Quality Control Laboratories Research Articles

Comparative study of continuous wavelet transform and multivariate calibration for the simultaneous spectrophotometric determination of tamsulosin and solifenacin in combined dosage form and biological sample.

Spectrophotometry alone is not applicable for the simultaneous determination of drugs in a multi-component pharmaceutical formulation owing to their overlap. In this study, the combination of UV-Vis spectrophotometry and chemometric methods, including continuous wavelet transform (CWT) and partial least squares (PLS) was presented for the simultaneous estimation of tamsulosin (TAM) and solifenacin (SOL) in synthetic mixtures, commercial formulation, and biological sample. The simultaneous spectrophotometric determination of TAM and SOL in binary mixtures, real sample, and biological sample was performed by applying CWT and PLS approaches. In the CWT method, two various wavelet families named Daubechies (db2) at wavelength 223 nm and Biorthogonal (bior1.3) at wavelength 227 nm based on the appropriate zero crossing point were selected for TAM and SOL, respectively. The linear ranges of TAM and SOL were 0.25-4 μg/mL and 10-30 μg/mL, respectively. The limits of detection (LOD) were 0.0459 μg/mL and 0.2085 μg/mL, while the limits of quantitation (LOQ) were 0.3208 μg/mL and 0.6495 μg/mL for TAM and SOL, respectively. The average recovery values of eighteen mixtures were 98.28% and 97.79% for TAM and SOL, respectively. Also, the root mean square error (RMSE) of both components was lower than 2.3. Based on the k-Fold cross-validation in the PLS approach, the optimum number of components related to the TAM and SOL were 9 and 5 with a mean square error prediction (MSEP) of 0.0153 and 0.0370, respectively. The mean recovery values of the test set were found to be 100.09% for TAM and 99.95% for SOL where RMSE values were 0.0064 and 0.0169 for TAM and SOL, respectively. Analysis of variance (ANOVA) was applied to the results of the real sample that there was no significant difference between the proposed methods and the high-performance liquid chromatography (HPLC) as a reference technique. The result obtained revealed that the proposed methods were found to be fast, facile, economical, and precise, which provide a suitable alternative to HPLC technique for the concurrent determination of TAM and SOL in quality control laboratories. UV-Vis spectrophotometry combined with CWT and PLS was developed.Simultaneous analysis of TAM and SOL was performed using the proposed approaches.These methods were implemented on synthetic mixtures, commercial formulation, and biological sample.ANOVA test was used to compare the suggested methods and the HPLC technique.

An eco-friendly HPLC method for concurrent determination of carbocisteine, guaifenesin, and oxomemazine in their combined formulations

The respiratory tract infections have a growing concern by healthcare specialists. Carbocisteine, guaifenesin, and oxomemazine are widely used as co-formulated anti-cough drugs. For the first time, a precise, accurate, and green HPLC method has been developed and validated for their determination in their combined dosage forms. The separation was accomplished using a photodiode array detector at 220 nm with an isocratic green mobile phase consisting of phosphate buffer 0.025 M, (pH 3) and ethanol (75:25, v/v) at a flow rate of 1.0 mL/min and ambient temperature. The developed method was validated in accordance with ICH guidelines. Carbocisteine, guaifenesin, and oxomemazine were separated in less than 12 min at 1.569 ± 0.005 min, 8.546 ± 0.007 min, and 10.877 ± 0.008 min, respectively. The linear ranges for carbocisteine, guaifenesin, and oxomemazine were 31.25–187.50, 25–150, and 0.5–3.0 µg/mL, respectively. The developed method can be used in quality control laboratories for the simultaneous determination of the investigated drugs in their pharmaceutical dosage forms. In addition, it proved its superiority over the reported methods in terms of greenness using different assessment tools.

Determination of Gemcitabine and Sorafenib in Spiked Human Plasma Using Multivariate Model Update Chemometric Methods.

Gemcitabine (GEM), a pyrimidine nucleoside, has been used as a first-line treatment in non-small-cell lung cancer (NSCLC). Sorafenib (SOR), a nonselective multi-kinase inhibitor, is used as a chemotherapeutic agent in different types of cancers including NSCLC in preclinical studies. Co-administration of GEM and SOR was found to be effective and well-tolerated in the treatment of NSCLC. The aim of the present work is to determine the studied drugs in spiked human plasma simultaneously through resolving the overlapping spectra and removing the interference of the plasma matrix. Two updated chemometric models were developed using UV absorbance of the drugs, which named principal component regression (PCR) and partial least-squares (PLS) for determination of GEM and SOR in the ranges of 5-25 and 2-22 µg/mL, respectively. Validation of the two updated models has been achieved in accordance with US Food and Drug Administration (FDA) guidelines, and the results were satisfactory. The two methods had the advantages of high predictive ability of the studied drugs with high precision and accuracy. Moreover, there was no significant difference obtained when statistical comparison was done between the developed and reported methods, showing good validity of the suggested methods. The two updated models have the advantages of being rapid, accurate, sensitive, and cost-effective for the determination of GEM and SOR in quality control laboratories without any need for initial separation procedures. Two updated chemometric methods, PCR and PLS, were developed for the estimation of GEM and SOR in spiked human plasma using their UV absorbance data.

On-the-spot trace lactose test for flavored and unflavored lactose-free dairy beverages

We previously reported a novel Bioluminescence Resonance Energy Transfer (BRET)-based biosensing construct able to estimate trace levels of lactose (>0.01% (w/v)), directly in lactose-modified white milk, without the need for sample pre-treatment. In that study, the method was performed by highly trained researchers using a BRET-capable microplate reader in a research laboratory. It is desirable for the method to be adapted for on-the-spot use by production staff in a very different setting, the quality control lab of a milk processing factory. In such a setting, there is a growing requirement to produce and quality-control lactose-modified milks that are colored and flavored. Measurement of trace lactose in these matrices presents additional challenges over white milk because colors, flavors and added sugars potentially interfere with existing electrochemical or colorimetric biosensors. In the current work we therefore describe the development and validation of a method that uses the aforementioned BRET-based lactose biosensing construct to measure trace lactose in white, colored and flavored milks using a dedicated user-friendly device. Milk specific calibrations allowed the estimation of lactose at concentrations ranging from ≈ 7% (w/v) “full-lactose” to 0.01% (w/v), which is the most stringent quantified “lactose-free” level currently mandated globally. Limits of detection were 0.004% (w/v) for white milk and 0.003% (w/v) for both strawberry- and coffee-flavored milks. The assay could be performed in less than 5 min. We demonstrated the use of this assay to follow, effectively in real-time, simulated commercial lactase hydrolyses in white, strawberry- and coffee-flavored milks where the milk was aseptically incubated with food-grade lactase enzyme at 4 °C. These experiments highlighted the potential value of such a point-of-need lactose test for monitoring production, expediting release of finished product and accelerating new product development of a range of lactose-modified beverages.

Coupling of physical extraction and mathematical filtration in spectrophotometric analysis of natural therapy essential for prophylaxis and treatment of COVID-19 infection - Comparative study along with greenness evaluation

Diosmin (DIO) and hesperidin (HSP) are important classes of flavonoid glycoside effectively used to prevent comorbid diseases that are commonly associated with COVID-19. An innovative, green, ccurate, effective, cost, and timeless spectrophotometric strategy was established to analyze such challengeable mixture in a co-formulated tablet namely Diosed C® tablets that comprises DIO, HSP and vitamin C (VIT. C) in the ratio of (450 mg: 50 mg: 100 mg) necessary for prevention and treatment of COVID-19. Vitamin C was resolved through physical extraction using de-ionized water while DIO and HSP were extracted via spectrophotometric methods using two different solvents [0.1 M NaOH or solvent blend consisting of DMSO and methanol (1:1)]. Mathematical filtration technique is successfully applied to recover the parent spectra of both DIO and HSP via three methods which are absorbance resolution (AR), Induced absorbance resolution (IAR) and ratio extraction (RE). VIT. C was successfully analyzed in de-ionized water using its maxima at 266.0 nm in a linearity range 2.0–20.0 μg/mL, DIO was effectively determined in 0.1 M NaOH at 372.0 nm in a linearity range of 7.0–70.0 μg/mL as well as in solvent blend at 344.0 nm in linearity range of 5.0–55.0 μg/mL while HSP was accurately analyzed in 0.1 M NaOH at 240.0 nm in linearity range of 3.5–50.0 μg/mL as well as in solvent blend at 285.0 nm in linearity range of 4.0–50.0 μg/mL. Satisfactory results were accomplished when conducting ICH guidelines for assuring the methods validation. Comparative study was introduced in the analysis of such critical combination and was prosperously devoted for the effective analysis of pharmaceutical dosage form. The proposed extraction pathways undergo the guidelines of green analytical chemistry using Analytical Eco-Scale (AES), AGREE and GAPI greenness assessment tools which confirmed their eco-friendly nature with priority to 0.1 M NaOH. The obtained results of the suggested methods were set side by side with those of official/reported methods statistically and show satisfactory implications. The presented methods were simple, affordable, smoothly applicable and their results were acceptable that enhances their usage and application in the quality control laboratories.

Preparation and evaluation of certified reference materials for crude protein, crude fat, and crude ash in feed

Three new certified reference materials (CRMs) for crude protein, crude fat, and crude ash in animal feed were developed and characterized according to ISO 17034:2016 and ISO Guide 35:2017. The Kjeldahl, Soxhlet extraction, and ashing methods were employed to quantify these three components in candidate CRMs for swine feed, poultry feed, and fish feed. To improve the precision, the measurement methods were optimized on the basis of Directive 93/28/EEC, Directive 98/64/EC, and Directive 71/250/EEC and further validated using two existing CRMs (BCR-708 and BCR-709). The homogeneity, short- and long-term stability, and moisture content were evaluated. The certified values and their expanded uncertainties (k = 2.00) were determined through nine laboratories. The results for crude protein, crude fat, and crude ash were 14.7 ± 0.4, 5.19 ± 0.24, and 6.23 ± 0.14% for swine feed CRM; 22.7 ± 0.7, 5.16 ± 0.39, and 5.74 ± 0.18% for poultry feed CRM; and 35.6 ± 0.9, 9.29 ± 0.40, and 8.70 ± 0.25% for fish feed CRM, respectively. These three CRMs have been used in the comparison of Chinese feed quality testing laboratory systems and proved suitable for evaluating quality control in laboratories.

Green spectrophotometric method for the spectral pattern recognition based on fuzzy inference system compared to continuous wavelet transform for the quantitative determination of anti-psoriasis drugs in commercial skin ointment formulation: Comparison with HPLC

In this study, two chemometrics methods, including fuzzy inference system (FIS) along with principal component analysis (PCA) and continuous wavelet transform (CWT) were proposed for the simultaneous spectrophotometric estimation of betamethasone dipropionate (BMD) and calcipotriol (CP) in pharmaceutical dosage form without any pretreatment. The mean recovery and root mean square error (RMSE) related to the nine rules of the FIS was 100.14%, 100.72% and 0.016 and 0.020 for BMD and CP, respectively. CWT with wavelet families of Daubechies (db2) and Coiflet (Coif2) were selected to give the best zero crossing point at a wavelength of 254 nm and 265 nm, as well as the highest coefficient of determination (R2) for BMD and CP, respectively. The limit of detection (LOD) and limit of quantitation (LOQ) were found to be 5 × 10−5, 1.7 × 10−3 μg/mL and 0.0277, 0.0225 μg/mL through the calibration graphs in the linear concentration ranges of 1–10 μg/L for BMD and CP, respectively. The selected wavelet families were successfully applied for chemometric analysis of BMD and CP in synthetic mixtures with satisfactory mean recovery values of 94.67% and 102.43% for BMD and CP, respectively. The proposed spectrophotometric methods were statistically compared to high-performance liquid chromatography (HPLC) using analysis of variance (ANOVA). The proposed analytical techniques were found to be easy, fast, precise, and robust with less solvent consumption for the concurrent analysis of BMD and CP, which can be used instead of chromatography methods in pharmaceutical quality control laboratories.

Technical considerations for the implementation of the multi-attribute-method by mass spectrometry in a quality control laboratory

Multi-attribute methods employing mass spectrometry are applied throughout the biopharmaceutical industry for product and process characterization purposes but are not yet widely accepted as a method for batch release and stability testing under good manufacturing practice (GMP) due to limited experience and level of comfort with the technical, compliance and regulatory aspects of its implementation at quality control (QC) laboratories. Here, current literature related to the development and application of the multi-attribute method by peptide mapping liquid chromatography mass spectrometry (MAM) is compiled with the aim of providing guidance for the implementation of MAM in a QC laboratory. This article, focusing on technical considerations, is the first part of a two-tiered publication, whereby the second part will focus on GMP compliance and regulatory aspects. This publication has been prepared by a group of industry experts representing 14 globally acting major biotechnology companies under the umbrella of the European Federation of Pharmaceutical Industries and Associations (EFPIA) Manufacturing & Quality Expert Group (MQEG).

Trapping mode two-dimensional liquid chromatography for quantitative low-level impurity enrichment in pharmaceutical development

Trapping mode two-dimensional liquid chromatography (2D-LC) has recently found applications in pharmaceutical analysis to clean, refocus, and enrich analytes. Given its enrichment capability, 2D-LC with multiple trappings is appealing for low-level impurity monitoring that cannot be solved by single dimensional LC (1D-LC) or unenriched 2D-LC analysis. However, the quantitative features of multi-trapping 2D-LC remain largely unknown at impurity levels from parts-per-million (ppm) to 0.15% (w/w). We present a simple heart-cutting trapping mode 2D-LC workflow using only common components and software found in typical off-the-shelf 1D-LC instruments. This robust, turn-key system's quantitative capabilities were evaluated using a variety of standard markers, demonstrating linear enrichment for up to 20 trapping cycles and achieving a recovery of over 97.0%. Next, the trapping system was applied to several real-world low-level impurity pharmaceutical case studies including (1) the identification of two unknown impurities at sub-ppm levels resulting in material discoloration, (2) the discovery of a new impurity at 0.05% (w/w) co-eluted with a known impurity, making the undesired summation above the target specification, and (3) the quantification of a potential mutagenic impurity at 10-ppm level in a poorly soluble substrate. The recovery in all studies was better than 97.0% with RSD lower than 3.0%, demonstrating accuracy and precision of the 2D-LC trapping workflow. As no specialized equipment or software is required, we envision that the system could be used to develop low-impurity monitoring methods suitable for validation and potential execution in quality-control laboratories.

Charge Transfer Complex of Lorlatinib with Chloranilic Acid: Characterization and Application to the Development of a Novel 96-Microwell Spectrophotometric Assay with High Throughput.

Lorlatinib (LRL) is the first drug of the third generation of anaplastic lymphoma kinase (ALK) inhibitors used a first-line treatment of non-small cell lung cancer (NSCLC). This study describes, for the first time, the investigations for the formation of a charge transfer complex (CTC) between LRL, as electron donor, with chloranilic acid (CLA), as a π-electron acceptor. The CTC was characterized by ultraviolet (UV)-visible spectrophotometry and computational calculations. The UV-visible spectrophotometry ascertained the formation of the CTC in methanol via formation of a new broad absorption band with maximum absorption peak (λmax) at 530 nm. The molar absorptivity (ε) of the complex was 0.55 × 103 L mol-1 cm-1 and its band gap energy was 2.3465 eV. The stoichiometric ratio of LRL/CLA was found to be 1:2. The association constant of the complex was 0.40 × 103 L mol-1, and its standard free energy was -0.15 × 102 J mole-1. The computational calculation for the atomic charges of an energy minimized LRL molecule was conducted, the sites of interaction on the LRL molecule were assigned, and the mechanism of the reaction was postulated. The reaction was adopted as a basis for developing a novel 96-microwell spectrophotometric method (MW-SPA) for LRL. The assay limits of detection and quantitation were 2.1 and 6.5 µg/well, respectively. The assay was validated, and all validation parameters were acceptable. The assay was implemented successfully with great precision and accuracy to the determination of LRL in its bulk form and pharmaceutical formulation (tablets). This assay is simple, economic, and more importantly has a high-throughput property. Therefore, the assay can be valuable for routine in quality control laboratories for analysis of LRL's bulk form and pharmaceutical tablets.

Fluorescence imaging approaches for eco-friendly determination of perampanel in human plasma and application for therapeutic drug monitoring.

Antiepileptic drugs are among the most common medications that require therapeutic drug monitoring (TDM). Indeed, TDM provides a realistic approach to adjust drug doses for epilepsy based on plasma concentrations to optimize its clinical outcome. The most common technique for TDM is high-performance liquid chromatography, which has a very low green profile among analytical techniques. Perampanel (PER) is an inherently fluorescent compound that its fluorophore readily allows sensitive and quantitative measurements. This paper describes the development and validation of a sensitive, specific, and eco-friendly spectrofluorimetric method for the determination of PER. Experimental parameters affecting fluorescence intensity of the compound, including solvent dilution, temperature, and excitation wavelength, were studied and optimized. The developed spectrofluorimetric method was established in acetonitrile at λex = 295 nm and λem = 431 nm over a concentration range of 5-60 ng/ml. The adopted method was applied for the determination of PER in human plasma; it was effective in the range of 15-50 ng/ml. The proposed method was found to be sensitive and specific for PER and can be applied successfully in TDM of PER and in quality control laboratories.

Estimation of purity of antimicrobial lead compound sulfonamide-anthranilate derivative methyl-ester-toluene-sulfonamide using LC to develop a new drug application.

The newly synthesized lead molecule methyl-ester-toluene-sulfonamide is the combined derivative of sulfonamide-anthranilate. It was estimated by gradient elution using 0.1% triethylamine in water with pH2.0 as mobile phase A and the mixture of acetonitrile and tetrahydrofuran in the ratio of 975:25 (v/v) as mobile phase B at a flow rate of 0.8ml/min and 210 nm wavelength on an Agilent 1260 infinity series HPLC system equipped with a diode array detector. The column used was ACE 3 C18-PFP (250 × 4.6mm, 3μm i.d.) operating at 40°C. The gradient program was time (min)/% B: 0.0/50, 3.0/50, 15.0/70, 25.0/90, 30.0/90, 31/50, and 38/50. The method is simple, accurate, rapid, and selective. The method was linear with a concentration range of 1.6-240 μg/ml. The accuracy data obtained were 98.5-100.5%. The method validation data and quality by design-based robustness study results indicate that the developed method is robust and fit for routine use in the quality control laboratory. Therefore, the ready availability of the method can be useful in pharmaceutical new drug development.

Evaluasi Kontrol Kualitas Pemeriksaan Glukosa Darah di Laboratorium X Palangka Raya

Quality Control is a managerial procedure to adjust the laboratory examination (analytic) stages and detect errors early. The purpose of this study was to describe the quality control in laboratory X in the city of Palangka Raya. The method used is the descriptive method. The results showed that in April 2022, the Mean (88,1 mg/dL), SD (1,09 mg/dL), CV (1,24%), d (0,14%), TE (2,62%), TEa (10%), Sigma (7,94), and in May 2022 the Mean (87,9 mg/dL), SD (1,00 mg/dL), CV (1,13%), d (0,04%), TE (2,31%), TEa (10%), Sigma (8,79). According to the Ministry of Health, the maximum CV value is < 5%, so the inspection results of control materials in April 2022 and May 2022 are good or thorough. The maximum d value according to ISO 15179 is < 5%, so the inspection results of control materials in April 2022 and May 2022 are good or accurate. The evaluation of the control material with the Levey Jennings chart showed that all values in April 2022 and May 2022 were within the control limits, and none were outside the limits of the Westgard Mulrirule System rules. The result shows that the internal quality control activities of clinical chemistry for glucose parameters in Laboratory X are well executed and reliable.

Greenness Assessment of HPLC Analytical Methods with Common Detectors for Assay of Paracetamol and Related Materials in Drug Products and Biological Fluids

Paracetamol is one of the most widely consumed analgesic and antipyretic medications worldwide. It is frequently analyzed in many quality control (QC) laboratories in pharmaceutical companies, either in raw materials or drug products. It was reported that paracetamol self-toxicity often occurs, leading to the frequent analysis of paracetamol in toxicological centers in biological fluids. Green analytical chemistry (GAC) is growing to be a global philosophy; therefore, the high frequency of paracetamol analysis poses potential concerns. Chromatographic analytical methods used for the daily analysis of paracetamol could be a potential risk to the environment or the health of the analysts if not thoroughly considered. The presented study aims to establish greenness assessments of nine HPLC methods used to assay paracetamol in raw materials and drug products and twenty-one HPLC methods. The reason for selecting HPLC methods of analysis to be the core of the study is the known reproducibility, reliability and availability in most QC laboratories. The most commonly used metric systems for greenness evaluation are the Analytical GREEnness (AGREE), the eco-scale assessment (ESA) and the national environmental methods index (NEMI) which have been used in this comparative study. The greenest chromatographic method for the analysis of paracetamol in raw materials and drug products was introduced by Rao et al. (the obtained scores were ESA = 76 and AGREE = 0.62, while the greenest chromatographic method for the analysis of paracetamol in biological fluids was proposed by Modick et al.). The obtained scores were ESA = 85 and AGREE = 0.7. The NEMI tool proved to have limited performance compared to other metric systems, hence it could not be used alone. Accordingly, the collaboration of NEMI results with ESA and AGREE for greenness assessment is highly recommended to reach appropriate conclusions.

The Role of Surveillance Inspections in Reducing False-Positives of SARS-CoV-2 Omicron Variants during the COVID-19 Epidemic.

This study aims to assess the effectiveness of surveillance inspections conducted by the provincial health committee in Quanzhou city during a COVID-19 outbreak in reducing false-positive results in SARS-CoV-2 RT-PCR assays. The team conducted on-site inspections of laboratories that participated in mass screening, recording any violations of rules. The positive cases in five rounds of mass screening were 23, 173, and 4 in Licheng District, Fengze District, and Luojang District, respectively. The false-positive rates in the five rounds of mass screening were 0.0099%, 0.0063%, 0.0018%, 0.0006%, and 0%, respectively. The study also recorded that the number of violations in the seven selected laboratories was 36, 68, 69, 42, 60, 54 and 47. The corresponding false-positive rates were 0.0012%, 0.0060%, 0.0082%, 0.0032%, 0.0060%, 0.0027%, and 0.0021%, respectively. The study found a positive correlation between false-positive rates and the number of violations (r = 0.905, P=0.005), and an inverse correlation between false-positive rates and the frequency of surveillance inspections (r = -0.950, P < 0.001). Daily surveillance inspection in laboratories can remind laboratories to strictly comply with standard procedures, focus on laboratory quality control, and reduce the occurrence of false-positive cases in SARS-CoV-2 nucleic acid tests to some extent. This study recommends that government decision-making departments establish policies and arrange experts to conduct daily surveillance inspections to improve laboratory quality control.

Spectrophotometric Investigations of Charge Transfer Complexes of Tyrosine Kinase Inhibitors with Iodine as a σ-Electron Acceptor: Application to Development of Universal High-Throughput Microwell Assay for Their Determination in Pharmaceutical Formulations.

Background and Objective: Tyrosine kinase inhibitors (TKIs) are used for the treatment of different types of cancers. The current study describes, for the first time, the ultraviolet-visible spectrophotometric investigation of charge transfer complexes (CTCs) of seven TKIs, as electron donors, and iodine, as σ-electron. Materials and Methods: The formation of CTCs was promoted in dichloromethane, among the other solvents used in the investigation. The molar absorptivity values, association constants, and free energy changes of the CTCs were determined. Stoichiometric ratio of TKI: iodine as well as TKIs site(s) of interaction were addressed. Reaction was the basis for constructing a novel simple and accurate 96-microwell spectrophotometric assay (MW-SPA) with high-throughput property for the quantitative determination of TKIs in their pharmaceutical formulations. Results: Beer's law, which relates CTC absorbances to TKI concentrations, was followed within the optimal range of 2 to 100 µg/well (r ranged from 0.9991 to 0.9998). Detection and quantification limits ranged from 0.91 to 3.60 and 2.76 to 10.92 g µmL-1, respectively. Relative standard deviations values for the intra- and inter-assay precisions of the proposed MW-SPA did not exceed 2.13 and 2.34%, respectively. Studies of recovery demonstrated MW-SPA accuracy, with results ranging from 98.9% to 102.4%. All TKIs, both in bulk form and in pharmaceutical formulations (tablets), were effectively determined using the suggested MW-SPA. Conclusions: The current MW-SPA involved a simple procedure and it was convenient as it could analyse all proposed TKIs utilizing a single assay system at once measuring wavelengths for all TKIs. In addition, the proposed MW-SPA has high throughput which enables the processing of a batch of huge samples' number in very short reasonable time period. In conclusion, TKIs can be routinely analysed in their dosage forms in quality control laboratories, and the assay can be highly valuable and helpful in this regard.

РАЗРАБОТКА РАЗЛИЧНЫХ ВИДОВ ЦЕМЕНТОВ ДЛЯ УСТРОЙСТВА КОНСТРУКТИВНЫХ СЛОЕВ ДОРОЖНОЙ ОДЕЖДЫ НА ОСНОВЕ АСФАЛЬТОГРАНУЛОБЕТОННЫХ СМЕСЕЙ

Today, the highway is not just a construction site, but also an important component in the structure of the country's economic development. Recently, transport loads on the structural layer of pavement have increased many times over as a result of an increase in freight turnover on the roads of the automobile network. To maintain the operational reliability of roads and extend their life cycle, high-quality and innovative materials are needed, technological modes of work adapted to them, as well as timely laboratory research, quality control and monitoring of materials being developed. This will improve the physical and mechanical properties of materials used in the construction of pavement structural layers. One effective approach is to reinforce the pavement base using cement based asphalt granular concrete mix (AGC), which involves the recycling of local materials instead of expensive stone materials. In the work, studies were carried out on the effect of a binder based on NLMK PJSC granulated blast-furnace slag, modified with various chemical additives, on the physical and mechanical properties of the asphalt granular concrete mixture. The effectiveness of the developed compositions lies in the fact that the slag becomes more hydraulically reactive not as a result of activation with caustic alkali or other low-modulus soluble silicates, but due to the use of special reagents that do not adversely affect process equipment and workers. Moreover, the annual growth of carbon dioxide emissions into the atmosphere in the production of cement expands the need for the use of alternative types of binders in construction. It has been established that samples of AGBS-K type asphalt-granular concrete mixture based on the developed compositions of an inorganic binder exceed the strength characteristics of composites using cement.

Novel High-Throughput Microwell Spectrophotometric Assay for One-Step Determination of Lorlatinib, a Novel Potent Drug for the Treatment of Anaplastic Lymphoma Kinase (ALK)-Positive Non-Small Cell Lung Cancer.

Background and Objectives: Lorlatinib (LOR) belongs to the third-generation anaplastic lymphoma kinase (ALK) tyrosine kinase inhibitors. People who are diagnosed with ALK-positive metastatic and advanced non-small cell lung cancer (NSCLC) are eligible to get it as a first-line treatment option after it was given the approval by "the Food and Drug Administration (FDA)". However, no study has described constructing high-throughput analytical methodology for LOR quantitation in dosage form. For the first time, this work details the construction of a high-throughput, innovative microwell spectrophotometric assay (MW-SPA) for single-step assessment of LOR in its tablet form, for use in pharmaceutical quality control. Materials and Methods: Assay depended on charge transfer complex (CTC) formation between LOR, as electron donor, with 2,3-dichloro-3,5-dicyano-1,4-benzoquinone (DDQ), as π-electron acceptor. Reaction conditions were adjusted, the CTC was characterized by ultraviolet (UV)-visible spectrophotometry and computational molecular modeling, and its electronic constants were determined. Site of interaction on LOR molecule was allocated and reaction mechanism was suggested. Under refined optimum reaction conditions, the procedures of MW-SPA were performed in 96-well assay plates, and the responses were recorded by an absorbance plate reader. Validation of the current methodology was performed in accordance with guidelines of "the International Council on Harmonization (ICH)", and all validation parameters were acceptable. Results: Limits of detection and quantitation of MW-SPA were 1.8 and 5.5 µg/well, respectively. The assay was applied with great success for determining LOR in its tablets. Conclusions: This The assay is straightforward, economic and has high-throughput characteristics. Consequently, the assay is recommended as a valuable analytical approach in quality control laboratories for LOR's tablets' analysis.

Development of Different Separation Techniques for Impurity Profiling of Neostigmine Methylsulfate: A Comparative Study.

Different separation techniques have been employed to resolve mixtures of multicomponent preparations over the last few decades. They could be efficiently applied for impurity profiling of active drug substances. Impurity profiling has become a critical procedure in pharmaceutical companies to comply with numerous regulatory standards. Isolation and characterization of impurities are crucial for obtaining data that proves biological safety and efficacy. In this contribution, different HPLC, capillary electrophoresis (CE) and TLC-densitometric methods were developed for the determination of neostigmine methylsulfate (NEO) along with 3-hydroxyphenyltrimethyl ammonium methylsulfate (3-HPA) and 3-dimethylaminophenol (DAP) as its impurities in the presence of citric acid. The linearity for NEO was attained in the range of 5-120μg/mL and 10-60μg/mL for the HPLC and CE methods, respectively. Regarding the impurities, linearity was obtained over the range of 10-30μg/mL for 3-HPA and 5-30μg/mL for DAP in the two proposed methods. For the TLC method, NEO and DAP were determined within the range of 1-11μg/band, whereas 3-HPA was assayed over the range of 2-12μg/band. The suggested methods can be securely utilized for routine analysis of the cited components in quality control laboratories.

Application of ISO 17025 Standards in the Validation of a Spectrophotometric Method for Quality Assessment of Generic Brands of Cetirizine Tablets marketed in Nigeria.

Background: The concern for the quality of medicines is to ensure effiffifficacious clinical outcomes and quality health care. The World Health Organization (WHO) estimates that 10–20 % of medicines in&nbsp;developing country markets are sub-standard. Continuous&nbsp; monitoring of the quality of medicines&nbsp;requires both competent analysts and well-equipped drug quality control laboratories with&nbsp;&nbsp;international accreditation. The objective of the study was to evaluate the quality control parameters of&nbsp;the generic cetirizine&nbsp; dihydrochloride 10 mg tablets marketed in Abuja metropolis of Nigeria and to&nbsp;validate and apply a UV spectrophotometric method to&nbsp; the assay of the commercial tablet&nbsp;formulations.&nbsp; Method: Nine brands of cetirizine dihydrochloride tablets were randomly selected from retail&nbsp;pharmacy stores and quality control&nbsp; tests of weight variation, friability, hardness, disintegration, and&nbsp;dissolution parameters were conducted per United States&nbsp; Pharmacopoeia (USP) standards. Thickness&nbsp;and diameter were also evaluated by standard methods. AUVspectrophotometric method&nbsp; was adopted&nbsp;and validated according to ICH guidelines and applied for the drug assay of the tablet dosage units.&nbsp; Results: The&nbsp; thickness, diameter, hardness and disintegration tests for the drug samples ranged from&nbsp;2.81–3.76 mm, 3.88–8.11 mm&nbsp; 1.65–7.50 KgF and 0.44–4.90 min, respectively. All the samples met the&nbsp;compendial specififications for the weight variation test and also&nbsp; for the friability and dissolution tests&nbsp;which ranged 0.18–0.56 % and 90.15–109.18 % at 30 min, respectively. The studies for&nbsp; validation of&nbsp;the UV method demonstrated good linearity with a correlation coeffiffifficient of r2 = 0.9989 in the&nbsp;concentration range of&nbsp; 2.5–25 µg/mL of cetirizine dihydrochloride (CTZ) reference standard and the&nbsp;limit of detection (LOD) and limit of quantitation (LOQ)&nbsp; were 0.42 µg/mL and 1.29 µg/mL,&nbsp;respectively. The % RSD of the precision studies was less than the 2 % standard limit and the&nbsp; accuracy&nbsp;(recovery) ranged from 100.9‒103.4 %. The percentage contents of the generic brands were&nbsp;determined and ranged from&nbsp; 99.12–103.21 % and were within the offiffifficial specififications.&nbsp; Conclusion: The UV method was simple, sensitive and rapid and&nbsp; successfully applied to the assay of&nbsp;nine commercial brands of CTZ&nbsp; tablets. All the drugs met the compendial specififications on the quality&nbsp;parameters.&nbsp;&nbsp