Isosbestic Research Articles

Spectroscopic Investigations of Optical Bandgap and Search for Reaction Mechanism Chemistry Due to γ-Rays Irradiated PMMA Polymer

Radiation damage and the product formation chemistry in Polymethyl methacrylate (PMMA) due to γ-irradiation have been studied by SEM, XRD, FTIR, and UV-Vis spectroscopy. Co-60 gamma source with a dose rate of 1.707 kGy/hr has been used for irradiation to a total 570 kGy dose. No significant changes in morphology upon such irradiation. Crystallinity decreases at a lower dose and then increases for a higher dose. Crosslinking dominates at lower doses, and chain scission overwhelms at higher doses in the irradiated polymer. Two isosbestic points are formed, and the absorption maxima shift towards a higher wavelength. The optical bandgap energy decreases with the addition of radiation dose. A new FTIR peak at 1638 cm-1 appeared, suggesting the formation of an unsaturation center in the irradiated polymer. Up to a dose of 409 kGy, FTIR absorption peak intensity increases and decreases with further irradiation.

New Aspects Concerning the Ampicillin Photodegradation.

New aspects concerning the photodegradation (PD) of ampicillin are reported by photoluminescence (PL), Raman scattering and FTIR spectroscopy. The exposure of ampicillin in the absence (AM) and in the presence of the excipient (AMP) to UV light leads to an intensity diminution of the photoluminescence excitation (PLE) and photoluminescence (PL) spectra and the emergence of a new IR band at 3450 cm−1. The photoluminescence studies demonstrate that the AM PD is amplified in the presence of excipients and an alkaline medium. In this last case, the PD process of AM involves the emergence of new compounds, whose presence is highlighted by: (i) the emergence of the isosbestic point at 300 nm in the UV-VIS spectra; (ii) a change in the ratio between the absorbance of IR bands situated in the spectral ranges 1200–1660 and 3250–3450 cm−1; and (iii) a change in the ratio between the intensities of the Raman lines localized in the spectral ranges 1050–1800 and 2750–3100 cm−1. A chemical mechanism of the PD processes of AM in an alkaline medium is proposed.

Multiple emerging nano-phases are at the origin of the low lattice thermal conductivity of SnSe?

Thermoelectrics are well recognized materials for energy harvesting and many solid-state cooling devices are already present on the market. SnSe is an inexpensive binary system made by earth-abundant elements that holds the record-high performance among the semiconductor materials although the origin of its ultralow thermal conductivity is still not understood. Both X-ray and neutron diffraction experiments identified in SnSe at high temperature a transition from the α-phase (Pnma) to the β-phase (Cmcm). In this contribution using for the first time in-situ temperature-dependent X-ray Absorption Fine structure spectroscopy (T-XAFS) at Sn and Se K-edge, we showed the occurrence in the XAS data of two isosbestic points, which support the coexistence of two phases in a wide temperature range. Moreover, in the SnSe matrix Sn–O bonds are continuously formed and SnO2, SeO2 and SnSe2 nanophases are emerging at high temperature. The experiment points out how these local nanophases are formed above 600 K. These emerging nano-phases affect the mean free path of phonons reducing the lattice thermal conductivity and, together with the crystal structural phase transition, may account for the low thermal conductivity measured in SnSe single crystals.

Transient absorption spectroscopy of a twisted intramolecular charge transfer (TICT) state in a DCM molecule analyzed by isosbestic points

Transient absorption spectroscopy of a twisted intramolecular charge transfer (TICT) state in a DCM molecule analyzed by isosbestic points

Austen in Amsterdam: Isotope effect in a liquid-liquid transition in supercooled aqueous solution

We investigate the H/D isotope effect in a liquid-liquid transition in crystallization-resistant supercooled aqueous solution. Using steady-state infrared spectroscopy and measuring thermal conductivities, we observe a ≈5 K shift in the onset temperature of the liquid-liquid transition, a value that is similar to the H/D isotope shifts of the HDA-LDA transition and of the Widom line of pure supercooled water [Kim et al ., Science 358 , 1589 (2017)], and that highlights the importance of isotope effects in water's supercooled regime. By employing multivariate data analysis we find isosbestic point related to the phase transformation in both isotopic systems, indicating phase coexistence during the transition. This article is dedicated to the memory of Austen Angell, and we begin with some personal memories of his two stays at the University of Amsterdam.

UV Spectrophotometric and stability indicating RP-HPLC methods for simultaneous estimation of Moxifloxacin HCl and Ketorolac tromethamine in bulk and ophthalmic dosage forms

It was the main goal of this study's research to develop simple UV-Spectrophotometric and Stability indicating RP-HPLC methods for the simultaneous estimation of Moxifloxacin HCl (MOX) and Ketorolac Tromethamine (KET) in bulk and ophthalmic dosage forms, as well as to conduct Forced Degradation experiments. When utilising linearity ranges between 1.0 and 9.0 g/ml for MOX and KET, correlation co-efficients >0.990 were used in the UV Spectrophotometry test results. Acetonitrile (40:60 v/v) was the solvent of choice. MOX and KET were discovered to have wavelengths of 295 nm and 316 nm, respectively. Researchers discovered that the isobestic point was located at 308 nm. Both medicines were separated using RP-HPLC on a SHISHEDO C18, 2504.6mm, 5 micron size column with a mobile phase made up of 40:60 v/v acetonitrile and water with flow rate of 0.9 ml/min and UV detection at 308 nm. Moxifloxacin Hcl and Ketorolac Tromethamine had retention durations of 2.080 minutes and 4.400 minutes, respectively. Moxifloxacin Hcl and Ketorolac Tromethamine have linearities of 1.0-6.0 g/ml and 1.0-6.0 g/ml, respectively. For linearity, recovery, limit of detection, and limit of quantification statistical validation was performed on the technique. Accuracy and precision were also evaluated. Analytes are well-resolved from degradation products when medicines are subjected to a variety of stresses, such as acidic or alkaline pH values, high oxidation or photo-stability temperatures, or a combination of these circumstances. The accuracy, precision, linearity, limit of detection, limit of quantification, and robustness of the two proposed techniques were effectively validated. This means that both Moxifloxacin HCl and Ketorolac Tromethamine may be estimated simultaneously in bulk and ophthalmic dose forms using these two techniques.

Determination of ionization constants for sequinidazole in aqueous solutions and mixtures of water with isopropanol, acetonitrile and ethanol

Seknidazole is a drug from the 5-nitroimidazole group with a number of side-effects. This drug is virtually unexplored from the point of view of chemico-toxicological analysis (CTA). Therefore, the development of a set of methods for the detection and quantification of secnidazole in biological fluids for use in CTA is an urgent task. Aim. To study the acid-base equilibrium of secnidazole in aqueous solutions and mixtures of water with amphiphilic solvents and determine the corresponding ionization constants. Materials and methods. Spectrophotometric measurements were performed using a SPEKOL®1500 single-beam spectrophotometer. An EV-74 ionomer was used to control the pH of the solutions. Seknidazole solutions in the concentrationof 1000 μg/ml were used in the experiment. Results and discussion. Absorption spectra of secnidazole in water and mixtures of water and amphiphilic solvents in the pH range studied showed four isobestic points characterizing two protolytic equilibria (equilibrium 1 – 240 and 295 nm, equilibrium 2 – 261 and 297 nm). The position of the isobestic points of equilibrium 2 fluctuated in the range ± 3 nm; it was due to the presence of tautomeric transformations for the molecular form of secnidazole. Conclusions. The acid-base equilibria of secnidazole in aqueous solutions and mixtures of water with amphiphilic solvents have been studied. It has been shown that in a strongly alkaline medium there is an anionic form of secnidazole R–, with further decrease in the pH value the molecular form HR appears, in a strongly acidic medium the final product – a protonated form H2R+ – is formed. The ionization constant 1 has been determined for aqueous solutions of secnidazole, mixtures of water with isopropanol, acetonitrile and ethanol. It is impossible to determine the equilibrium constant 2 by the method specified.

Different spectrophotometric methods for simultaneous quantification of lycopene and β-carotene from a binary mixture

UV-VIS spectrophotometric analysis is one of the cheapest and most handy methods used for carotenoids quantification in solutions. According to Lambert-Beer's law, carotenoids concentrations in a mixture are computed using mixture absorbances and characteristic absorption coefficients for pure compounds. This work proposes four methods for simultaneous quantification of two carotenoids using mixture spectral data, physical models of pure and mixtures spectra in acetone-hexane mixture, different wavelengths groups for absorbance of each carotenoid, the spectra overlapping property and isosbestic point presence. Two absorbance factors defined to improve the concentrations equations accuracy and different assumptions in terms of wavelengths groups and contribution of each carotenoid at mixture absorbance are considered. These methods are validated using synthetic mixtures for two carotenoids (lycopene and β-carotene) and two tomato residue extracts using equivalence test as statistical tool. IPM–II–WG6 method gives good correlation from statistical point of view, with medium accuracy errors.

Development and Validation of High Performance Thin Layer Chromatography Method for Standardization of Polyherbal Formulation Using Mangiferin and Gallic Acid as Markers

Oxitard capsules, a polyherbal formulation, is an effective natural antioxidant that prevents oxidative stress-related tissue damage and is helpful for coronary artery disease. The aim of the present work was systematic development and validation of the high-performance thin-layer chromatographic method for simultaneous quantitative estimation of mangiferin and gallic acid from oxitard capsules. Both markers, mangiferin and gallic acid were separated on a pre-coated silica gel 60 F254 thin-layer chromatographic plate, using toluene:ethyl acetate:formic acid:methanol (4:6:0.8:2 v/v/v/v) as mobile phase. The retention factor of mangiferin and gallic acid was found to be 0.28±0.03 and 0.78±0.03, respectively. The linear regression analysis data for the calibration plots of drugs scanned at isosbestic point 299 nm showed a good linear relationship with r2=0.9931 and r2=0.9901, over the concentration range of 300 to 700 ng/spot and 500 to 900 ng/spot for mangiferin and gallic acid, respectively. The validation parameter followed for simultaneous estimation of these polyherbal drugs were linearity, precision, accuracy, robustness, ruggedness and sensitivity (limit of detection and limit of quantitation). The method was found to be precise, accurate, sensitive and robust meeting all the parameters as per International Council for Harmonisation guideline Q2 (R1). Thus, the developed high-performance thin-layer chromatography method can conveniently be employed for simultaneous detection and quantification of mangiferin and gallic acid in commercial polyherbal formulation.

Analytical Validation and Stability Indicating Studies for Simultaneous Estimation of Serdexmethylphenidate and Dexmethylphenidate by RP-HPLC in Bulk and Capsules

A stability-indicating RP-HPLC method for the simultaneous determination of Serdexmethylphenidate (SER) and Dexmethylphenidate (DEX) has been developed and validated in bulk and tablet dosage forms. SER and DEX are central nervous system stimulants. This combination is used to treat attention deficit hyperactive disorder. The chromatographic analysis was carried out on a Waters C18 Column with 250mm x 4.6 and a particle size of 5 μm, using an isocratic mobile phase of Phosphate Buffer pH 4.8: Methanol (70:30, v/v) at a flow rate of 0.8 mL/min, and the eluents were monitored at an isosbestic point of 215 nm. Specificity, precision, accuracy, linearity, and robustness of the proposed method were all validated according to ICH standards. Forced degradation studies confirmed the method's stability indicating nature. SER and DEX had retention times of 2.390 and 4.602 min, respectively. The developed technique was found to be specific and accurate. SER linearity was achieved between 90-270 μg/mL, while DEX linearity was obtained between 17.50-52.50 μg/mL. SER had LOD and LOQ of 6.35 and 21.17 μg/mL, whereas DEX had LOD and LOQ of 1.18 and 3.93 μg/mL, respectively. As a result, the suggested HPLC method for the quantification of Serdexmethylphenidate (SER) and Dexmethylphenidate (DEX) was reliable, repeatable, accurate, and sensitive.

Photophysical and molecular docking approach on the interaction of water-soluble simple keto sugar with acridinedione dyes

Photophysical studies in association with molecular docking (MD) methods were employed in the determination of various molecular interactions existing between d-Fructose in the presence of a photoinduced electron transfer (PET) and non-PET based acridinedione (AD) dyes in water. Addition of fructose to AD dyes resulted in a decrease in the absorbance at the longest wavelength absorption maxima accompanied with the formation of an isosbestic point signifying a ground state complex formation. The ground state interaction between fructose and dye is presumably attributed to hydrogen-bonding (HB) and was authenticated by MD studies. Interestingly, the excited state characteristics of PET dye (ADR1) is found to be entirely different from that of non-PET dye (ADR2) on the introduction of fructose. A fluorescence quenching phenomenon is observed in PET dye, whereas an enhancement results in that of a non-PET dye. Fructose promotes electron transfer (ET) through space resulting in a decrease in the fluorescence intensity of ADR1 dye. On the contrary, it suppresses the PET process in ADR2 dye resulting in an increase in the quantum yield. Fluorescence lifetime studies of fructose with AD dyes results in a multi exponential lifetime with varying proportions. The presence of biexponential lifetime components justifies the existence of more than one distinguishable micro heterogenous environment in the aqueous phase containing unequal proportion of distribution of fructose and water molecules around the close vicinity of AD dyes. The local excited (LE) state of the fluorophore experiences a large variation in the excited state such that the emission intensity and fluorescence lifetime are governed by solute induced and solvent mediated HB interactions. MD studies further establish the existence of HB interaction of dye-fructose, wherein the dye acts as the HB donor and sugar as the acceptor. Docking techniques establishes clear and authentic information on the HB donor and acceptor sites in dye and sugar molecule resulting in a most stable conformer. The nature of interaction of a simple sugar molecule with water soluble fluorophores are explored in depth by fluorescence techniques in coordination with MD methods is imparted in the present study.

Stability indicating Rp-UPLC method development and validation for the simultaneous estimation of fosnetupitant and palonosetron in bulk and injection dosage form

A stability indicating UPLC method has been developed and validated for the simultaneous determination of fosnetupitant and palonosetron in bulk and in injection dosage form. This combination is used for the prevention of acute and delayed nausea and vomiting associated with initial and repeated courses of highly emetogenic chemotherapy for cancer. The chromatographic analysis was performed on an HSS, RP C18 column (2.1 x 100 mm, 1.8 µm) with an isocratic mobile phase composed of 0.25 M potassium dihydrogen orthophosphate buffer (pH 6.5), pH adjusted with dilute sodium hydroxide:acetonitrile (55:45 v/v), at a flow rate of 0.5 mL/min, and the eluents were monitored at an isosbestic point of 286 nm. The developed method was validated according to the ICH guidelines pertaining to specificity, precision, accuracy, linearity and robustness, and the stability indicating nature of the method was established by forced degradation studies. The retention times of fosnetupitant and palonosetron were observed at 1.390 and 2.404 min, respectively. The developed method proved to be accurate and precise. Linearity was established between 4.70 and 14.10 µg/mL for fosnetupitant and between 0.05 and 0.15 µg/mL for palonosetron. The LOD and LOQ were 0.115 and 0.385 µg/mL, respectively, for fosnetupitant, and 0.005 and 0.016 µg/mL, respectively, for palonosetron. Therefore, the proposed UPLC method was reliable, reproducible, precise and sensitive for the quantification of fosnetupitant and palonosetron.

Stability indicating reverse phase (RP)-high-performance liquid chromatography method development and validation for the simultaneous estimation of olanzapine and samidorphan in bulk and tablets

Background Patients with schizophrenia are given a combination tablet combining olanzapine (OLA), an atypical antipsychotic and samidorphan (SAM), an opioid receptor antagonist. Objectives In bulk and tablet dosage forms, a stability-indicating reverse phase (RP)-high-performance liquid chromatography technique for the simultaneous determination of OLA and SAM has been developed and validated. Materials and methods The chromatographic analysis was performed using an isocratic mobile phase of 0.1% formic acid in water : methanol : acetonitrile (10 : 40 : 50, v/v) at a flow rate of 0.8 ml/min, and the eluents were monitored at an isosbestic point of 285 nm. Results and conclusion The suggested method’s specificity, precision, accuracy, linearity, and robustness were all validated according as per International Conference on Harmonization guidelines. The method’s stability was validated by forced degradation experiments. Retention times for OLA and SAM were 2.85 and 4.79 min, respectively. The method was found to be precise and accurate. SAM linearity was found to be between 14.0 and 45.0 µg/ml, whereas OLA linearity was found to be between 22.5 and 67.5 µg/ml. The limit of detection (LOD) and limit of quantification (LOQ) of OLA were 2.65 and 8.85 µg/ml, respectively, whereas the LOD and LOQ of SAM were 8.12 and 27.06 µg/ml, respectively. As a result, the suggested high-performance liquid chromatography method for the quantification of OLA and SAM was reliable, repeatable, accurate, and sensitive.

An ESIPT-ICT steered naphthylthioic-based ionic probe with dual emissive channels exhibiting CHEF and CHEQ effects.

A naphthylthioic-based emissive probe (M) bearing a hydroxyl and amine group was designed and synthesized via a one-step Schiff base reaction process. The probe was characterized spectroscopically using 1H NMR, UV-Vis and fluorescence spectrophotometers. The probe turned out to be spectroscopically and colorimetrically selective and sensitive to multiple cations and anions. Interestingly, the probe displayed characteristics of excited-state intramolecular proton transfer (ESIPT)-driven dual emissive channels; experiencing fluorescence enhancement upon the molar additions of Al3+ as well as the anions used, events presumably ascribed to chelation fluorescence enhancement (CHEF), hydrogen bonding and deprotonation effects. Moreover, the fluorometric titration with Hg2+ resulted in ratiometric spectral behaviors of M, with the disappearance of the peak at 450 nm, concomitant with the appearance of a new peak at 520 nm, distinguished by a clear isosbestic point, the same behaviors exhibited by Sn2+ and Ag+ analytes towards M. The introduction of all other cations used, resulted in fluorescence quenching, attributable to chelation enhanced fluorescence quenching (CHEQ), thereby inhibiting the ESIPT process. The experiments were all carried out in the aqueous environment medium of DMSO-H2O (9 : 1) at ambient temperature. Theoretical density functional theory calculations were carried out to gain insight into the interaction of M with cations and anions, and their influence on the HOMO-LUMO energy gaps.

The Photochemical Chlorate-Iodide Clock Reaction.

Mixing iodide and perchloric acid solutions with an excess of chlorate inside a diode-array spectrophotometer led to the observation of an abrupt decrease of the absorbance at the 215 nm isosbestic point after an induction period. The clock time decreases by increasing the initial concentrations of chlorate and acid, but increasing the initial iodide concentration has an opposite effect. The proposed mechanism simulates the experimental results and considers the interaction of UV light with iodide, producing iodine and triiodide ion. The autocatalytic core of this mechanism is the same as that employed to explain the autocatalytic behavior of chlorine dioxide-iodine reaction, but considering H2IO+ as the reactive species rather than HOI, being a more realistic mechanism for acid conditions.

HOCH2CH2NH2 – TROPEOLIN OOO – H2O SYSTEM ACID-BASIC PROPERTIES IN THE PRESENCE OF HCl, HClO4, H2SO4 AND SO2H2O

The influence of hydrochloric, chloric, sulfuric and sulfurous acids (HCl, HClO4, H2SO4 and SO2×H2O, respectively) on protolytic equilibria in the system monoethanolamine (MEA) – tropeolin OOO (TrOOO) – water (CMEA = 0.1 M; pH = 1.0 ÷ 9.5) was studied by pH-metric, spectrophotometric and colorimetric methods. The acid-base behavior of the HOCH2CH2NH2 – TrOOO – H2O system was investigated at CTrOOO = 1,12 ×10-4 М, CMEA = 1,0×10-4 ÷ 1,0 М (pH = 8,25 ÷ 12,05), T = 293 K. TrOOO in this system exists in two tautomeric forms due to acid-base dissociation of the 4-OH group and associates formed by H-bonding with MEA molecules. There is a direct ratio between the pH values ​​of solutions and the total color difference (ΔE76), in contrast to the specific color difference (SCD). The difference in the behavior of the H2SO4 – HOCH2CH2NH2 – TrOOO – H2O system from the systems with HCl and HClO4 is due to the fact that the interaction of the first acid with MEA (8,0 £ pH) forms an ionic associate [HOCH2СH2NH3]2(SO4), which is more stable than ionic pairs [[HOCH2СH2NH3](HSO4), [HOCH2СH2NH3](ClO4), [HOCH2СH2NH3]Cl и [HOCH2СH2NH3](O3S-C­10H6-N=N-C6H4-SO3)[H3NCH2СH2OH]. Acid-base dissociation constants in systems significantly depend on the structure and physicochemical parameters of the mineral acid. In the electronic absorption spectra of the SO2 – MEA – TrOOO – H2O system (pH £ 7,5), there is a pronounced isobestic point at 415 nm, due to the dynamic equilibrium between ion-molecular forms. The coincidence of the maxima on the curves ΔE76 = f(pH) and SCD = f(pH) for the indicated system, in contrast to others studied in this work, was stated. The difference between the spectrophotometric and colorimetric behavior of the SO2 – MEA – TrOOO – H2O system from behavior of the systems with HCl, HClO4, and H2SO4 systems is due to the sulfur(IV)oxyanions with an azo indicator redox interaction.

VALIDATED NOVEL SPECTROSCOPIC METHOD FOR ESTIMATION OF TRIAMCINOLONE ACETONIDE IN NASAL SPRAY

A simple, sensitive, accurate, precise and cost-effective pH independent spectrophotometric method has been developed for the estimation of triamcinolone acetonide in nasal sprays. Estimation was carried out at the isosbestic point of drug solutions, Isosbestic point was measured by scanning equimolar solution of triamcinolone acetonide separately in phosphate buffer pH 3.0, phosphate buffer pH 7.0 and phosphate buffer pH 10.0 at a concentration of 10 µg mL-1. They were scanned in the wavelength range of 200-400 nm. The isosbestic point was found to be 230.0 nm in acidic, basic and neutral condition; hence pH independent wavelength 230 nm was used for estimation of triamcinolone acetonide. The method observed linear response in the concentration range of 3-18 µg mL-1 at 230 nm. Developed method has been validated in accordance with ICH guideline Q2 R1 for several parameters like linearity, precision, accuracy, limit of detection and limit of quantification. The developed and validated analytical method was successfully applied to the estimation of triamcinolone acetonide in marketed nasal spray formulations.

Exploration of Self-Aggregation of Coumarin 7 and Coumarin 30 in Water: Role of β-Cyclodextrin as a Modulator.

Steady-state and time-resolved spectroscopic studies demonstrate that two members of the coumarin class of dyes, coumarin 7 (C7) and coumarin 30 (C30), undergo self-aggregation in water. The development of hypsochromically shifted new absorption bands in addition to the existing monomer bands with an increase in concentration of the dyes in an aqueous medium suggests that the aggregates are of H-type. An absorption-based kinetic study reveals that the rate of aggregation of C30 is an order of magnitude faster than that of C7. Second-order rate kinetics, as obtained from the half-life (t1/2) data, implies that the aggregates are dimeric in nature. Observations of isosbestic points in area-normalized absorption spectra (ANAS) and isoemissive points in area-normalized fluorescence excitation spectra (ANFES) and time-resolved area-normalized emission spectra (TRANES) establish that ground-state monomer ⇌ dimer equilibria for both of the systems are preserved in the photoexcited state. The present study further establishes that β-cyclodextrin is the most efficient of the three common cyclodextrins in shifting the equilibria toward the monomer by encapsulating the monomers within its cavity, making β-CD a convenient modulator to control the self-aggregation process. Dynamic light scattering (DLS), quantum chemical calculations, and molecular docking studies provide further support to our propositions.

Simultaneous estimation of recently FDA approved co-formulated ophthalmic solution benoxinate and fluorescein: Application to aqueous humor

Nine simple, cost-effective, and sensitive spectrophotometric methods were developed to simultaneously assay benoxinate HCl and fluorescein sodium in their co-formulated eye drops without barring common excipients. A direct UV spectrophotometric method (method I) was developed for their FLU assay at 481 nm over the concentration range of 0.6–10.0 μg mL−1. Meanwhile, BEN was assayed over the concentration range of 1.0–25.0 μg mL−1 by different UV based methods, namely, conventional dual-wavelength method (DW) (method II), first derivative1D spectrophotometry (method III), second derivative2D spectrophotometry (method IV), ratio spectra difference spectrophotometry (method V), the first derivative of ratio spectra (method VI), ratio subtraction method (method VII), isosbestic point method (ISP) (method VIII) and absorption factor method (method IX). The performance of the proposed methods was assessed relying on the correlation coefficients, relative standard deviations, and limits of detection and quantitation. The variance ratio F-test and Student t-test showed no significant differences between the obtained results of the developed methods and those of reference methods. The proposed methods were also applied to determine studied drugs in commercial eye drops and aqueous humor.

Multispectral optoacoustic tomography for non-invasive disease phenotyping in pediatric spinal muscular atrophy patients

Proximal spinal muscular atrophy (SMA) is a rare progressive, life limiting genetic motor neuron disease. While promising causal therapies are available, meaningful prognostic biomarkers for therapeutic monitoring are missing. We demonstrate handheld Multispectral Optoacoustic Tomography (MSOT) as a novel non-invasive imaging approach to visualize and quantify muscle wasting in pediatric SMA. While MSOT signals were distributed homogeneously in muscles of healthy volunteers (HVs), SMA patients showed moth-eaten optoacoustic signal patterns. Further signal quantification revealed greatest differences between groups at the isosbestic point for hemoglobin (SWL 800 nm). The SWL 800 nm signal intensities further correlated with clinical phenotype tested by standard motor outcome measures. Therefore, handheld MSOT could enable non-invasive assessment of disease burden in SMA patients.