Isotopomeric Peak Assignment for N2O in Cross-Labeling Experiments by Fiber-Enhanced Raman Multigas Spectroscopy.

Human intervention in nature, especially fertilization, greatly increased the amount of N2O emission. While nitrogen fertilizer is used to improve nitrogen availability and thus plant growth, one negative side effect is the increased emission of N2O. Successful regulation and optimization strategies require detailed knowledge of the processes producing N2O in soil. Nitrification and denitrification, the main processes responsible for N2O emissions, can be differentiated using isotopic analysis of N2O. The interplay between these processes is complex, and studies to unravel the different contributions require isotopic cross-labeling and analytical techniques that enable tracking of the labeled compounds. Fiber-enhanced Raman spectroscopy (FERS) was exploited for sensitive quantification of N2O isotopomers alongside N2, O2, and CO2 in multigas compositions and in cross-labeling experiments. FERS enabled the selective and sensitive detection of specific molecular vibrations that could be assigned to various isotopomer peaks. The isotopomers 14N15N16O (2177 cm-1) and 15N14N16O (2202 cm-1) could be clearly distinguished, allowing site-specific measurements. Also, isotopomers containing different oxygen isotopes, such as 14N14N17O, 14N14N18O, 15N15N16O, and 15N14N18O could be identified. A cross-labeling showed the capability of FERS to disentangle the contributions of nitrification and denitrification to the total N2O fluxes while quantifying the total sample headspace composition. Overall, the presented results indicate the potential of FERS for isotopic studies of N2O, which could provide a deeper understanding of the different pathways of the nitrogen cycle.

Spectrally Resolved and Highly Parallelized Raman Difference Spectroscopy for the Analysis of Drug-Target Interactions between the Antimalarial Drug Chloroquine and Hematin.

Malaria is a severe disease caused by cytozoic parasites of the genus Plasmodium, which infiltrate and infect red blood cells. Several drugs have been developed to combat the devastating effects of malaria. Antimalarials based on quinolines inhibit the crystallization of hematin into hemozoin within the parasite, ultimately leading to its demise. Despite the frequent use of these agents, there are unanswered questions about their mechanisms of action. In the present study, the quinoline chloroquine and its interaction with the target structure hematin was investigated using an advanced, highly parallelized Raman difference spectroscopy (RDS) setup. Simultaneous recording of the spectra of hematin and chloroquine mixtures with varying compositions enabled the observation of changes in peak heights and positions based on the altered molecular structure resulting from their interaction. A shift of (-1.12 ± 0.05) cm-1 was observed in the core-size marker band ν(CαCm)asym peak position of the 1:1 chloroquine-hematin mixture compared to pure hematin. The oxidation-state marker band ν(pyrrole half-ring)sym exhibited a shift by (+0.93 ± 0.13) cm-1. These results were supported by density functional theory (DFT) calculations, indicating a hydrogen bond between the quinolinyl moiety of chloroquine and the oxygen atom of ferric protoporphyrin IX hydroxide (Fe(III)PPIX-OH). The consequence is a reduced electron density within the porphyrin moiety and an increase in its core size. This hypothesis provided further insights into the mechanism of hemozoin inhibition, suggesting chloroquine binding to the monomeric form of hematin, thereby preventing its further crystallization to hemozoin.

Comprehensive multi-gas study by means of fiber-enhanced Raman spectroscopy for the investigation of nitrogen cycle processes.

The extensive use of synthetic fertilizers has led to a considerable increase in reactive nitrogen input into agricultural and natural systems, resulting in negative effects in multiple ecosystems, the so-called nitrogen cascade. Since the global population relies on fertilization for food production, synthetic fertilizer use needs to be optimized by balancing crop yield and reactive nitrogen losses. Fiber-enhanced Raman spectroscopy (FERS) is introduced as a unique method for the simultaneous quantification of multiple gases to the study processes related to the nitrogen cycle. By monitoring changes in the headspace gas concentrations, processes such as denitrification, nitrification, respiration, and nitrogen fixation, as well as fertilizer addition were studied. The differences in concentration between the ambient and prepared process samples were evident in the Raman spectra, allowing for differentiation of process-specific spectra. Gas mixture concentrations were quantified within a range of low ppm to 100% for the gases N2, O2, CO2, N2O, and NH3. Compositional changes were attributed to processes of the nitrogen cycle. With help of multivariate curve resolution, it was possible to quantify N2O and CO2 simultaneously. The impact of fertilizers on N-cycle processes in soil was simulated and analyzed for identifying active processes. Thus, FERS was proven to be a suitable technique to optimize fertilizer composition and to quantify N2O and NH3 emissions, all with a single device and without further sample preparation.

Molecular Interactions Identified by Two-Dimensional Analysis-Detailed Insight into the Molecular Interactions of the Antimalarial Artesunate with the Target Structure ß-Hematin by Means of 2D Raman Correlation Spectroscopy.

A thorough understanding of the interaction of endoperoxide antimalarial agents with their biological target structures is of utmost importance for the tailored design of future efficient antimalarials. Detailed insights into molecular interactions between artesunate and ß-hematin were derived with a combination of resonance Raman spectroscopy, two-dimensional correlation analysis, and density functional theory calculations. Resonance Raman spectroscopy with three distinct laser wavelengths enabled the specific excitation of different chromophore parts of ß-hematin. The resonance Raman spectra of the artesunate-ß-hematin complexes were thoroughly analyzed with the help of high-resolution and highly sensitive two-dimensional correlation spectroscopy. Spectral changes in the peak properties were found with increasing artesunate concentration. Changes in the low-frequency, morphology-sensitive Raman bands indicated a loss in crystallinity of the drug-target complexes. Differences in the high-wavenumber region were assigned to increased distortions of the planarity of the structure of the target molecule due to the appearance of various coexisting alkylation species. Evidence for the appearance of high-valent ferryl-oxo species could be observed with the help of differences in the peak properties of oxidation-state sensitive Raman modes. To support those findings, the relaxed ground-state structures of ten possible covalent mono- and di-meso(Cm)-alkylated hematin-dihydroartemisinyl complexes were calculated using density functional theory. A very good agreement with the experimental peak properties was achieved, and the out-of-plane displacements along the lowest-frequency normal coordinates were investigated by normal coordinate structural decomposition analysis. The strongest changes in all data were observed in vibrations with a high participation of Cm-parts of ß-hematin.

Investigations on the Novel Antimalarial Ferroquine in Biomimetic Solutions Using Deep UV Resonance Raman Spectroscopy and Density Functional Theory.

Deep ultraviolet (DUV) resonance Raman experiments are performed, investigating the novel, promising antimalarial ferroquine (FQ). Two buffered aqueous solutions with pH values of 5.13 and 7.00 are used, simulating the acidic and neutral conditions inside a parasite's digestive vacuole and cytosol, respectively. To imitate the different polarities of the membranes and interior, the buffer's 1,4-dioxane content was increased. These experimental conditions should mimic the transport of the drug inside malaria-infected erythrocytes through parasitophorous membranes. Supporting density functional theory (DFT) calculations on the drug's micro-speciation were performed, which could be nicely assigned to shifts in the peak positions of resonantly enhanced high-wavenumber Raman signals at λexc = 257 nm. FQ is fully protonated in polar mixtures like the host interior and the parasite's cytoplasm or digestive vacuole (DV) and is only present as a free base in nonpolar ones, such as the host's and parasitophorous membranes. Additionally, the limit of detection (LoD) of FQ at vacuolic pH values was determined using DUV excitation wavelengths at 244 and 257 nm. By applying the resonant laser line at λexc = 257 nm, a minimal FQ concentration of 3.1 µM was detected, whereas the pre-resonant excitation wavelength 244 nm provides an LoD of 6.9 µM. These values were all up to one order of magnitude lower than the concentration found for the food vacuole of a parasitized erythrocyte.

Towards therapeutic drug monitoring of antibiotic levels - analyzing the pharmacokinetics of levofloxacin using DUV-resonance Raman spectroscopy.

Therapeutic drug monitoring (TDM) plays an important role in clinical practice. Here, pharmacokinetics has a decisive influence on the effective antibiotic concentration during treatment. Moreover, different kinetics exist for different administration forms. Accordingly, adjusting the correct concentration depends, in addition to gender, age, weight, clinical picture, etc., on the dosage form of the antibiotic. This study investigates the capability of deep UV resonance Raman spectroscopy (DUV-RRS) to simulate the pharmacokinetics of fluoroquinolone levofloxacin after two different administration forms (intravenous and oral). Three different pre-processing methods were applied, and the best agreement with the simulation was achieved using the extended multiplicative scatter correction. The resulting spectra were used for partial least squares (PLS) regression and ordinary least squares (OLS) regression. The kinetic parameters were compared with the simulated data, with PLS showing the best performance for intravenous administration and a comparable result to OLS for oral administration, while the errors are smaller. The acquired results show the potential of DUV-RRS in combination with PLS regression as a promising supportive method for TDM.

Parallelized Raman Difference Spectroscopy for the Investigation of Chemical Interactions.

Raman spectroscopy provides an extremely high chemical selectivity. Raman difference spectroscopy is a technique to reveal even the smallest differences that occur due to weak interactions between substances and changes in the molecular structure. To enable parallelized and highly sensitive Raman difference spectroscopy in a microtiter-array, a diffractive optical element, a lens array, and a fiber bundle were integrated into a Raman spectroscopy setup in a unique fashion. The setup was evaluated with a microtiter-array containing pyridine-water complexes, and subwavenumber changes below the spectrometer's resolution could be resolved. The spectral changes were emphasized with two-dimensional correlation analysis. Density functional theory calculation and "atoms in molecule" analysis were performed to simulate the intermolecular long-range interactions between water and pyridine molecules and to get insight into the involved noncovalent interactions, respectively. It was found that by the addition of pyridine, the energy portion of hydrogen bonds to the total complexation energy between pyridine and water reduces. These results demonstrate the unique abilities of the new setup to investigate subtle changes due to biochemically important molecular interactions and opens new avenues to perform drug binding assays and to monitor highly parallelized chemical reactions.

Activity and electron donor preference of two denitrifying bacterial strains identified by Raman gas spectroscopy.

Human activities have greatly increased the input of reactive nitrogen species into the environment and disturbed the balance of the global N cycle. This imbalance may be offset by bacterial denitrification, an important process in maintaining the ecological balance of nitrogen. However, our understanding of the activity of mixotrophic denitrifying bacteria is not complete, as most research has focused on heterotrophic denitrification. The aim of this study was to investigate substrate preferences for two mixotrophic denitrifying bacterial strains, Acidovorax delafieldii and Hydrogenophaga taeniospiralis, under heterotrophic, autotrophic or mixotrophic conditions. This complex analysis was achieved by simultaneous identification and quantification of H2, O2, CO2, 14N2, 15N2 and 15N2O in course of the denitrification process with help of cavity-enhanced Raman spectroscopic (CERS) multi-gas analysis. To disentangle electron donor preferences for both bacterial strains, microcosm-based incubation experiments under varying substrate conditions were conducted. We found that Acidovorax delafieldii preferentially performed heterotrophic denitrification in the mixotrophic sub-experiments, while Hydrogenophaga taeniospiralis preferred autotrophic denitrification in the mixotrophic incubation. These observations were supported by stoichiometric calculations. The results demonstrate the prowess of advanced Raman multi-gas analysis to study substrate use and electron donor preferences in denitrification, based on the comprehensive quantification of complex microbial gas exchange processes.

Hydrogen and C2-C6 Alkane Sensing in Complex Fuel Gas Mixtures with Fiber-Enhanced Raman Spectroscopy.

Power-to-gas is a heavily discussed option to store surplus electricity from renewable sources. Part of the generated hydrogen could be fed into the gas grid and lead to fluctuations in the composition of the fuel gas. Consequently, both operators of transmission networks and end users would need to frequently monitor the gas to ensure safety as well as optimal and stable operation. Currently, gas chromatography-based analysis methods are the state of the art. However, these methods have several downsides for time-resolved and distributed application and Raman gas spectroscopy is favorable for future point-of-use monitoring. Here, we demonstrate that fiber-enhanced Raman gas spectroscopy (FERS) enables the simultaneous detection of all relevant gases, from major (methane, CH4; hydrogen, H2) to minor (C2-C6 alkanes) fuel gas components. The characteristic peaks of H2 (585 cm-1), CH4 (2917 cm-1), isopentane (765 cm-1), i-butane (798 cm-1), n-butane (830 cm-1), n-pentane (840 cm-1), propane (869 cm-1), ethane (993 cm-1), and n-hexane (1038 cm-1) are well resolved in the broadband spectra acquired with a compact spectrometer. The fiber enhancement achieved in a hollow-core antiresonant fiber enables highly sensitive measurements with limits of detection between 90 and 180 ppm for different hydrocarbons. Both methane and hydrogen were quantified with high accuracy with average relative errors of 1.1% for CH4 and 1.5% for H2 over a wide concentration range. These results show that FERS is ideally suited for comprehensive fuel gas analysis in a future, where regenerative sources lead to fluctuations in the composition of gas.

Fiber-Enhanced Raman Gas Spectroscopy for the Study of Microbial Methanogenesis.

Microbial methanogenesis is a key biogeochemical process in the carbon cycle that is responsible for 70% of global emissions of the potent greenhouse gas methane (CH4). Further knowledge about microbial methanogenesis is crucial to mitigate emissions, increase climate model accuracy, or advance methanogenic biogas production. The current understanding of the substrate use of methanogenic microbes is limited, especially regarding the methylotrophic pathway. Here, we present fiber-enhanced Raman spectroscopy (FERS) of headspace gases as an alternate tool to study methanogenesis and substrate use in particular. The optical technique is nondestructive and sensitive to CH4, hydrogen (H2), and carbon dioxide with a large dynamic range from trace levels (demonstrated LoDs: CH4, 3 ppm; H2, 49 ppm) to pure gases. In addition, the portable FERS system can provide quantitative information about methanol concentration in the liquid phase of microbial cultures through headspace gas sampling (LoD 25 ppm). We demonstrate how FERS gas sensing could enable us to track substrate and product levels of microbial methanogenesis with just one instrument. The versatility of Raman gas spectroscopy could moreover help us to elucidate links between nitrogen and carbon cycle in microbial communities in the near future.

Rapid Raman Spectroscopic Analysis of Stress Induced Degradation of the Pharmaceutical Drug Tetracycline.

Stress factors caused by inadequate storage can induce the unwanted degradation of active compounds in pharmaceutical formulations. Resonance Raman spectroscopy is presented as an analytical tool for rapid monitoring of small concentration changes of tetracycline and the metabolite 4-epianhydrotetracycline. These degradation processes were experimentally induced by changes in temperature, humidity, and irradiation with visible light over a time period of up to 23 days. The excitation wavelength λexc = 413 nm was proven to provide short acquisition times for the simultaneous Raman spectroscopic detection of the degradation of tetracycline and production of its impurity in small sample volumes. Small concentration changes could be detected (down to 1.4% for tetracycline and 0.3% for 4-epianhydrotetracycline), which shows the potential of resonance Raman spectroscopy for analyzing the decomposition of pharmaceutical products.

Fiber-Enhanced Raman Gas Spectroscopy for 18O-13C-Labeling Experiments.

Stable isotopes are used in ecology to track and disentangle different processes and pathways. Especially for studies focused on the gas exchange of plants, sensing techniques that offer oxygen (O2) and carbon dioxide (CO2) sensitivity with isotopic discrimination are highly sought after. Addressing this challenge, fiber-enhanced Raman gas spectroscopy is introduced as a fast optical technique directly combining 13CO2 and 12CO2 as well as 18O2 and 16O2 measurements in one instrument. We demonstrate how a new type of optical hollow-core fiber, the so-called revolver fiber, is utilized for enhanced Raman gas sensing. Carbon dioxide and oxygen isotopologues were measured at concentrations expected when using 13C- and 18O-labeled gases in plant experiments. Limits of detection have been determined to be 25 ppm for CO2 and 150 ppm for O2. The combination of measurements with different integration times allows the creation of highly resolved broadband spectra. With the help of calculations based on density functional theory, the line at 1512 cm-1 occurring in the oxygen spectrum is assigned to 18O16O. The relative abundances of the isotopologues 18O16O and nitrogen 15N14N were in good agreement with typical values. For CO2, fiber-enhanced Raman spectra show the Fermi diad and hotbands of 12C16O2, 13C16O2, and 12C18O16O. Several weak lines were observed, and the line at 1426 cm-1 was identified as originating from the (0 4 0 2) → (0 2 0 2) transition of 12C16O2. With the demonstrated sensitivity and discriminatory power, fiber-enhanced Raman spectroscopy is a possible alternative means to investigate plant metabolism, directly combining 13CO2 and 12CO2 measurements with 18O2 and 16O2 measurements in one instrument. The presented method thus has large potential for basic analytical investigations as well as for applications in the environmental sciences.

Characterization of fuel gases with fiber-enhanced Raman spectroscopy.

Common gaseous fuels are mixtures of several components. As the properties of the fuels can vary with the composition, but combustion needs to be stable, reliable analytical methods are highly sought after. Raman spectroscopic methods have proved their suitability for the characterization of diverse gaseous mixtures. They have the potential to overcome existing limitations of established technologies, since they are fast, non-consumptive, and accurate. Here, we demonstrate a gas sensor based on fiber-enhanced Raman spectroscopy (FERS) for fuel gas monitoring. Online detection of all gas components, including alkanes, carbon dioxide (CO2), nitrogen (N2), and hydrogen sulfide (H2S), for varying concentration ranges from tens of vol% down to the ppm level enables a comprehensive characterization of the fuels. The developed sensor system features a pinhole assembly which sufficiently reduces the background signal from the fiber to enable the detection of C2-C4 alkanes occurring in low concentrations. Detection limits in the low ppm region were achieved for the minor components of fuel gases, which allow the online monitoring of necessary purification steps, e.g., for biogas. The obtained results indicate that fiber-enhanced Raman sensors have the potential for comprehensive online and onsite gas sensing for fuel gas quality control. Graphical abstract.

Highly Sensitive Detection of the Antibiotic Ciprofloxacin by Means of Fiber Enhanced Raman Spectroscopy.

Sepsis and septic shock exhibit a rapid course and a high fatality rate. Antibiotic treatment is time-critical and precise knowledge of the antibiotic concentration during the patients' treatment would allow individual dose adaption. Over- and underdosing will increase the antimicrobial efficacy and reduce toxicity. We demonstrated that fiber enhanced Raman spectroscopy (FERS) can be used to detect very low concentrations of ciprofloxacin in clinically relevant doses, down to 1.5 µM. Fiber enhancement was achieved in bandgap shifted photonic crystal fibers. The high linearity between the Raman signals and the drug concentrations allows a robust calibration for drug quantification. The needed sample volume was very low (0.58 µL) and an acquisition time of 30 s allowed the rapid monitoring of ciprofloxacin levels in a less invasive way than conventional techniques. These results demonstrate that FERS has a high potential for clinical in-situ monitoring of ciprofloxacin levels.

Fiber-Array-Based Raman Hyperspectral Imaging for Simultaneous, Chemically-Selective Monitoring of Particle Size and Shape of Active Ingredients in Analgesic Tablets.

The particle shape, size and distribution of active pharmaceutical ingredients (API) are relevant quality indicators of pharmaceutical tablets due to their high impact on the manufacturing process. Furthermore, the bioavailability of the APIs from the dosage form depends largely on these characteristics. Routinely, particle size and shape are only analyzed in the powder form, without regard to the effect of the formulation procedure on the particle characteristics. The monitoring of these parameters improves the understanding of the process; therefore, higher quality and better control over the biopharmaceutical profile can be ensured. A new fiber-array-based Raman hyperspectral imaging technique is presented for direct simultaneous in-situ monitoring of three different active pharmaceutical ingredients- acetylsalicylic acid, acetaminophen and caffeine- in analgesic tablets. This novel method enables a chemically selective, noninvasive assessment of the distribution of the active ingredients down to 1 µm spatial resolution. The occurrence of spherical and needle-like particles, as well as agglomerations and the respective particle size ranges, were rapidly determined for two commercially available analgesic tablet types. Subtle differences were observed in comparison between these two tablets. Higher amounts of acetaminophen were visible, more needle-shaped and bigger acetylsalicylic acid particles, and a higher incidence of bigger agglomerations were found in one of the analgesic tablets.

Counterfeit and Substandard Test of the Antimalarial Tablet Riamet® by Means of Raman Hyperspectral Multicomponent Analysis.

The fight against counterfeit pharmaceuticals is a global issue of utmost importance, as failed medication results in millions of deaths every year. Particularly affected are antimalarial tablets. A very important issue is the identification of substandard tablets that do not contain the nominal amounts of the active pharmaceutical ingredient (API), and the differentiation between genuine products and products without any active ingredient or with a false active ingredient. This work presents a novel approach based on fiber-array based Raman hyperspectral imaging to qualify and quantify the antimalarial APIs lumefantrine and artemether directly and non-invasively in a tablet in a time-efficient way. The investigations were carried out with the antimalarial tablet Riamet® and self-made model tablets, which were used as examples of counterfeits and substandard. Partial least-squares regression modeling and density functional theory calculations were carried out for quantification of lumefantrine and artemether and for spectral band assignment. The most prominent differentiating vibrational signatures of the APIs were presented.

Fiber-Enhanced Raman Sensing of Cefuroxime in Human Urine.

Fiber-enhanced Raman spectroscopy was developed for the chemically selective and sensitive quantification of the important antibiotic cefuroxime in human urine. A novel optical sensor fiber was drawn and precisely prepared. In this fiber structure, light is strongly confined in the selectively filled liquid core, and the Raman scattered signal is collected with unprecedented efficiency over an extended interaction length. The filling, emptying, and robustness are highly improved due to the large core size (>30 µm). Broadband step-index guidance allows the free choice of the most suitable excitation wavelength in complex body fluids. The limit of detection of cefuroxime in human urine was improved by 2 orders of magnitude (to µM level). The quantification of cefuroxime was achieved in urine after oral administration. This method has great potential for the point-of-care monitoring of antibiotics concentrations and is an important step forward to enable clinicians to rapidly adjust doses.

Monitoring of gas composition in a laboratory biogas plant using cavity enhanced Raman spectroscopy.

Biogas production from organic raw materials is a highly complex biotechnological process. The responsible anaerobic fermentation process is difficult to measure due to its multi-stage nature. Still, optimization of biogas production and the development of robust and efficient process management strategies require continually updated information about the process. Hence, the development of a comprehensive sensor system with high temporal resolution is key to further advancement in biogas technology. Here, we demonstrate a gas sensor based on cavity enhanced Raman spectroscopy for biogas monitoring. Online detection of all gas components of a biogas mixture enables a comprehensive quantification. In addition, robust calibration routines facilitate the adaptation of the sensor for biogas monitoring. A simulated concentration course of a typical fermentation process with defined gas mixtures consisting of CH4, CO2, N2, O2 and H2 showed reliable results for all relevant biogas components for varying concentration ranges from ppm to 100 vol%. The response time of 5 seconds allows online detection and - as a consequence - real time information is obtained about the biogas composition. A laboratory biogas reactor was designed to operate biogas production on a miniaturized scale and analyze it using the Raman gas sensor. The developed sensor enables the observation of methane production throughout the first 24 h of the fermentation process. The obtained results show the suitability of cavity enhanced Raman spectroscopy as a gas sensor to monitor the entire process of biogas production. As this strategy would allow the process to be manipulated and optimized according to the current state, it is of great biotechnological interest.

Analysis of Fiber-Enhanced Raman Gas Sensing Based on Raman Chemical Imaging.

Fiber enhanced Raman spectroscopy (FERS) is an arising new technique for versatile highly sensitive and selective multigas analysis in various applications, such as environmental monitoring and medical breath diagnosis. In this study, the performance of FERS was thoroughly studied with the help of a specially designed multichannel Raman chemical imaging. Several types of hollow core photonic crystal fibers were thoroughly analyzed in terms of their performance in light confinement and sensitive gas sensing. The optimal fiber length for Raman gas sensing was found to be 15 cm in our spectroscopic system. To separate the Raman scattering of the target gas molecules from the background generated by the silica microstructure of the fiber, the optimal diameter of a spatial filter was analyzed and quantified as Ø3.9 µm, which balances the suppression of the silica background and the attenuation of the gas signal, originating from different regions in the plane of the fiber end-face. To achieve an easy-to-use gas monitoring system with stable performance, an automated coupling-method was developed, to simplify the alignment of the FERS setup. The optimized design of the FERS setup has remarkable potential for highly sensitive, miniaturized, easy-to-use, and versatile gas sensing.

Ultrasensitive Detection of Antiseptic Antibiotics in Aqueous Media and Human Urine Using Deep UV Resonance Raman Spectroscopy.

Deep UV resonance Raman spectroscopy is introduced as an analytical tool for ultrasensitive analysis of antibiotics used for empirical treatment of patients with sepsis and septic shock, that is, moxifloxacin, meropenem, and piperacillin in aqueous solution and human urine. By employing the resonant excitation wavelengths λexc = 244 nm and λexc = 257 nm, only a small sample volume and short acquisition times are needed. For a better characterization of the matrix urine, the main ingredients were investigated. The capability of detecting the antibiotics in clinically relevant concentrations in aqueous media (LODs: 13.0 ± 1.4 µM for moxifloxacin, 43.6 ± 10.7 µM for meropenem, and 7.1 ± 0.6 µM for piperacillin) and in urine (LODs: 36.6 ± 11.0 µM for moxifloxacin, and 114.8 ± 3.1 µM for piperacillin) points toward the potential of UV Raman spectroscopy as point-of-care method for therapeutic drug monitoring (TDM). This procedure enables physicians to achieve fast adequate dosing of antibiotics to improve the outcome of patients with sepsis.