Comparing silver and gold nanoislands' surface plasmon resonance for bisacodyl and its metabolite quantification in human plasma.

Gold and silver nanoparticles have witnessed increased scientific interest due to their colourful colloidal solutions and exceptional applications. Comparing the localized surface plasmon resonance (LSPR) of gold and silver nanoparticles is crucial for understanding and optimizing their optical properties. This comparison informs the design of highly sensitive plasmonic sensors, aids in selecting the most suitable nanoparticles for applications like surface-enhanced infrared spectroscopy (SEIRA) and biomedical imaging, and guides the choice between gold and silver nanoparticles based on their catalytic and photothermal properties. Ultimately, the study of LSPR facilitates the tailored use of these nanoparticles in diverse scientific and technological applications. Two SEIRA methods combined with partial least squares regression (PLSR) chemometric tools were developed. This development is based on the synthesis of homogeneous, high-dense deposited metal nanoparticle islands over the surface of glass substrates to be used as lab-on-chip SEIRA sensors for the determination of bisacodyl (BIS) and its active metabolite in plasma. SEM micrographs revealed the formation of metallic islands of colloidal citrate-capped gold and silver nanoparticles of average sizes of 29.7 and 15 nm, respectively. BIS and its active metabolite were placed on the nanoparticles' coated substrates to be directly measured, then PLSR chemometric modelling was used for the quantitative determinations. Plasmonic citrate-capped gold nanoparticle substrates showed better performance than those prepared using citrate-capped silver nanoparticles in terms of preparation time, enhancement factor, PLSR model prediction, and quantitative results. This study offers a way to determine BIS and its active metabolite in the concentration range 15-240 ng/mL in human plasma using inexpensive disposable glass-coated substrates that can be prepared in 1 h to get results in seconds with good recovery between 98.77 and 100.64%. The sensors provided fast, simple, selective, molecular-specific and inexpensive procedures to determine molecules in their pure form and biological fluid.

A Green-and-White Integrative Analytical Strategy Combining Univariate and Chemometric Techniques for Quantifying Recently Approved Multi-Drug Eye Solution and Potentially Cancer-Causing Impurities: Application to the Aqueous Humor.

BACKGROUND: Drug impurities are now seen as a major threat to the production of pharmaceuticals around the world and a major part of the global contamination problem, especially when it comes to carcinogenic impurities. OBJECTIVE: We present the first spectrophotometric strategy based on a combination of univariate and multivariate methods as impurity profiling methods for the estimation of lignocaine (LIG) and fluorescein (FLS) with their carcinogenic impurities: 2,6-xylidine (XYL) and benzene-1,3-diol (BZD). METHOD: The data processing strategy depends on overcoming unresolved bands by employing five affordable, accurate, selective, and sensitive methods. The methods applied were a direct UV univariate spectrophotometric analysis (D0) and four multivariate chemometric methods, including classical least squares (CLS), principal component regression (PCR), partial least squares (PLS), and genetic algorithm (GA-PLS). FLS analysis (1-16 µg/mL) was performed using the D0 method at 478 nm; then, the application of the ratio subtraction method (RSM) allowed the removal of interference caused by the FLS spectrum. From the resulting ratio spectra, LIG, XYL, and BZD can be efficiently determined by chemometrics. The calibration set was carefully selected at five concentration levels using a partial factorial training design, resulting in 25 mixtures with central levels of 160, 40, and 3 µg/mL for LIG, XYL, and BZD, respectively. Another 13 samples were applied to validate the predictive ability. RESULTS: The statistical parameters demonstrated exceptional recoveries and smaller prediction errors, confirming the experimental model's predictive power. CONCLUSIONS: The proposed approach was effectively tested using newly FDA-approved LIG and FLS pharmaceutical preparation and aqueous humor. Additionally, it was effectively assessed for whiteness, greenness, and sustainability using five assessment tools. HIGHLIGHTS: With its remarkable analytical performance, sustainability, affordability, simplicity, and cost-efficiency, the proposed strategy is an indispensable tool for quality control and in situ analysis in little-equipped laboratories, increasing the proposed approach's surveillance ability.

Environmentally sustainable DRS-FTIR probe assisted by chemometric tools for quality control analysis of cinnarizine and piracetam having diverged concentration ranges: Validation, greenness, and whiteness studies.

A novel diffuse reflectance fourier transform infrared spectroscopic method accompanied by chemometrics was optimized to fulfill the white analytical chemistry and green analytical chemistry principles for the quantification of cinnarizine and piracetam for the first time without any prior separation in their challenging pharmaceutical preparation, which has a pretty substantial difference in the concentration of cinnarizine/piracetam (1:16). Furthermore, the suggested method was used for cinnarizine/piracetam dissolution testing as an effective alternative to traditional methods. For the cinnarizine/piracetam dissolution tests, we used a dissolution vessel with 900 mL of phosphate buffer pH 2.5 at 37 °C ± 0.5 °C, then the sampling was carried out by frequent withdrawal of 20 µl samples from the dissolution vessel at a one-minute interval, over one hour, then representative fourier transform infrared spectra were recorded. To create a partial-least-squares regression model, a fractional factorial design with 5 different levels and 2 factors was used. This led to the creation of 25 mixtures, 15 as a calibration set and 10 as a validation set, with varying concentration ranges: 1-75 and 16-1000 µg/mL for cinnarizine/piracetam, respectively. Upon optimization of the partial-least-squares regression model, in terms of latent variables and spectral region, root mean square error of cross-validation of 0.477 and 0.270, for cinnarizine/piracetam respectively, were obtained. The optimized partial-least-squares regression model was further validated, providing good results in terms of recovery% (around 98 to 102 %), root mean square error of prediction (0.436 and 3.329), relative root mean square error of prediction (1.210 and 1.245), bias-corrected mean square error of prediction (0.059 and 0.081), and limit of detection (0.125 and 2.786) for cinnarizine/piracetam respectively. Ultimately, the developed method was assessed for whiteness, greenness, and sustainability using five assessment tools. the developed method achieved a greener national environmental method index and complementary green analytical procedure index quadrants with higher eco-scale assessment scores (91), analytical greenness metric scores (0.87), and red-greenblue 12 algorithm scores (89.7) than the reported methods, showing high practical and environmental acceptance for quality control of cinnarizine/piracetam.

An innovative nanoparticle-modified carbon paste sensor for ultrasensitive detection of lignocaine and its extremely carcinogenic metabolite residues in bovine food samples: Application of NEMI, ESA, AGREE, ComplexGAPI, and RGB12 algorithms.

Nowadays, veterinary medicine residues have been viewed as a major threat to food safety worldwide, especially when dealing with carcinogenic residues. Herein, we present the first differential pulse voltammetric method for the quantification of lignocaine and its carcinogenic metabolite 2,6-xylidine residues in bovine food samples, aided by five greenness and whiteness assessment tools, including NEMI, ESA, ComplexGAPI, AGREE, and RGB12. The method depends on the electrochemical oxidation after modification of the carbon paste sensor with recycled Al2O3-NPs functionalized multi-walled carbon nanoparticles. The produced sensor (Al2O3-NPs/MWCNTs/CPE) was characterized using XRD, FT-IR, EDX, SEM, and TEM. As expected, the active surface area and electron transfer processes were accelerated by the modification, resulting in ultra-sensitive quantification with detection limits of 19.00 and 13.94 nM for lignocaine and 2,6-xylidine, respectively. In terms of greenness, whiteness, sustainability, analytical effectiveness, and economic and practical considerations, the proposed method outperforms the reported methods.

Underivatized Amino Acid Chromatographic Separation: Optimized Conditions for HPLC-UV Simultaneous Quantification of Isoleucine, Leucine, Lysine, Threonine, Histidine, Valine, Methionine, Phenylalanine, Tryptophan, and Tyrosine in Dietary Supplements.

Amino acids (AAs) are considered as the building blocks of life. Unlike nonessential AAs, the human body cannot synthesize essential AAs and should be supplied in food or dietary supplements. The aim of the work is simultaneous HPLC-UV determination of 10 structurally related AAs without pre- or postderivatization in powdered dietary supplements (PDSs). This was challenging, especially because PDS has no standardized procedures for its quality control. HPLC-UV chromatograms of the 10 AAs were recorded using a gradient elution of the mobile phase on a CLC-C18 column at 225 nm. The elution started with 100% of phosphate buffer (pH 7.4, 10 mM) for 10 min; then, the concentration of acetonitrile increased linearly to reach 50% for another 15 min at room temperature. Good separation was achieved within a 25 min run time without pre- or postderivatization. The method was carefully validated according to the ICH guidelines over the linearity range of 100-200, 50-200, 20-150, 50-400, 20-250, 75-175, 50-250, 50-250, 50-300, and 5-100 µg/mL for l-lysine, l-threonine, l-histidine, l-valine, l-methionine, l-isoleucine, l-leucine, l-tyrosine, l-phenylalanine, and l-tryptophan, respectively, with mean recoveries ranges between 98.91 and 100.77. The method was found to be precise, and the relative standard deviation (RSD) was found to be between 0.28 and 1.92 with recoveries between 97.91 and 101.11. The method was found to be robust that resists deliberate changes in pH, flow rate, and mobile-phase percentages. It was successfully applied for the analysis of PDSs. The proposed method could be very useful for the quality control of the 10 structurally related AAs during their synthesis and for testing raw materials and pharmaceutical preparations.

Identification of milk quality and adulteration by surface-enhanced infrared absorption spectroscopy coupled to artificial neural networks using citrate-capped silver nanoislands.

Milk is one of the most important multicomponent superfoods owing to its rich macronutrient composition. It requires quality control at all the production stages from the farm to the finished products. A localized surface plasmon resonance optical sensor based on a citrate-capped silver nanoparticle (Cit-AgNP)-coated glass substrate was developed. The fabrication of such sensors involved a single-step synthesis of Cit-AgNPs followed by surface modification of glass slides to be coated with the nanoparticles. The scanning electron microscope micrographs demonstrated that the nanoparticles formed monolayer islands on glass slides. The developed surface-enhanced infrared absorption spectroscopy (SEIRA) sensor was coupled to artificial neural networking (ANN) for the qualitative differentiation between cow, camel, goat, buffalo, and infants' formula powdered milk types. Moreover, it can be used for the quantitative determination of the main milk components such as fat, casein, urea, and lactose in each milk type. The qualitative results showed that the obtained FTIR spectra of cow and buffalo milk have high similarity, whereas camel milk resembled infant formula powdered milk. The most difference in FTIR characteristics was evidenced in the case of goat milk. The developed sensor adds several advantages over the traditional techniques of milk analysis using MilkoScan™ such as less generated waste, elimination of pre-treatment steps, minimal sample volume, low operation time, and on-site analysis.

Innovative electrochemical electrode modified with Al2O3 nanoparticle decorated MWCNTs for ultra-trace determination of tamsulosin and solifenacin in human plasma and urine samples and their pharmaceutical dosage form.

A simple, cheap, sensitive, and time-saving square wave voltammetric (SWV) procedure using a carbon paste electrode modified with aluminum oxide nanoparticle decorated multi-walled carbon nanoparticles (Al2O3-NPs/MWCNTs/CPE) is presented for the ultra-sensitive determination of tamsulosin (TAM) and solifenacin (SOL), one of the most prescribed pharmaceutical combinations in urology. Characterization of the developed electrode was performed using scanning electron microscopy (SEM), X-ray diffraction (XRD) patterns, energy dispersive X-ray analysis (EDX), transmission electron microscopy (TEM) and FT-IR spectrophotometry. The voltammetric behavior of TAM/SOL was evaluated using Al2O3-NPs in different content and electrode compositions. The use of Al2O3 functionalized MWCNTs as a CPE modifier increased the process of electron transfer as well as improved the electrode active surface area therefore, ultra-sensitive results were acquired with a linear range of 10-100 and 12-125 ng ml-1 for TAM and SOL respectively, and a limit of the detection value of 2.69 and 3.25 ng ml-1 for TAM and SOL, respectively. Interestingly, the proposed method succeeded in quantifying TAM and SOL with acceptable percentage recoveries in dosage forms having diverged concentration ranges and in the biological fluids with very low peak plasma concentration (C max). Furthermore, the proposed method was validated, according to the ICH criteria, and shown to be accurate and reproducible.

A New Chemometrically Assisted UV Spectrophotometric Method for Simultaneous Determination of Tamsulosin and Dutasteride in Their Pharmaceutical Mixture.

BACKGROUND: Tamsulosin (TAM) and dutasteride (DUT) are ranked among the most frequently prescribed therapies in urology. Interestingly, studies have also been carried out on TAM/DUT in terms of their ability to protect against recent COVID-19. However, very few studies were reported for their simultaneous quantification in their combined dosage form and were mainly based on chromatographic analysis. Subsequently, it is very important to offer a simple, selective, sensitive, and rapid method for the quantification of TAM and DUT in their challenging dosage form. OBJECTIVE: In this study, a new chemometrically assisted ultraviolet (UV) spectrophotometric method has been presented for the quantification of TAM and DUT without any prior separation. METHOD: For the calibration set, a partial factorial experimental design was used, resulting in 25 mixtures with central levels of 20 and 25 µg/mL for TAM and DUT, respectively. In addition, to assess the predictive ability of the developed approaches, another central composite design of 13 samples was used as a validation set. Post-processing by chemometric analysis of the recorded zero-order UV spectra of these sets has been applied. These chemometric approaches include partial least-squares (PLS) and genetic algorithm (GA), as an effective variable selection technique, coupled with PLS. RESULTS: The models' validation criteria displayed excellent recoveries and lower errors of prediction. CONCLUSIONS: The proposed models were effectively used to determine TAM/DUT in their combined dosage form, and statistical comparison with the reported method revealed satisfactory results. HIGHLIGHTS: Overall, this work presents powerful simple, selective, sensitive, and precise methods for simultaneous quantification of TAM/DUT in their dosage form with satisfactory results. The predictive ability and accuracy of the developed methods offer the opportunity to be employed as a quality control technique for the routine analysis of TAM/DUT when chromatographic instruments are not available.

The Potential Synergistic Activity of Zolmitriptan Combined in New Self-Nanoemulsifying Drug Delivery Systems: ATR-FTIR Real-Time Fast Dissolution Monitoring and Pharmacodynamic Assessment.

PURPOSE: The current work aimed to overcome the poor permeability and undesirable adverse effects of Zolmitriptan (ZMT) and to increase its efficacy in the treatment of acute migraine by exploiting the synergistic effect of the essential oil, lavender, to fabricate ZMT self-nanoemulsifying drug delivery systems (ZMT-SNEDDS). METHODS: ZMT-SNEDDS were fabricated based on full factorial design (32) to statistically assess the impact of oil and surfactant concentrations on the nanoemulsion globule size, zeta potential and percentage drug dissolution efficiency. An ATR-FTIR method was developed and validated for continuous real-time monitoring of ZMT dissolution and permeation. The dose of the optimized ZMT-SNEDDS used in the efficacy study was selected according to the acute toxicity study. The efficacy study was performed on migraineous rats induced by nitroglycerin and was evaluated by the activity cage and thermal tests, electroencephalogram, electroconvulsive stimulation, and biochemical analysis of brain tissue. Finally, histopathological and immunohistochemical examinations of the cerebra were carried out. RESULTS: Upon dilution, the optimized ZMT-SNEDDS (F5) exhibited nanosized spherical droplets of 19.59±0.17 nm with narrow size distribution, zeta potential (-23.5±1.17mV) and rapid emulsification characteristics. ATR-FTIR spectra elucidated the complete time course of dissolution and permeation, confirming F5 superior performance. Moreover, ZMT-SNEDDS (F5) showed safety in an acute toxicity study. ZMT concentration in rat brain tissues derived from F5 was lower compared to that of ZMT solution, yet its effect was better on the psychological state, algesia, as well as maintaining normal brain electrical activity and delayed convulsions. It counteracted the cerebral biochemical alternations induced by nitroglycerin, which was confirmed by histopathological examination. CONCLUSION: In a nutshell, these findings corroborated the remarkable synergistic efficacy and the high potency of lavender oil-based ZMT-SNEDDS in migraine management compared to the traditional zolmitriptan solution.

Optimization of localized surface plasmon resonance hot spots in surface-enhanced infrared absorption spectroscopy aluminum substrate as an optical sensor coupled to chemometric tools for the purity assay of quinary mixtures.

Surface-enhanced infrared absorption spectroscopy offers an alternative to conventional IR spectroscopy and utilizes the signal enhancement exerted by the plasmon resonance of nanostructured metal thin films. Citrate-capped silver nanoparticles were prepared in a single-step method, and their morphology was identified using transmission electron microscopy, scanning electron microscopy, ultraviolet/visible spectrophotometry, and Zetasizer. The nanoparticles generated were deposited on the surface of cheap aluminum slides for different durations aiming for the selection of the best time producing a thin film, suitable to act as a lab-on-a-chip SEIRA substrate. These substrates were coupled to partial least squares regression tools for simultaneous resolving of the quinary mixture in commercial dosage forms of bisoprolol, perindopril, bisoprolol acid degradation product, bisoprolol alkali degradation product, and perindoprilat in concentration ranges of 15-75, 60-300, 15-55, 12-60, and 20-80 µg/mL with limits of detection values of 0.69, 3.43, 0.97, 1.25, and 1.09 µg/mL, respectively. Overall, we could demostrate that the localized surface plasmon resonance sensor coupled to chemometrics provides cheap, simple, selective, multiplex, rapid, and molecular specific procedures for impurity detection, which would be beneficial in many applications for quality control and quality accuracy of active pharmaceutical ingredients.

Widening the applications of the Just-Dip-It approach: a solid contact screen-printed ion-selective electrode for the real-time assessment of pharmaceutical dissolution testing in comparison to off-line HPLC analysis.

Over past years, the field of pharmaceutical dissolution testing has significantly expanded to cover not only the quality control of dosage forms, but also to play an important role in the bioavailability testing paradigm and screening of most formulations. These tests usually need a very long time sampling and monitoring, so that the automation of sampling is laborsaving. Problems often occur with these automatic devices due to sampling lines that may disconnect, crimp, carry over, become mixed up, or are inadequately cleaned. Potentiometric sensors, such as liquid contact (LC-ISE) or solid contact ion-selective electrodes (SC-SP-ISE), can provide timely data to be used for the real-time tracking of the amount of active pharmaceutical ingredients (APIs) released in the dissolution medium without these problems. In this work, we adopted the Just-Dip-It approach as a process analytical technology solution with the ultimate goal of advancing the ion selective sensors to their most effective use in pharmaceutical analysis. Two sensors were fabricated, the traditional LC-ISE and SC-SP-ISE. The sensing poly-vinyl chloride membranes of two electrodes were prepared using 2-nitrophenyl octyl ether as a plasticizer to soften the membrane, and the reduction in resistance to pioglitazone ions (PIO) permeability was achieved through the incorporation of sodium tetraphenylborate and calix[8]arene as a cationic exchanger salt and inclusion complexing ligand, respectively. Finally, prepared membranes were turned into the flexible perm-selective slices of hydrophobic plastic, which work as a barrier to other compounds, except for the PIO cation in the concentration range of 1 × 10-6 to 1 × 10-2 M and 1 × 10-5 to 1 × 10-2 M for SC-SP-ISE and LC-ISE, respectively. The challenges and opportunities of both sensors in comparison to a developed HPLC method were discussed for the dissolution testing of the combination dosage forms of pioglitazone. Potentiometric methods were validated according to IUPAC guidelines, while HPLC was validated according to ICH guidelines to ensure accuracy and precision.

FTIR combined with chemometric tools (fingerprinting spectroscopy) in comparison to HPLC: which strategy offers more opportunities as a green analytical chemistry technique for pharmaceutical analysis.

Fourier transform infrared spectroscopy (FTIR) is a widespread technique that can provide a chemical signature (fingerprints) of solid, liquid, or gas samples with a wide range of analytical applications. High-performance liquid chromatography (HPLC) is a leading analytical strategy for pharmaceutical analysis. Here we present a side-by-side comparison of the potential of these techniques for quantitative analysis of pharmaceutical active ingredient combinations in light of green analytical chemistry (GAC) principles. The methods were successfully applied for the analysis of ketoprofen (KTP)/hyoscine (HYS) and benzocaine (BENZ)/dextromethorphan HBr (DEX) in their binary mixtures and pharmaceutical preparations. In FTIR analysis, calibration models were constructed based on partial least squares regression (PLSR) with satisfactory regression coefficients (r2) of 0.9998, 0.9994, 0.9855, and 0.9895 for KTP, HYS, DEX, and BENZ, respectively, over a wide linearity range (10-100, 10-100, 5-75, and 10-100 µg mL-1) that covers the concentration ratios in the market samples. External validation using a validation set and internal validation using leave-one-out-cross-validation calculations were performed, and small root-mean-square-error-of-cross-validation (RMSECV) values were obtained indicating the good resolving power of the models. The same performance was obtained using the HPLC method for separation of the same mixtures with r2 equal to 0.9998, 0.9999, 0.9998, and 0.9998 over linear ranges of 50-1000, 10-200, 5-100, and 5-100 µg mL-1 for KTP, HYS, DEX, and BENZ, respectively. The HPLC methods were validated following ICH guidelines with good recovery percentages in the range of 98-100%. The statistical comparison of the FTIR and HPLC methods for analysis showed almost the same results with good applicability towards commercial dosage forms. Concerning the twelve GAC principles, a detailed comparison was performed to highlight the opportunities of each technique. FTIR-PLSR analysis showed superior performance as it allows for less solvent consumption, portability, less generated waste, short operating time, less operation cost, less energy consumption, and more operator safety and it is easily coupled with chemometric tools. Besides, FTIR is a direct analytical technique that can be used for the analysis of samples in all the physical forms (solid, liquid, and gas) without modifications.

Indirect Nano-sensing approach: A universal potentiometric silver ion selective sensor for inline quantitative profiling of the kinetics and thermodynamics of formation and decay of silver nanoparticles.

Indirect Nano-sensing are indispensable chemical sensory points that make use of the unique properties of nanoparticles to derive information about it to our macroscopic world. Precious Silver nanoparticles have become more attractive in many areas of healthcare and life sciences leading to massive industrial production and increase of environmental exposure which may lead to Nanotoxicity accompanied by the release of Ag+ ions. A reversible silver selective screen-printed electrode was fabricated, optimized, and validated. A wide linearity range of 1 × 10-6 - 1 × 10-2 M was obtained, with a LOD that reaches 1.5 × 10-7 M and a typical slope of monovalent cationic compounds of 59.6 mV/decade. It showed high selectivity towards the cationic Ag+ ion activity in presence of the negatively charged citrate capped silver nanoparticles (Cit-AgNPs). The fabricated sensor has been used for tracking the decrease of Ag+ activity during the reduction of AgNO3 with tri-sodium citrate during the Bottom-up synthesis of Cit-AgNPs at different temperature (60, 70 and 80 °C). The kinetic parameters (Activation energy (Ea) and Reaction rate (K)) and the thermodynamic characteristics (free activation energy (ΔG), entropy (ΔS), enthalpy (ΔH)) have been calculated. Furthermore, it has been used for tracking the release of Ag+ during the spontaneous and stimulated decay of Cit-AgNPs. The present work could be a junction between nanotechnology and recent advances in design of a reproducible, portable real-time analyzer for in-process monitoring of the production of Cit-AgNPs and its environmental hazards with many advantages in comparison to the reported techniques in terms of portability, simplicity, cost-efficient, fast inline tracking, no sampling, real-time profiles at high temperatures and it does not need professional operators.

Surface enhanced infrared absorption spectroscopy (SEIRA) as a green analytical chemistry approach: Coating of recycled aluminum TLC sheets with citrate capped silver nanoparticles for chemometric quantitative analysis of ternary mixtures as a green alternative to the traditional methods.

The past two decades have seen the full expansion of all fields of Nanotechnology, Chemometrics, Recycling, and Vibration spectroscopy into most of the research areas. The proposed method involves the harmonization of the previously mentioned fields as a vital tool to fulfill the concepts of sustainability and green analytical chemistry. This may reduce the negative impact of analytical laboratory activities on the surrounding environment and enables the implementation of sustainable development principles to analytical laboratories. This work compares the performance of surface enhanced infrared spectroscopy (SEIRA) with traditional chromatographic techniques for quantification of active pharmaceutical ingredients concerning the twelve principles of green analytical chemistry. The used aluminum TLC slides were recycled to be used as a SEIRA substrate. Citrate capped silver nanoparticles were synthesized via one step chemical reduction method, characterized, and deposited on the surface of the recycled aluminum TLC slides to be used as an active mid-infrared surface for quantification of the active pharmaceutical ingredient's combinations. SEIRA coupled with PLSR chemometric tool was developed, validated and successfully applied to mixtures having diverged concentration ranges (5, 30 and 500 µg ml-1) of Pholcodine, Pseudoephedrine and Paracetamol, respectively. Pholcodine is a synthetic or semi-synthetic opium alkaloid that derived from morphine. Pseudoephedrine is a sympathomimetic agent that is prohibited in sports competitions by the world antidoping agency at certain concentration levels. Paracetamol has analgesic and antipyretic actions. After optimization of the method parameters and number of latent factors, a good linear calibration model of the PLSR strategy was obtained as indicated by the lowest root mean square error of calibration and prediction obtained and the regression coefficients R2 of 0.9912, 0.9888, and 0.9992, respectively. The calibration ranges for the three drugs in their pharmaceutical combinations was 2.5-12.5, 15-75 and 200-600 µg ml-1, respectively. The method showed high resolving power for the three drugs in presence of excipients and good recoveries were obtained in a range of 97-102% with relative standard deviation < 2. The developed lab on a chip SEIRA analyzer in comparison to the traditional chromatographic techniques does not only fulfill the twelve principles of GAC but also it combines the merits of high throughput straightforward fingerprint analyzers, portable to measure samples on its place, cost effective, reduced sample volume and solvent consumption, coupled with intelligent chemometric tools to analyze multiple samples, reduced trials and time to get results.

Chemical fingerprinting and quantitative monitoring of the doping drugs bambuterol and terbutaline in human urine samples using ATR-FTIR coupled with a PLSR chemometric tool.

The use of performance-enhancing drugs is prohibited in sports competitions according to the World Anti-Doping Agency (WADA) regulations. Here, ATR-FTIR spectroscopy coupled with a partial least squares regression (PLSR) chemometric tool was used for the detection of the misuse of such substances. Bambuterol and its metabolite terbutaline have been included in the list of prohibited doping agents. Therefore, we used bambuterol and terbutaline as models for the accurate and simultaneous qualitative and quantitative analysis of bambuterol and terbutaline in human urine samples. The method was straightforward and once the urine samples were collected, they could be directly applied to the surface of the ZnSe prism (ATR unit) to get the results within one minute. A calibration set with a partial factorial design was used to develop the PLSR model that could be used to predict the concentration of unknown samples containing the two drugs. The developed method was carefully validated and successfully applied to the urine sample analysis of human volunteers. The drugs were quantified at nanogram level concentrations. A side-by-side comparison of the proposed method with the routine GC-MS method was performed to demonstrate the challenges and opportunities of each method.

Correction: Chemical fingerprinting and quantitative monitoring of the doping drugs bambuterol and terbutaline in human urine samples using ATR-FTIR coupled with a PLSR chemometric tool.

[This corrects the article DOI: 10.1039/C9RA10033D.].

Attenuated Total Reflectance Fourier Transformation Infrared spectroscopy fingerprinted online monitoring of the kinetics of circulating Butyrylcholinesterase enzyme during metabolism of bambuterol.

We have described a continuous flow ATR-FTIR method for measuring some of the Butyrylcholinesterase enzyme kinetics (Km and Vmax). This is done by developing a circulating system to be close as much as possible to the human circulation using human serum as a source of the enzyme with adjusted pH, isotonicity and temperature to give the maximum affinity of the enzyme towards its substrate (bambuterol). The experiment was running continuously for 90 min to monitor the production of terbutaline from the zero time of its appearance with a measured spectrum in each minute using ZnSe prism. The method was selective and successful for determination of Vmax to be 8.16 × 10-8 mol/min/ml and Km to be 2.28 × 10-5 mol, showing high affinity of the enzyme towards its prodrug substrate Bambuterol. This study critically probes the quantitative ability of the ATR-FTIR method for terbutaline, which was validated according to ICH guidelines showing high accuracy 100.39% and high selectivity towards the produced terbutaline, as the produced spectrums considered as fingerprint of each compound.