Search

Nitric oxide (NO) is one of the reactive nitrogen species (RNS) that has been proposed to be a key signaling molecule in migraine. Migraine is a neurological disorder that is linked to irregular NO levels, which necessitates precise NO quantification for effective diagnosis and treatment. This work introduces a novel fluorescent probe, 2,3-diaminonaphthelene-1,4-dione (DAND), which was designed and synthesized to selectively detect NO in-vitro and in-vivo as a migraine biomarker. DAND boasts high aqueous solubility, biocompatibility, and facile synthesis, which enable highly selective and sensitive detection of NO under physiological conditions. NO reacts with diamine moieties (recognition sites) of DAND, results in the formation of a highly fluorescent product (DAND-NO) known as 1H-naphtho[2,3-d][1,2,3]triazole-4,9-dione at λ em 450 nm. The fluorescence turn-on sensing mechanism operates through an intramolecular charge transfer (ICT) mechanism. To maximize fluorescence signal intensity, parameters including DAND concentration, reaction temperature, reaction time and pH were systematically optimized for sensitive and precise NO determination. The enhanced detection capability (LOD = 0.08 μmol L -1 ) and high selectivity of the probe make it a promising tool for NO detection in brain tissue homogenates. This demonstrates the potential diagnostic value of the probe for individuals suffering from migraine. Furthermore, this study sheds light on the potential role of zolmitriptan (ZOLM), an antimigraine medication, in modulating NO levels in the brain of rats with nitroglycerin-induced migraine, emphasizing its significant impact on reducing NO levels. The obtained results could have significant implications for understanding how ZOLM affects NO levels and may aid in the development of more targeted and effective migraine treatment strategies., Competing Interests: Declaration of competing interest The current study is new, original and not under consideration elsewhere. The authors declare no conflict of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Antimigraine combination therapy has shown significant effectiveness in relieving pain, as well as reducing the frequency, duration, and severity of migraine attacks if compared to a single migraine medication. This work represents the first analytical investigation for emphasizing the synergistic effect of combining ophthalmic beta blockers with triptans in migraine treatment. The presented study was conducted to investigate the pharmacokinetic profile of almotriptan (ALM), a serotonin (5-HT 1B/1D ) receptor agonist used to treat migraine, when coadministered with timolol (TIM) or verapamil (VER) which are considered as an adjuvant therapy in migraine prevention. Ion pair chromatography (IPC) with online fluorescence detection was applied to simultaneously detect and quantify the binary mixtures of ALM/TIM and ALM/VER in rabbit plasma samples. The separation was achieved using a Platinum C 18 analytical column with a mobile phase composed of methanol: 35 mmol L -1 phosphate buffer solution containing 10 mmol L -1 SDS at pH = 6.8 (60:40 v/v). Several parameters were evaluated during the optimization of separation conditions including mobile phase composition, buffer concentration, buffer pH and concentration of ion pair reagent. A thorough investigation of the retention mechanism was performed, and the results showed that Coulomb forces were the main contributors to the overall retention mechanism, which may be hydrophobically assisted. QuEChERS extraction technique was utilized to extract the investigated drugs from plasma samples and a detailed study was carried out to optimize partition/extraction solvents, pH, extraction salts, sample volume and clean-up step. The method had a limit of detection and quantitation of 5.6 and 16.9 ng mL -1 for ALM in ALM/TIM mixture and 2.5 and 7.6 ng mL -1 for ALM in ALM/VER mixture, with an overall recovery not less than 95.22%. This newly proposed method offers a faster alternative to existing chromatographic methods for extraction and determination of ALM in binary mixtures with TIM or VER in rabbit plasma and provides a platform for studying pharmacokinetic parameters. The coadministration of either TIM or VER with ALM resulted in a notable rise in C max (maximum plasma concentration) and AUC (area under the plasma concentration-time curve) of ALM, implying possible alterations in the absorption and overall exposure of ALM., Competing Interests: Declaration of Competing Interest The current study is new and original and not under consideration elsewhere. The authors declare no conflict of interest., (Copyright © 2023 Elsevier B.V. All rights reserved.)

In this work, a fast, versatile, and convenient dispersive solid-phase micro-extraction (DSPME) method is combined with a spectro-densitometric technique for the analysis of zolmitriptan (ZOLM) in biological fluids. Fe 3 O 4 /FeOOH magnetic nanocomposites (MNCs) were prepared by a co-precipitation method in aqueous solutions and utilized subsequently as a sorbent in DSPME. By coupling DSPME with high-performance thin-layer chromatography (HPTLC) with fluorescence detection, the preconcentration and determination of (ZOLM) in presence of metoclopramide (MET) and paracetamol (PARA), which are prescribed as an adjuvant therapy with ZOLM, was accomplished. Adsorption capability was assessed using both Langmuir and Freundlich adsorption isotherm models. The adsorption data was fitted to Langmuir adsorption isotherm model as reflected by high determination coefficient (R 2  = 0.9944). Moreover, adsorption kinetics was assessed by pseudo-first and pseudo-second order kinetic models. The data was fitted to pseudo-second order kinetics, which proves that ZOLM interaction with the adsorbent is a chemisorption process. Surface complexation with MNCs was suggested to explain the pH dependence of ZOLM sorption. The key parameters of extraction and desorption steps (including pH, extraction time, sample volume, magnetic adsorbent amount, and desorption circumstances) were evaluated. Optimized conditions for solid phase microextraction of ZOLM were pH 2.9, 5.0 mg Fe 3 O 4 /FeOOH MNCs, 15 min vortex-assisted extraction time and 3 × 200 μL of methanol: 33% ammonia; 4:1 as eluent. The analysis was achieved using ACN: dichloromethane: 33% ammonia (22.5: 6.0: 1.5, v/v/v) as a mobile phase and the fluorescence detection was carried out at 223 nm. The proposed DSPME method was successfully applied for trace quantification of ZOLM in rabbits' plasma (n = 6) after oral administration with a linearity range of 50.0 - 400.0 ng mL -1 (R 2  = 0.9931), a detection limit of 12.0 ng mL -1 and extraction recovery of 97.27-99.89% with an RSD < 2% (n = 9). Moreover, the selectivity of the proposed approach for analysis of ZOLM in the presence of MET and PARA is demonstrated., Competing Interests: Declaration of Competing Interest The current study is new and original and not under consideration elsewhere. The authors declare no conflict of interest., (Copyright © 2021 Elsevier B.V. All rights reserved.)

A rapid, sensitive and selective flow injection analysis (FIA) method was developed for the determination of some selective α1-blockers including; terazosin (TER), doxazosin (DOX), prazosin (PRZ), and alfuzosin (ALF). The method was based on enhancement of the native fluorescence of the studied drugs in the presence of sodium dodecyl sulfate (SDS). The method was optimized for the buffer type, concentration and pH, surfactant type and concentration, flow rate and detection wavelengths in order to achieve the maximum sensitivity. The results showed that the best sensitivity was obtained by using SDS (10 mM) in phosphate buffer (20 mM, pH = 3), flow rate was 0.5 ml/min and the detector was set at λex = 250 and λem = 389. Under these optimum conditions there was a linear relationship between the concentration and the fluorescence intensity in the range from 5-400 ng ml(-) with correlation coefficient of more than 0.998. The detection and quantitation limits for the studied drugs by the proposed method were 3.2-11.9 ng ml(-1) and 10.8-39.7 ng ml(-1), respectively. The method was validated in accordance with the requirements of ICH guidelines and shown to be suitable for intended applications. Moreover, the binding constants for α1-blockers -SDS system were determined using the adduct model. The proposed method has been applied successfully for the analysis of the pure forms for studied drugs and also their pharmaceutical formulations and the results were compared with official methods.