Mahmoud El-Tantawy

Abstract The advent of a new pharmaceutical formulation evokes the need for examining the chemical stability of their constituents and establishing proper stability-indicating methods. Herein, the stability of the newly co-formulated Tamsulosin and Tadalafil were examined under different stress conditions. The acidic degradation of Tamsulosin yielded its sulfonated derivative, while Tadalafil was susceptible to both acidic and basic degradation. Two stability-indicating chromatographic methods, namely; high-performance thin-layer chromatography and high-performance liquid chromatography, have been developed. Significant high-performance thin-layer chromatography-fractionation could be achieved by utilizing a stationary phase of silica gel 60 F254 and a mobile phase composed of ethyl acetate/toluene/methanol/ammonia (4:2:4:0.6, by volumes) with densitometric recording at 280 nm over a concentration range of 0.5?25 ?g/band for both drugs. The HPLC-separation could be reached on XBridge? C18 column isocraticaly by using a mobile phase having acetonitrile/phosphate buffer, pH 6.0 (45:55, v/v) pumped at a flow rate of 1.7 mL/min and applying diode array ultraviolet-detection at 210 nm over a linearity range of 3?70 ?g/mL for each drug. Specificity of the two methods was additionally assured via peak purity assessment. Moreover, the methods were distinctly exploited for evaluating the drugs? stability in accelerated stability-studied samples of Tamplus? capsules.

Stability-indicating reversed-phase high-performance liquid chromatography (RP-HPLC) and normal-phase high-performance thin-layer chromatography (NP-HPTLC) methods have been developed for the determination of palonosetron which is a potent antiemetic drug used with chemotherapy. Forced degradation studies were performed on palonosetron to study its stability behavior. The drug was subjected to acid, base, neutral hydrolysis, oxidation, thermal and photolytic conditions. Mass analysis has been performed to elucidate the oxidative degradants by Advion compact mass spectrometer. HPLC separation was achieved on PerfectChrom 100 C4 (250 × 4.6 mm, 5 μm particle size) column using buffer (20 mM dipotassium hydrogen orthophosphate, adjusted with phosphoric acid to pH 2.5):acetonitrile:methanol (60:30:10, v/v) as the mobile phase with isocratic mode at a flow rate of 1 mL/min using photodiode array detector (PAD) at 210 nm. The method showed adequate sensitivity concerning linearity, accuracy and precision over the range of 0.1–10 μg/mL. Limit of detection (LOD) and limit of quantification (LOQ) were determined to be 0.03 μg/mL and 0.09 μg/mL, respectively. HPTLC separation was carried out on aluminum plates pre-coated with silica gel 60 F254 using methanol:ammonia (10:0.5, v/v) as the mobile phase. CAMAG scanner was operated at 254 nm for the densitometric measurement in the absorbance mode. A polynomial relationship was constructed in concentration range of 0.1–2 μg/band, with LOD and LOQ 0.02 μg/band and 0.06 μg/band, respectively. The cited chromatographic methods were successfully applied to the determination of palonosetron in the presence of its degradation products and additives in the commercially available vials. Method validation was performed as per the ICH guidelines confirming methods robustness to be used in quality control laboratories. Statistical comparisons have been performed between the results of the cited chromatographic methods and those of the official one using Student’s t test and F test values at 95% confidence interval level, revealing good accuracy and precision.

This work describes a dual-mode colorimetric and fluorometric nanoprobe for determination of ketamine hydrochloride (KET) in soda beverages. KET is a widely known club drug that is spiked in beverages to get rape victims vulnerable. The proposed nanoprobe utilizes gold nanoparticles (AuNPs) and fluorescent carbon dots (CDs). AuNPs act as a color probe and quencher of CDs fluorescence. KET destabilizes the citrate-capped AuNPs leading to a color change and subsequent disruption of the inner filter quenching mechanism in this acceptor/donor pair. Nanoparticles are characterized by transmission electron microscopy as well as molecular absorption and emission spectroscopy. The dual-detection mode has been optimized for the concentration of nanoparticles, reaction time and medium pH. The fluorescence recovery efficiency of CDs and the absorbance ratio of AuNPs bands are used as analytical signals for dual detection of KET. A linear response in the range of 5 × 10−5–6.5 × 10−4 mol L−1 is achieved for the fluorescent sensor, with a detection limit of 2.32 × 10−5 mol L−1. The respective values for the color sensor are 1 × 10−4–9 × 10−4 and 2.70 × 10−5 mol L−1. The selectivity of this dual-mode nanoprobe has been investigated by application to different spiked soda drinks. The sensor exhibits good selectivity towards Sprite® and Coca-Cola® in the average oral KET dose; however, the orange coloration in Fanta® seems to have high absorbance over the AuNPs characteristic band that hinders the detection of KET at the average concentration level.

Stability and impurity profiling are in high demand to guarantee the potency, safety and efficacy of new formulations along with their shelf-life. In this study, stability testing of alfuzosin (ALF) and solifenacin (SOL) in their newly co-formulated capsules was conducted under different stress conditions. The obtained degradation products were structurally elucidated and found to be their official impurities, namely; ALF impurity-D and SOL impurities-A, E & I. A selective and reliable stability-indicating HPLC method was developed for assaying the cited drugs along with three of those official impurities. Chromatographic separation was accomplished within 8 minutes using a XBridge® C18 column as the stationary phase and acetonitrile : phosphate buffer (pH 8) : triethylamine (60 : 40 : 0.02, by volume) as the mobile phase at a flow rate of 1.3 mL min−1. Quantification of the analytes was performed at 210 nm using a diode array detector through which peak purity was assessed. The proposed method was validated as per ICH guidelines and it was successfully applied for the determination of the cited drugs in their combined pharmaceutical formulation with percent recoveries of 100.47 and 100.15 for ALF and SOL, respectively. Moreover, the proposed method was exploited for the assessment of the two drugs' stability in Solitral® capsules under accelerated storage conditions. The method was further extended for studying the degradation kinetics of the two drugs.

Abstract A promising combination of tamsulosin HCl and tadalafil has recently been introduced for treating two prevalent and associated urological disorders: benign prostate hyperplasia and erectile dysfunction. Novel HPTLC methods were designed and validated for assaying the cited drugs in their challenging combined formulation. Separation was achieved using HPTLC silica gel 60?F254 plates as a stationary phase with a densitometric measurement at 280?nm. The proposed methods with two different chromatographic systems were successfully applied: a conventional mixture (method I) of ethyl acetate?toluene?methanol?ammonia (5:3:2:0.5, by volume) and a greener one (method II) with ethyl acetate?ethanol?ammonia (8:2:0.1, by volume). The two methods were evaluated through a comparative study in terms of selectivity, tailing factor, developing time and concentration ranges. The greenness profile for each method was then appraised with several green guides, namely GlaxoSmithKline solvent sustainability guide, Environmental, Health and Safety (EHS) tool, National Environmental Method Index (NEMI) and Eco-scale. Moreover, method specificity and peak homogeneity were evaluated by peak purity assessment using the winCATS? software spectral correlation tool. The methods have potential for being simple, fast, economic and selective, and the greener one could be a good option for sustainable analysis of the drugs.

Paper-based microfluidic device was designed with wax-printing to combine potentiometric, fluorimetric and colorimetric detection zones. This newly developed trimodal paper chip has been used for on-site determination of ketamine hydrochloride (KET) as a date rape drug in beverages. The device employed polyaniline nano-dispersion as conducting polymer in ion sensing paper electrodes designed to fit USB plug connector. Carbon dots-gold nanoparticles and cobalt thiocyanate were used in fluorescence and color detection zones, respectively. Cellular phone’s camera facilitated the on-site fluorimetric and color detection. The implemented trimodal detection system exhibited specificity for KET detection in the presence of several other beverage interferences i.e., biogenic amines. This innovative sensor brings together analytical figures of merit for effective KET detection in single aliquot of spiked beverages. The proposed paper-based chip also fulfils WHO criteria for point-of-care devices posing the proposed trimodal paper device as an active part for rapid, on-site drug diagnostics and to be applied further for other similar drugs.

A novel combination of tamsulosin hydrochloride and tadalafil is recently available for treatment of benign prostatic hyperplasia and erectile dysfunction. For the first time, four simple, accurate, smart and robust spectrophotometric methods have been suggested for their simultaneous quantification. The methods, namely; first derivative, ratio difference, derivative ratio and mean centering of ratio spectra, successfully resolved the spectral overlap of their challenging binary mixture. Calibration curves were linear at 2.0–40.0 and 2.0–55.0 μg/mL for tamsulosin hydrochloride and tadalafil, respectively. The methods were validated according to ICH guidelines and statistically compared with the official ones, revealing no considerable difference with respect to accuracy and precision. Specificity of the developed methods was assessed by evaluating various laboratory prepared mixtures. Furthermore, the methods were successfully applied for the quantification of the two drugs in their combined dosage form.

Stability and impurity profiling of new drug formulations are now receiving great attention in modern pharmaceutical analysis. In this work, a novel stability-indicating HPTLC coupled with densitometric quantification was developed for the simultaneous determination of alfuzosin (ALF) and solifenacin (SOL) along with their degradation products/official impurities. The two drugs were subjected to different stress conditions. ALF was liable to acidic and basic hydrolysis, while SOL was found to be susceptible to basic and oxidative degradation. The obtained degradation products, namely; ALF impurity-D and SOL impurities-A, E and I were then characterized by IR and mass spectrometry. Chromatographic separation was then performed on HPTLC silica plates 60 F254, as a stationary phase, using ethyl acetate: toluene: ethanol: ammonia (5: 2: 3: 0.4, by volume), as a mobile phase. The plates were scanned at 220 nm and visualized by iodine vapor in daylight. Effect of different factors, including the mobile phase composition and the detection wavelengths, were carefully studied to achieve the optimum conditions for chromatographic separation. Calibration curves were constructed over the ranges of 0.8 – 30.0 µg/band for ALF and SOL, 0.5 – 15.0 µg/band for ALF imp-D, 0.5 – 4.0 µg/band for SOL imp-I and 0.75 – 7.50 µg/band for SOL basic degradation. The method was also exploited for assessment of the two drugs’ stability in Solitral® capsules under accelerated storage conditions. The proposed method has many potentials of being simple, economic and selective making it an attractive procedure in analyzing not only the two cited drugs but also their impurities.

Multiplex ion analyzers have been introduced recently for the assay of several inorganic ions, whilst electrochemists have extensively employed screen printed sensors for pharmaceutical analyses. This work aims to develop a USB pluggable sensor with a user-friendly design for multiplex analysis of oppositely charged co-formulated organic ions. The miniaturized screen-printed electrode was developed using silver ink on paper substrate. A compact sensor design was attained by including three electrodes, a single reference electrode along with an indicator electrode for each of the determined ions. Optimized PVC membranes were drop-casted over each of the indicator electrodes for the determination of phenylephrine HCl (PHE) and ibuprofen (IBU). The proposed multiplex potentiometric sensors exhibit Nernstian slopes of 59.2 ± 0.26 and -56.8 ± 0.16 mV/decade for PHE and IBU, respectively, with respective detection limits of 1.6 × 10-7 and 6.53 × 10-8 mol L-1. The fast and stable response of the developed sensor enabled the real-time monitoring of the combined dosage form dissolution. The dissolution profiles obtained by this potentiometric analyzer and an off-line separation technique were compared favourably, albeit our proposed in-line sensor reduced waste and time of analysis. The developed method successfully complies with the most demanding stipulations of green analytical chemistry.