Commercial Pharmaceutical Formulations Research Articles

Monolithic stationary phases prepared via cyclic anhydride ring-opening polymerization as tunable platforms for chromatographic applications.

Polymer monolithic stationary phases were prepared based on a cyclic anhydride as a reactive and tunable platform via ring-opening post-polymerization using primary amines, octadecylamine and benzylamine. The characterization techniques indicated the insertion of the functional groups into the original monoliths and confirmed the amidation reactions. The post-polymerization modification also improved the monolith's thermal and mechanical stability and induced significant improvement in their surface area. The stationary phases were synthesized inside small dimension stainless-steel columns (2.1 mm i.d. × 50 mm length). The prepared columns before and after modifications have been tested for the separation of the alkylbenzene series and some polycyclic aromatic hydrocarbons (PAHs) as model compounds. In all cases, the chromatographic performance in terms of the height equivalent to a theoretical plate on the functionalized monoliths was remarkably improved when compared with that on the unmodified monolith, which was between 9.59-39.49 μm and 4.08-31.50 μm using monoliths modified with octadecylamine and benzylamine, respectively. Under the same chromatographic conditions, the functionalization of monoliths with octadecylamine provided more hydrophobic interactions and enhanced the retention of alkylbenzenes, while the modification of monoliths with benzyl groups improved the separation and the retention of the PAHs through the strong π-π interactions. However, post-modification polymerization with octadecylamine and benzylamine enhanced the separation efficiency of the prepared columns toward all studied compounds. The repeatability of the injections on the same column and the reproducibility of the prepared columns have been studied for some selected parameters and estimated in terms of percent relative standard deviation (%RSD) for some of the studied compounds. The repeatability of the prepared columns was ≤9.42% (n = 5) based on run-to-run injections and ≤9.48% based on day-to-day injections for five successive days. The reproducibility levels, on the other hand, were ≤20.95% for all studied parameters in all cases. To assess their performance for the analysis of real samples, the applicability of the prepared columns was examined for the separation of the active ingredients extracted from some commercial pharmaceutical formulations and for the separation of tea water extract constituents. The validation data show the suitability of the columns for practical use in the routine analysis of these samples.

Efficient and eco-friendly detection of gabapentin using nitrogen-doped carbon quantum dots: an analytical and green chemistry approach.

This study presents the development of an eco-friendly and highly selective mitrogen-doped carbon quantum dot based sensor (N-CQDs) for the detection of gabapentin - a commonly misused drug. A detailed characterization of N-CQDs spectral features and their interaction with gabapentin is provided. The optimal conditions for sensing, including pH value, buffer volume, N-CQDs concentration, and incubation time, were established. The results showed excellent fluorescence quenching at 475 nm (λex = 380 nm) due to the dynamic quenching mechanism, and the sensor demonstrated excellent linearity in the 0.5-8.0 μg mL-1 concentration range with correlation coefficients of more than 0.999, a limit of detection (LOD) of 0.160 and limit of quantification (LOQ) of 0.480 μg mL-1. The accuracy of the proposed sensor was acceptable with a mean accuracy of 99.91 for gabapentin detection. In addition, precision values were within the acceptable range, with RSD% below 2% indicating good repeatability and reproducibility of the sensor. Selectivity was validated using common excipients and pooled plasma samples. The proposed sensor accurately estimated gabapentin concentration in commercial pharmaceutical formulations and spiked plasma samples, exhibiting excellent comparability with previously published methods. The 'greenness' of the sensing system was evaluated using the Analytical GREEnness calculator, revealing low environmental impact and strong alignment with green chemistry principles with a greenness score of 0.76. Thus, the developed N-CQDs-based sensor offers a promising, eco-friendly, and effective tool for gabapentin detection in various situations, ranging from clinical therapeutics to forensic science.

Fabrication of silicon quantum dots-methyl viologen nanohybrids: Turn-On-Off-On fluorescence nanoprobe for the detection of d-penicillamine

This study provides a straightforward, one-step hydrothermal approach for synthesizing water-soluble silicon quantum dots (SiQDs). The surface of the synthesized SiQDs is modified by the carboxylic acid functional group (A:SiQDs) after succinic anhydride treatment. The modified A:SiQDs, which emitted blue light fluorescence, showed high stability against photobleaching, thermal stability, and good water solubility. The A:SiQDs are conjugated with methyl viologen (MV2+) to develop a nanohybrid for specific D-Penicillamine (D-PA) detection with an LOD of 8 nM. The suggested sensor was effectively used to analyze D-PA in commercial pharmaceutical formulations using the conventional addition method, and it produced results with good accuracy and precision that were nearly equal to those measured.

Development of Visible Spectrophotometric Methods for the Determination of Tricyclic Antidepressants Based on Formation of Molecular Complexes with p-Benzoquinones

Tricyclic antidepressants are commonly employed in the management of major depressive disorders. The present work describes two visible (VIS) spectrophotometric techniques that utilize the formation of charge transfer complexes between four antidepressant compounds, namely, amitriptyline hydrochloride (AMI), imipramine hydrochloride (IMI), clomipramine hydrochloride (CLO), and trimipramine maleate (TRI) acting as electron donors and two p-benzoquinones, namely, p-chloranilic acid (pCA) and 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ), serving as electron acceptors. The stoichiometry of the compounds produced exhibited a consistent 1:1 ratio in all instances, as established by Job’s method. Molar absorptivities, equilibrium association constants, and several other spectroscopic properties were determined for all complexes. The developed spectrophotometric techniques were validated intra-laboratory and successfully applied for quantitative assessment of the four antidepressant active ingredients in several commercial pharmaceutical formulations. The methods are relatively simple, fast, and use readily available laboratory instrumentation, making them easily applicable by most quality control laboratories worldwide.

Comparative study of drug release from electrospun nanofibers loaded with clotrimazole via two different approaches using a fully automated sequential injection system

The development of new drug delivery platforms including the use of nanotechnology has been found of great interest in recent years. Two different loading approaches of the model antimycotic drug clotrimazole into the nanofibrous polycaprolactone and polydioxanone structures including electrospinning of a drug-polymer blend and impregnation of nanofibers with drug have been tested. The final amount of clotrimazole in the nanofibrous materials was determined by HPLC analysis and Raman spectroscopy. The electrospinning of blend approach allowed the adsorption of clotrimazole in a quantity of up to 30 % using mixtures with polymer/clotrimazole ratios from 2:1 to 8:1 (w/w). Ethanolic clotrimazole solutions with concentrations from 2.5 to 3.5 mg L−1 were used for adsorbing clotrimazole in blank nanofibers for 1–3 h with final clotrimazole content ranging from 3.0 to 5.7 %. Furthermore, a comparative liberation study including comparison with commercially available creams was carried out in low pressure flow system. The results obtained confirmed well controlled release of clotrimazole from both types of nanofibers. Compared to commercial pharmaceutical formulations containing 1 % clotrimazole where first-order release kinetics was observed, nanofibrous materials provided linear controlled release (zero-order kinetics) in the tested 3 h period.

White targeted chromatographic screening method of Molnupiravir and its metabolite with degradation kinetics characterization and in-silico toxicity

SARS-CoV-2 virus triggered a worldwide crisis, with world nations putting up massive efforts to halt its spread. Molnupiravir (MLN) was the first oral, direct-acting antiviral drug approved for nasopharyngeal SARS-CoV-2 infection with favorable safety and tolerability profile. This study aims at determination of MLN and N4-hydroxycytidine (NHC), its main degradation product and its main metabolite, using sensitive, simple, and green HPLC–DAD method. Moreover, under different stress conditions using NaOH, HCl, neutral, H2O2, dry heat and sun light, the method was applied for MLN assay along with kinetics degradation investigation. The linearity range for MLN and NHC were both 0.1–100 µg/mL with LOD and LOQ of 0.013 & 0.043 and 0.003 & 0.011 µg/mL, for MLN and NHC, respectively. MLN was found to be extremely vulnerable to alkali hydrolysis compared with acid and dry heat degradation. In contrast, MLN was stable under conditions of oxidative, neutral, and sunlight-induced deterioration. Acid and alkali-induced degradation followed pseudo first-order kinetics model. In addition, LC–MS-UV was used to suggest the mechanism of the stress-induced degradation route and to characterize the eluted degradation products. Toxicities of both MLN and its degradation products were evaluated using ProTox-II and they were found to be negligibly harmful. The proposed HPLC–DAD was effectively used for the analysis of MLN in commercial pharmaceutical formulations. The proposed method for MLN determination after greenness and whiteness appraisal was found to be superior compared to the reported methods for MLN analysis.

A Spectrophotometric Approach for Estimating Nimodipine by Oxidative-Coupling Reaction with 4-Aminoantipyrine in its Tablet and Biological Fluids

This study involves the development of a speedy, artless, selective and precise spectrophotometric methodology for the determination of nimodipine in the aqueous medium. The proposed approach was dependent on the oxidation and coupling reaction of nimodipine with 4-aminoantipyrine using KIO3 as an oxidizing agent. A yellow-brown product was fashioned at room temperature which gave a band with maximum absorption at 464 nm. Calibration plot was linear and adheres to Beer's law within the concentration range 1.0- 35 μg/ml with an excellent coefficient of determination (R2=0.9992). The values of molar absorptivity and Sandell's sensitivity were planned and established to be in the consequence of 1.2679x104 l/mol.cm. and 0.033 μg/cm2, correspondingly. The mole ratio of the achieved product has been measured between nimodipine and 4-aminoantipyrine was evaluated to be 1:1. The detection limit (LOD) and quantitation limit (LOQ) were expected and found to be 0.01774 and 0.05914 μg/ml, correspondingly. The recoveries percentage were obtained in the range 97.38%-103.61% while, the precision (RSD) was in the range 0.96%-3.18% depending on the concentration level. The recommended approach was applied successfully to estimate nimodipine in its tablet and in the biological fluids, no intrusions were noticed from the shared excipients additives present in the commercial pharmaceutical formulation.

Determination of vitamin D3 in pharmaceutical products using salting-out assisted liquid–liquid extraction coupled with reversed phase liquid chromatography

A new method, based on salting-out assisted liquid–liquid extraction (SALLE) coupled with HPLC-UV, has been introduced for the analysis of vitamin D3, cholecalciferol, in different pharmaceutical dosage forms. The developed method has been optimized in terms of chromatographic and extraction parameters. Higher yields were obtained when the SALLE was carried out using 10 mL of acetonitrile and 7.5 g of sodium chloride. The proposed method was validated in terms of selectivity, linearity, accuracy, limit of detection (LOD), limit of quantification (LOQ), robustness, and stability of vitamin D3 in solution. The method was linear with r2 > 0.999 over the range of 100–300 IU.mL−1. Recovery was within 98.80–100.43 % of the nominal vitamin D3 and the relative standard deviation values of the precision study were less than 2.0%. The LOD and LOQ were 3.17 IU.mL−1 and 9.61 IU.mL−1, respectively. Vitamin D3 in different commercial pharmaceutical formulations was analyzed using the developed method and the results were compared to those obtained using the pharmacopeial USP method. Low deviations (0.2–5.9%) between the two methods were obtained, suggesting that the developed method could replace the well-known USP method. The SALLE method proposed in this study offers a simpler and more efficient approach, requires smaller volumes of less toxic organic solvents and significantly reduces the analysis time needed to determine vitamin D3. Consequently, the SALLE method can be a promising alternative to the conventional pharmacopeial method used for vitamin D3 determination in dosage forms as it resolves most of the drawbacks associated with the pharmacopeial method.

Graphite-polyurethane composite electrode modified with nickel(II) nanoparticles submitted to electrochemical pretreatment in basic medium for the determination of atenolol

A new approach for the determination of atenolol (ATN) at a graphite polyurethane composite electrode (GPUE) modified with electrodeposited nickel(II) nanoparticles electrochemically pretreated in alkaline medium (GPUE-NiNP) is reported. The electrodeposition of NiNP on the GPUE surface was performed by 5 scans in cyclic voltammetry between 0.0 to −1.5 V (vs. SCE) and scan rate of 20 mV s−1 in a 0.05 mol L−1 NiSO4 and 0.32 mol L−1 H3BO3 solution at pH 5. After deposition, the GPUE-NiNP was submitted to an electrochemical pretreatment in 0.50 mol L−1 NaOH by cyclic voltammetry at 100 mV s−1. The best results were obtained after 50 cycles at 100 mV s−1. Quantitative measurements at GPUE-NiNP were performed using differential pulse voltammetry (DPV) in pH 11 universal buffer. Atenolol promotes a decrease in the nickel oxide signals probably due to a complexation of the analyte with free Ni2+ in solution. Thus, the analyte was quantified by the signal suppression and an analytical curve was obtained at the GPUE-NiNP using the optimized conditions for 1.0 to 100 x 10−8 mol L−1 atenolol between 1.0 and 0.0 V (vs. SCE) with a linear range between 2.0 x 10−8 and 1.0 x 10−7 mol L−1 and a limit of detection of 3.47 x 10−9 mol L−1 with R = 0.9995 for GPUE-NiNP. The procedure was applied to three commercial pharmaceutical formulations with recoveries between 99.5 and 100.7% and agreed with a comparative HPLC procedure within 95% confidence level according to the Student’s t-test.

Development and validation of a new spectrophotometric method for simultaneous determination of sitagliptin and metformin hydrochloride in tablet pharmaceutical dosage forms using chemometrics technique in comparison with HPLC

A new, quick, easy, affordable and eco-friendly simultaneous spectrophotometric method for determining a combined sitagliptin and metformin hydrochloride in pharmaceutical formulations was developed and validated using two chemometrics technique. These two methods are the partial least square (PLS) and principal component regression (PCR). They do not need to do a sample preparation or separation before analysis. Various drug concentrations and instrumental spectra of 25 mixed solutions of a combination of sitagliptin and metformin hydrochloride were used for model construction in the range of 200�270 nm. The R2 values of 0.9994 and 0.9996 assigned for the PLS of the sitagliptin and metformin hydrochloride and that of 0.9987 and 0.9996 for the PCR of the sitagliptin and metformin hydrochloride, respectively. It is noteworthy that these two models were successfully and effectively used with the commercial pharmaceutical formulations. Finally, the statistical comparison revealed no significant differences with the results of the HPLC reference method. The proposed method is dependable to be adopted as an alternative analytical method in the pharmaceutical industry�s quality control.

A Mid-Infrared Spectrophotometric Method for Simultaneous Quantification of Naltrexone and Bupropion with Multivariate Calibration

Naltrexone (NTX) and bupropion (BUP) are used in combination in clinical practice for obesity; however, the existing analytical methods for this drug combination are not sustainable. This work aims to develop an analytical method that is faster, easier and less expensive compared with high performance liquid chromatography (HPLC) and involves green technology without solvents to quantify BUP and NTX in combination. The objective was to validate a method using mid-infrared (MIR) spectroscopy associated with multivariate calibration and chemometrics to simultaneously measure NTX and BUP in a pharmaceutical capsule form. The models were developed using MIR spectroscopy with diffuse reflectance, with interval partial least squares (iPLS) variable selection. The working range selected to optimize the model was from 1885.8 to 1585.4 cm-1. The chosen model was obtained with partial least squares (PLS2) and with data pre-processed by first derivative Savitzky-Golay smoothing followed by mean centering, using four latent variables, providing a root mean square error of prediction of 1.8 mg g-1 for NTX and 6.42 mg g-1 for BUP. The method was validated according to current international standards. In conclusion, the methods developed in the MIR region provided statistically similar results to the validated chromatographic method for commercial pharmaceutical formulations.

Voltammetric approach for pharmaceutical samples analysis; simultaneous quantitative determination of resorcinol and hydroquinone

A simple and precise analytical approach developed for single and simultaneous determination of resorcinol (RC) and hydroquinone (HQ) in pharmaceutical samples using carbon paste electrode (CPE) modified with 1-Ethyl-3-methylimidazolium tetrafluoroborate as ionic liquid and ZnFe2O4 nanoparticle. A significant enhancement in the peak current and sensitivity of the proposed sensor observed by using modifiers in the composition of working electrode compared to bare CPE which is in accordance with the results obtained from electrochemical impedance spectroscopy investigations. Electrochemical investigations revealed a well-defined irreversible oxidation peak for RC over a wide concentration range from 3.0 µM to 500 µM in 0.1 M phosphate buffer solution (pH 6.0) with the linear regression equations of Ip (µA) = 0.0276 CRC (µM) + 0.5508 (R2 = 0.997). The limit of detection and quantification for RC analysis were found to be 1.46 µM and 4.88 µM, respectively. However, the obtained SW voltammograms for simultaneous determination of RC and HQ exhibited a desirable peak separation of about 360 mV potential difference and a satisfactory linear response over the range of 50–700 µM and 5-350 µM with the favorable correlation coefficient of 0.991 and 0.995, respectively. The diffusion coefficient (D) of RC and the electron transfer coefficient (α) at the surface of ZnFe2O4/NPs/IL/CPE estimated to be 2.83 × 10− 4 cm s− 1 and 0.76. The proposed sensor as a promising and low-cost method successfully applied for determination of RC in commercial pharmaceutical formulations such as the resorcinol cream of 2% O/W emulsion available on the market with the recovery of 98.47 ± 0.04.

Electrochemical oxidation of meglumine in a pharmaceutical formulation using a nanocomposite anode

The electrocatalytic oxidation of meglumine and gadoterate meglumine (Gd-DOTA) on a TiO2-Ni(SO4)0.3(OH)1.4 composite anode was investigated in alkaline medium (5 M KOH) using cyclic voltammetry and chronoamperometry. The composite was prepared by hydrothermal method and the morphology and structure of the produced nanoparticles were studied by scanning electron microscopy with energy-dispersive X-ray spectroscopy, X-ray diffraction, atomic force microscopy, BET surface area analysis and Fourier transform infrared spectroscopy. The characterization revealed the formation of Ni(SO4)0.3(OH)1.4 nanobelts dispersed on TiO2 nanoaggregates. The composite was coated onto a porous graphite rod, showing good adherence without requiring any binder (according to their anodic and cathodic charges). The supported composite was electrocatalytic, allowing the oxidation of meglumine, either as pure reagent or contained in gadoterate meglumine solutions. Electrochemical methods allowed determining the kinetic parameters, such as the electron transfer coefficient α, the total number of electrons n and the standard heterogeneous rate constant k0 for the reaction of meglumine. The chronoamperometric tests informed about the good stability of the composite anode upon meglumine oxidation at +0.6 V for 10 h. The electrochemical oxidation of meglumine in a commercial pharmaceutical formulation (Dotarem®) was corroborated via ultra-high performance liquid chromatography coupled to electrospray ionization and quadrupole time-of-flight mass spectrometry.

A Validated HPLC Multichannel DAD Method for the Simultaneous Determination of Amoxicillin and Doxycycline in Pharmaceutical Formulations and Wastewater Samples

The quality of marketed pharmaceutical formulations must be guaranteed to attain better remedial effects and lower toxicity. The wide exploitation of antibiotics may lead to their presence as residues in body fluids and wastewaters, potentially toxic to human health. Consequently, determining antibiotics in pharmaceutical formulations and water samples is of significant importance. This paper aims to explore the possibilities of a high-performance liquid chromatography coupled with diode array detection (HPLC-DAD) method to obtain a simple, fast, and efficient analytical tool for the simultaneous determination of antibiotics in pharmaceutical formulations and environmental samples. The method was completely validated with regard to specificity, linearity, detection and quantification limits, precision, accuracy, and robustness according to the requirements of existing guidelines, and was proven to be reliable and suitable for the envisioned application. The linearity study was conducted for the calibration curves in the range of 10–100 μg/mL. The limits of detection and quantification were found to be 0.2 and 0.7 μg/mL for amoxicillin and 0.3 and 1.0 μg/mL for doxycycline, respectively. The high recovery of drugs from their commercial pharmaceutical formulations (93%) and from wastewater samples (98%) indicated good accuracy and precision. The method is robust for small or deliberate changes to the chromatographic parameters, and it was successfully applied for the quantitative determination of amoxicillin and doxycycline in wastewater and commercial tablets. The obtained results proved that the validated method is appropriate for its intended use in the routine quality control and assay of both antibiotics studied.

Application of net analyte signal and principal component regression for rapid simultaneous determination of Levodopa and carbidopa in commercial pharmaceutical formulation and breast (human) milk sample using spectrophotometric method

In this study, a UV–vis spectrophotometric method coupled with net analyte signal (NAS) and principal component regression (PCR) as multivariate calibration methods were used for the simultaneous determination of levodopa (LEV) and carbidopa (CBD) in prepared mixtures, pharmaceutical formulation, and breast milk sample. The mean recovery of the NAS model was 98.10% and 99.60% for LEV and CBD, respectively. Also, the relative standard deviation (RSD%) values were found to be lower than 5.5% and 4% for LEV and CBD, respectively. On the other hand, the mean recovery of LEV and CBD related to the PCR method was obtained at 96.86% and 92.43%, respectively. K-Fold cross-validation was used to estimate the number of components, which was 7 and 3 with a mean square error prediction (MSEP) of 1.50 and 7.14 for LEV and CBD, respectively. The results revealed that the NAS model was better than the PCR model. Additionally, the proposed NAS-based calibration method was successfully developed for the simultaneous analyses of LEV and CBD in a commercial tablet and breast milk.

Two New HPLC Methods, Assessed by GAPI, for Simultaneous Determination of Four Antipsychotics in Pharmaceutical Formulations: A Comparative Study

Antipsychotics are widely used to treat various mental disorders. Combination therapies were approved by the FDA to treat manic states. Quetiapine fumarate, aripiprazole, asenapine maleate, and chlorpromazine HCl are frequently used for treatment of these disorders. Green analytical chemistry is primarily concerned with reducing waste generated during sample preparation or analysis. Green solvents, such as ethanol, are being used in HPLC as an alternative to acetonitrile. To this purpose, two new chromatographic methods were developed to determine these four drugs simultaneously in their bulk and pharmaceutical formulations. The greenness of both methods was assessed by the green analytical procedure index (GAPI)—one of them was found to be green ecofriendly, and the other had some environmental hazards (conventional)—and this helps laboratories to choose a method that suits their capabilities. The chromatographic separation for both methods was carried out on a Thermo® C18 column. The total separation times were about 11 min and 9 min for the green and the conventional methods, respectively. Using the Student’s t-test and the F-ratio, there was no significant difference between the results of the two methods. These methods have been validated and successfully applied to the analysis of commercial pharmaceutical formulations. Our study could successfully be used in central quality control laboratories, which need a single analytical method to separate more than one compound with similar pharmacological action.

Protein nano Dots conjugated AuNP, poly-Lysine biointerface for the selective voltammetric estimation of Melatonin in pharmaceutical and food samples

Attributed to the compromised charge transfer of Protein-derived nanomaterials, their beneficial traits as an extraordinarily selective and specific biorecognition element for the electrochemical sensors haven’t been fully exploited. Here in this work, we report a facile approach to electrochemically fabricate a Protein Nanodots (PNDs) conjugated AuNP, poly-Lysine biointerface for the voltammetric estimation of Melatonin. Using bovine serum albumin, PNDs decorated with active functional groups were derived and further tailored with AuNP-poly Lysine to achieve the facilitated charge-transfer and specific interactions with Melatonin. After detailed topographical and chemical characterization of the fabricated surface, its ability to estimate Melatonin was probed in a linear concentration range of 0.1–200 µM. The fabricated biointerface manifested a ∼3-fold magnification in Mel peak current with a potential shift of ∼60 mV compared to the unmodified electrode. The potential shift was attributed to the synergistic effect of PNDs and Au-poly-Lysine layer leading to the electro-catalytic behavior and facilitated charge-transfer due to specific interactions between Melatonin/AuNP-PLL/PND. Consequently, sensor demonstrated a LOD of 31.6 nM without any substantial interference of Uric acid, Ascorbic acid, and Hypoxanthine. The estimation of Melatonin in commercial pharmaceutical formulation as well as food sample (Mung Beans) was carried out to investigate the practical application.

Ecofriendly Spectrophotometric Methods for the Simultaneous Determination of Flupirtine Maleate and Thiocolchicoside: Evaluation of Greenness Profile

The present study represents four simple UV spectrophotometric methods that are accurate, precise, and ecofriendly for estimating flupirtine maleate and thiocolchicoside in pharmaceutical formulation. The four methods are the second order derivative of zero order spectra, the first derivative of ratio spectra, the extended ratio subtraction technique, and the absorption factor method. The proposed methods have linear calibration curves in the range of 14-26 to 2.80-5.2 µg mL-1 for flupirtine maleate and thiocolchicoside, correspondingly. The proposed methods are evaluated toward synthetic mixtures of the drugs as mentioned earlier and then extended to commercial pharmaceutical formulations of the analytes of interest. The findings of the assay for determining the cited drugs in pharmaceutical tablets were statistically analysed with those of the published HPLC method, implying that no discernible difference exists between the suggested and published procedures. The analytical Eco scale, Agree metrics, and Green analytical procedure index was used to assess the method's greenness scores. The methods have been validated according to ICH criteria and confirmed to be within acceptable limits.

Impurity-profiling UPLC methods for quantitative analysis of some antiemetics formulated with pyridoxine.

Cyclizine hydrochloride (CYC) and meclozine hydrochloride (MEC) are antihistaminic drugs generally co-formulated with pyridoxine hydrochloride (PYR) to treat nausea and vomiting in pregnancy. Several analytical techniques have been applied for the determination of CYC or MEC with PYR, but determination of CYC impurity; benzhydrol (BEH) or MEC impurity; or 4-chlorobenzophenone (BEP) has not been paid attention to. Therefore, micellar UPLC method is introduced for analysis of ternary mixtures containing PYR together with both CYC and BEH (mixture I) or MEC and BEP (mixture II). Chromatographic separation was achieved using a Hypersil gold C8 column (50 × 2.1mm, 1.9μm) using 0.01 M sodium dodecyl sulfate modified to pH3.5 using phosphoric acid:acetonitrile (45:55 by volume) for mixture I and 0.1% sodium dodecyl sulfate, 0.1% sodium bicarbonate adjusted to pH2.6 by phosphoric acid:acetonitrile (47:53 by volume) for mixture II as mobile phases. The separated peaks were detected at 230 and 245 nm for mixtures I and II, respectively. The adopted methods were validated in conformance with the International Conference on Harmonization (ICH) recommendations and were properly applied in commercial pharmaceutical formulation analysis. Comprehensive ecological comparison was achieved, confirming a higher ecological value of the presented methods compared to the earlier reported methods.

Graphite-Polyurethane Composite Electrode Modified with Molecularly Imprinted Polymer for Determination of Diclofenac

A molecularly imprinted polymer (MIP) was prepared using the anti-inflammatory diclofenac (DCF) as a template. A non-imprinted polymer (NIP) was also prepared as a control. These MIP and NIP were characterized by scanning electron microscopy (SEM), transmission electron microscopy (TEM) and Brunauer-Emmett-Teller (BET), revealing a higher porosity in the first. Then both were used in the modification of graphite-polyurethane composites electrodes (GPUE). Differential pulse anodic stripping voltammetry was used for DCF determination at GPUE-MIP-DCF containing 2.5% (m/m) of the modifier in perchloric acid, pH = 2.0, after previously optimized conditions such as 300 s of accumulation time, +0.2 V accumulation potential (vs. SCE (saturated calomel electrode)), 50 mV pulse amplitude and 10 mV s–1 scan rate. A linear dynamic range from 0.010 to 0.20 μmol L–1 and a limit of detection (LOD) of 0.99 nmol L–1 were found, using GPUE-2.5-MIP-DCF. DCF was determined in commercial pharmaceutical formulations and in synthetic urine samples, with recoveries between 101 and 102% (n = 3) and 101% (n = 3), respectively. The results agreed with the reference high-performance liquid chromatography (HPLC) within 95% confidence level, according to Student’s t-test. Interference from meclofenamic and mefenamic acids, which are structurally similar to DCF, was also evaluated. Interferences could not be totally avoided, but MIPs presented a considerable ability in discriminating the voltammetric response for DFC, despite the close structural similarity with the interferents.