted Models (FCAM) method, using the significance of the PLS regression coefficients (FCAM-SIG) as selection criterion. Then, the resulting model is used for the selection of the best fitting subset of calibration samples with optimally predictive ability, called the optimally predictive calibration subset (OPCS). Next, the standardization samples are selected from the OPCS. The spectra on the slave instruments are transferred to corresponding spectra on the master instrument by the widely used Piecewise Direct Standardization (PDS) method. Thereafter, for the test set on the slave instrument, a 3D response surface plot is drawn for the root mean squared error of prediction (RMSEP) as a function of the number of OPCS samples and window sizes used for the PDS method. Finally, the smallest set of calibration samples, in combination with the optimal window size, providing the optimal RMSEP, is selected as standardization set. The proposed OPCS approach for the selection of standardization samples is tested on two real-life NIR data sets providing 13 X–y combinations to model. The results show that the obtained numbers of OPCS-based standardization samples are statistically significantly lower than those obtained with the widely used representative sample selection method of Kennard and Stone, while the predictive performances are similar.