Hala Elsayed Zaazaa

Objectives: Three stability-indicating analytical methods featuring outstanding sensitivity, selectivity, and precision were set up for the quantification of salicylamide (SAD) and ascorbic acid (ASC) in the presence of salicylic acid (SAL), which represents a possible impurity and degradation product of SAD. The aim was to develop sensitive, selective, precise, and eco-friendly assays appropriate for routine quality control of pharmaceuticals. Methods: Method (A) was a spectrophotometric technique of a successive derivative of ratio spectra built upon a two-step derivatization of ratio spectra utilizing double-distilled water as a solvent. SAD was quantified at 247.2 nm and 257.0 nm, and ASC at 251.8 and 259.8 nm, while SAL was quantified at 305.6 nm. Technique (B) relied on ratio spectra for the mean centering analytical process applied via two sequential stages, where the amplitudes derived after the second ratio spectra of the mean centering have been recorded on 291.0, 266.0, and 241.0 nm for SAD, ASC, and SAL, in that order. Method (C) involved TLC densitometric analysis, in which the separation was carried out upon plates of silica gel with chloroform–hexane–methanol–acetone–formic acid (5:3:2:1:0.2, in volumes) as a mobile phase, monitored by densitometric detection at 240 nm. The linear relationships were observed over concentration ranges of (0.2–2 µg/band) for SAD with ASC and (0.1–1 µg/band) for SAL. Validation of the presented techniques was performed in accordance with ICH strategies. Results: These developed techniques have been effectively analyzed for SAD with ASC in pharmaceutical dosage forms with non-interfering ingredients. A statistical comparison with the previously used HPLC technique revealed no considerable difference in terms of accuracy and precision. Greenness assessment using the AGREE platform produced scores of 0.72 for the spectrophotometric approach (benefiting from aqueous solvent) and 0.62 for HPTLC (limited by chloroform). Practical applicability (BAGI = 80 for both spectrophotometry and HPTLC) and overall quality indices (CACI = 83 for spectrophotometry; 80 for HPTLC) supported routine QC suitability. Conclusions: The three developed stability-indicating methods are accurate, precise, and selective for simultaneous assay of SAD and ASC in the presence of SAL and are suitable for quality control use. The spectrophotometric procedures combine high analytical performance with an improved environmental profile, while HPTLC offers comparable analytical reliability with slightly lower greenness due to organic solvent use.

Valnemulin hydrochloride (VML), a critical antibiotic used in swine medicine, poses significant toxicity risks—including hepatotoxicity and microbial resistance—when misdosed in livestock. To address this, a green, disposable polyaniline-based solid-contact ion-selective electrode (SC-ISE) was developed for rapid VML quantification in veterinary pharmaceuticals and farm samples. The sensor integrates calix[8]arene as a high-affinity ionophore, enabling detection at therapeutically relevant levels (1.0 × 10 ⁻⁶ to 1.0 × 10 ⁻² mol l ⁻¹ ) with a Nernstian slope (57.27 ± 0.4 mV decade ⁻¹ ) and ultra-low detection limit (3.31 × 10 ^–7 mol l ⁻¹ ). The proposed sensor demonstrated a rapid response time of 20 ± 3 s and a long operational lifetime of up to one month. Crucially, the electrode selectively distinguishes VML from its degradation products and common interferents (e.g., feed additives, ions). Validation in swine serum and feed samples confirmed accuracy (98%–102% recovery), outperforming HPLC. Green metrics (Eco-Scale: 85, AGREE: 0.82) underscore its sustainability vs lab-based methods. By enabling on-farm toxicity prevention, this sensor offers a proactive solution to safeguard animal welfare and combat antibiotic resistance.

A cost-effective, selective, sensitive, and operational TLC-densitometric approach has been adapted for the concurrent assay of Hydroxyzine Hydrochloride (HYX), Ephedrine Hydrochloride (EPH), and Theophylline (THP) in their pure powder and pharmaceutical forms. In the innovative TLC-densitometric approach, HYX, EPH, and THP were efficaciously separated and quantified on a 60F₂₅₄ silica gel stationary phase with chloroform–ammonium acetate buffer (9.5:0.5, v/v) adjusted to pH 6.5 using ammonia solution as a mobile liquid system and UV detection at 220 nm. The novel TLC method validation has been performed in line with the international conference for harmonization (ICH) standards and has been effectively used for the estimation of the researched medicines in their pharmaceutical formulations without intervention from excipients. Additionally, parameters affecting the chromatographic analysis have been investigated. The new TLC approach’s functionality and greenness were appraised using three modern and automated tools, namely the Blue Applicability Grade Index (BAGI), the Analytical Greenness metric (AGREE), and the Green Analytical Procedure Index (GAPI) tools. In short, the greenness characteristics were not achieved as a result of using mandatory, non-ecofriendly solvents such as ammonia and chloroform. On the contrary, the applicability and usefulness of the novel TLC approach were attained via concurrent estimation for the three drugs using simple and straightforward procedures. Moreover, the novel TLC method outperforms previously published HPLC ones in terms of the short run time per sample and moderate pH value for the liquid system. According to the conclusions of comparisons with previously recorded TLC methods, our novel HPTLC method has the highest AGREE score, so it is the greenest HPTLC strategy. Moreover, its functionality and applicability are very appropriate because of the simultaneous assessment of three drugs in one TLC run. Furthermore, no tedious and complicated extraction and evaporation processes are prerequisites.

Butylated hydroxytoluene (BHT) and butylated hydroxyanisole (BHA) are two antioxidants that have been extensively used in many applications. Both are well known for their debatable health risks due to their multiple intake sources. Therefore, conservative limits are set for them in different regulations adapted to the matrices in which they exist. Here we present a simple spectrofluorimetric method for the determination of BHT and BHA based on their native fluorescence and synchronous scanning mode. The type of solvent and the interval between emission and excitation wavelengths were carefully optimized. Under the optimized conditions, good linearities were obtained between the emission intensity and the corresponding concentrations of BHT and BHA over the range of 3–18 µg/mL and 0.1–7 µg/mL, respectively with a good correlation coefficient (r > 0.99). The limits of detection were 0.9 and 0.02 µg/mL, and the quantification limits were 3 and 0.05 µg/mL for BHT and BHA, respectively. The suggested procedure was validated according to ICH guidelines Q2 (R1). Furthermore, the method’s greenness was assessed by three different methods, and it proved to be eco-reasonable. The method was successfully applied to the determination of BHT and BHA in pharmaceutical formulations. We also applied the suggested method for monitoring the residual BHA in conventional, powdered milk and butter, with good recovery in spiked samples.

High performance liquid chromatography is one of the techniques of choice for the separation and quantitative determination of drugs in mixture form. Ipriflavone, ascorbic acid, pyridoxine, vitamin D3, and lysine are formulated together as an adjuvant combination in osteoporosis. In this work, we developed and validated two complementary high performance liquid chromatographic methods to determine the five compounds in their pharmaceutical dosage form. The first method (method A) was capable of determining ipriflavone, ascorbic acid, pyridoxine, and vitamin D3 in their bulk and combined pharmaceutical formulation. The method is based on Liquid Chromatographic separation with UV detection at 254 nm using Agilent Eclipse XDB-C18 column with a mobile phase consisting of 25 mM ammonium acetate buffer (pH 4.2): methanol in gradient mode. Due to the high polarity of lysine, it was difficult to achieve satisfactory retention on reversed phase columns. So, we separated it on a strong cation exchange column (Exsil 100 SCX) without derivatization with a mobile phase consisting of 10 mM sodium dihydrogen phosphate and 200 mM sodium chloride (pH 6) with UV detection at 210 nm (method B). Validation of the proposed methods was performed according to ICH guidelines Q2(R1). The proposed methods proved to be valid for selective analysis of the stated drugs in their bulk and combined pharmaceutical formulation. Greenness assessment of the developed methods was evaluated using three assessment tools: ESA, GAPI and the most recently developed tool AGREE, showing a satisfactory comprehensive guide of the greenness of the developed methods.

Three smart carbon paste electrodes were fabricated to quantify dorzolamide hydrochloride DRZ, including conventional carbon paste I, modified carbon paste embedding Silica II, and modified carbon paste embedding β-cyclodextrin III. This study is based on the insertion of DRZ with phosphomolybdic acid to create an electroactive moiety dorzolamide-phosphomolybdate ion exchanger using a solvent mediator dibutyl phthalate. The three constructed carbon paste electrodes displayed Nernstian responses and linear concentration ranges with lower detection limits. The vital performance of the created electrodes was verified in relation to various parameters. The electrodes enhance the selective determination of DRZ in the presence of inorganic ions, a co-formulated drug in the dosage form timolol maleate, and the excipient benzalkonium chloride. The modified carbon paste electrode including Silica was utilized to detect DRZ in ophthalmic eye drop form utilizing the direct calibration curve and potentiometric titration methods. Satisfactory findings were achieved by comparing them to other reported methods.

Two novel separation methods have been presented for the concurrent assessment of flumethasone pivalate (FP) and clioquinol (CL) in their combinations in ear drop formulations or in the presence of phenoxyethanol preservative (PEP) in their cream formulations. The first method is an innovative thin-layer chromatographic (TLC) method. The optimal separation was accomplished via silica gel aluminum plates F254, with a mixture of benzene, ethyl acetate and formic acid (5:5:0.2, in volumes) as the mobile system. In Method II, a new ultra-high-performance liquid chromatographic method (UHPLC) with a photodiode array detector (PDA) was presented. A reversed-phase inertsil ODS 5 µm C 18 packed column (100 Å, 4.6 mm internal diameter (I.D.) × 50 mm) at 30 °C was employed. Elution was completed in 3 min. Unfortunately, greener solvents were tested as a mobile phase, but an asymmetric peak for CL was noted. In addition, the new UHPLC method has a priority over the old HPLC one by Sayed et al., 2014, in terms of quickness and avoiding interference from the PEP preservative. Concerning the TLC method, the novel TLC method has the advantage of preventing the interference of PEP. This paper represents the first analytical approach for the concurrent assay of FP and CL in the presence of the preservative phenoxyethanol in the cream formulation.

Two rapid, smart and validated stability indicating HPLC and TLC techniques were developed to determine atenolol (ATE) and lercanidipine HCl (LER) simultaneously in their pharmaceutical formulation. HPLC chromatographic separation was implemented by using Microsorb C18 (250 × 4.6 mm, 5 μm) column, with mobile phase of acetonitrile and 20 mM potassium dihydrogen phosphate buffer pH 3.5 adjusted by orthophosphoric acid in the ratio of (65:35, v/v) at a flow rate of 1.2 mL/min at 240 nm also the injection volume adjusted to be 30 μL. These selected conditions effectively separated ATE and LER at a retention time of 2 and 6.7 min, respectively, by isocratic elution mode without any interference from the obtained degradation products of LER. The densitometric determination was performed by using precoated silica gel 60F254 aluminum plates and chloroform, methanol and triethylamine (11.3:1.3: 0.3, by volume) as a developing system. The detection wavelength for simultaneous estimation of both drugs was 240 nm in the presence of the oxidative product of LER. The R_F values for ATE and LER were 0.22 and 0.78, respectively. The calibration curves of both techniques were constructed with linearity ranges of (5–55) μg.mL⁻¹ and (1–55) μg.mL⁻¹ for both ATE and LER, respectively, for HPLC determination. While for TLC, the linearity ranges were (1–4) μg/band and (0.2–1.4) μg/band for ATE and LER, respectively. LER degradation products were characterized using UPLC/MS and the suggested mechanisms and degradation pathways were introduced.