International Conference On Harmonization Research Articles

Non-destructive Raman Method Development for Quantifying Active Pharmaceutical Ingredient in an Oral Suspension Through Plastic Dosing Syringes.

For liquid drug products, e.g., solutions or suspensions for oral or parenteral dosing, stability needs to be demonstrated in primary packaging during storage and in dosing devices during in-use periods per quality guidelines from the International Conference on Harmonisation (ICH) and the European Agency for the Evaluation of Medicinal Products (EMEA). One aspect of stability testing for liquid drug products is in-use stability, which typically includes transferring the liquid samples into another container for further sample preparation with extraction diluent and necessary agitation. Samples are then analyzed with traditional chromatography methods, which are laborious, prone to human errors, and time-consuming, especially when this process needs to be repeated multiple times during storage and in-use periods. Being able to analyze the liquid samples non-destructively would significantly improve testing efficiency. We investigated different Raman techniques, including transmission Raman (TRS) and back scatter Raman with a non-contact optic (NCO) probe, as alternative non-destructive tools to the UHPLC method for API quantitation in in-use liquid samples pulled into plastic dosing syringes. The linearity of the chemometric methods for these two techniques was demonstrated by cross-validation sample sets at three levels over an API concentration range of 60 to 80 mg/mL. The accuracy of the chemometric models was demonstrated by the accurate prediction of the API concentrations in independent samples from four different pilot plant batches manufactured at different sites. Both techniques were successful in measuring a signal through a plastic oral dosing syringe, and predicting the suspension API concentration to within 4% of the UHPLC-measured value. For future work, there are opportunities to improve the methodology by exploring additional probes or to expand the range of applications by using different sample presentations (such as prefilled syringes) or formulation matrices for solutions and suspensions.

Antibiotic residues in pasteurised and Raw Cow’s milk in Dhaka, Bangladesh

ABSTRACT This study aimed to investigate antibiotic residues such as oxytetracycline, ciprofloxacin, enrofloxacin and levofloxacin, in both pasteurised and raw cow’s milk. A method using high-performance liquid chromatography with a UV detector (HPLC-UV) was developed and validated following International Conference on Harmonization (ICH) guidelines for simultaneous detection and quantification of these residues. The technique demonstrated linearity, with r2 values ranging from 0.999 to 1.00 within the 1.3–15.0 μg ml−1 range for each antibiotic. Thirty cow’s milk samples, raw and pasteurised, from Dhaka’s local markets were analysed, revealing the presence of enrofloxacin and levofloxacin, while oxytetracycline was absent in all samples. Notably, pasteurised milk samples contained enrofloxacin, levofloxacin and oxytetracycline, with groups P6 and P7 exceeding the Maximum Residue Limit for enrofloxacin, levofloxacin and ciprofloxacin (121 µg l−1). This study emphasises antibiotic residues in milk, with a validated method holding promise for routine analysis in industries requiring simultaneous quantitation of multiple antibiotics.

Validation of spectrophotometric methods for the simultaneous determination of fluconazole and riparin B in the development of lipid nanoparticles modified by β-cyclodextrin: Application for in vitro characterization and ex vivo studies of nail retention

Fluconazole (FLC) has been used in the clinic for almost thirty years as a treatment for fungal infections, but its widespread use has led to the emergence of resistant strains. In this context, synthetic analogues of riparins, phytocompounds isolated from Aniba riparia (Nees) Mez (Lauraceae), such as Riparin B (RIP), stand out as an important agent for modulating antimicrobial resistance, potentially useful for treating superficial mycoses resistant to conventional antifungals. Onychomycosis is one of the main fungal infections affecting the nails. Its local treatment is desirable but has limited efficacy due to poor drug permeation. The use of nanoparticles and permeation promoters can increase permeability and improve treatment. Therefore, nanostructured lipid carriers coated with β-cyclodextrin (MNLC) were developed for the topical application of FLC and RIP on nails. To support the formulation, four spectrophotometric methods (amplitude factor, amplitude subtraction, modified amplitude subtraction, and fourth-order derivative), based on derivative spectroscopy and simple mathematical manipulations, were validated, in accordance with the International Conference on Harmonization (ICH), for simultaneous determination of FLC and RIP in the MNLC and in in vitro characterization studies of the formulation. In addition, the methods were applied to quantify drug retention in porcine hooves using an optimized extraction process. All the methods developed were found to be linear (r > 0.999), precise (RSD < 5 %), and accurate (92.33 to 108.86 %) without being affected by the components of the formulation or the biological matrix. The methods developed made it possible to determine the encapsulation efficiency and sustained release profile of the drugs. In addition, successive extractions revealed the amount of FLC and RIP retained in the superficial and deeper regions of porcine hooves. Thus, the results indicated that FLC and RIP can be determined simultaneously, quickly, simply, and economically, using any of the proposed methods, in complex MNLC samples and the biological matrix of porcine hooves.

Green innovation in analytical chemistry: A sustainable densitometric HPTLC approach for the distinctive separation and quantification of structurally related abused drugs - tramadol, tapentadol, and venlafaxine - in seized pharmaceutical dosage forms

An innovative ecofriendly high-performance thin layer chromatographic (HPTLC) method with spectrophotometric detection for simultaneous determination of Tramadol (TMD), Tapentadol (TAP), and Venlafaxine (VEN) in seized dosage forms was presented. Our method was conducted to achieve separation following the optimal conditions: pre-coated silica gel plates using a green mobile phase (heptane: acetone: ammonia, 7:3:0.5 v/v), with absorbance scanning at 272 nm. The validation of the method was done following International Conference on Harmonization (ICH) guidelines, demonstrates linearity, accuracy, precision, selectivity, robustness, and system suitability. Separation was achieved with a detection limit of 0.34, 0.16, and 0.084 (ug/band) for TMD, TAP, and VEN, respectively, the method successfully analyzes seized samples. Trueness is confirmed through a high degree of similarity between HPTLC and gas chromatography results. The study's ecofriendly approach, simplicity, and selectivity position it as a promising method for efficient, on-site monitoring of seized samples.

A Novel Stability-Indicating RP-HPLC Method for the Simultaneous Estimation and In Vitro and In vivo Evaluation: Curcumin and Naringin Co-amorphous System

AbstractCurcumin (CUR) is a phytochemical widely used in food industries, cosmetics, and in the treatment of various ailments. It is a polyphenol derived from turmeric and is often considered the golden spice. CUR has a low solubility of less than 1 µg/ml and poor oral bioavailability which can be improved by co-amorphization with naringin (NRG). Analytical method to simultaneously quantify CUR and NRG is not reported in literature. This study aimed to develop a stability-indicating reverse phase HPLC method in gradient mode to simultaneously quantify CUR and NRG in co-amorphous system. The co-amorphous system of CUR and NRG in molar ratios 1:1 and 1:2 was prepared by quench cooling technique. The separation was attained on a Genesis C18, (4.6 mm × 150 mm, 4 µm) column with the mobile phase comprising of methanol and a 0.1% acetate buffer pH 3.8 at a single wavelength, 289 nm. CUR and NRG eluted at 5.1 and 11.1 min, respectively. For both the molecules, the linearity range was 0.125–16 µg/ml with LOD and LOQ of 0.063 and 0.125 µg/ml. The method developed was validated as per International Conference on Harmonization (ICH) guidelines for linearity, accuracy, precision, and robustness. The method was used to estimate CUR and NRG content in co-amorphous mixture and for in vitro evaluation. Graphical Abstract

Development And Validation Of Rp-Hplc Method For The Estimation Of Tenofovir And Emtricitabine In Bulk And Pharmaceutical Dosage Form.

A novel, simple, efficient, rapid, and precise reverse-phase high-performance liquid chromatography (RP-HPLC) method was developed for the estimation of Tenofovir and Emtricitabine in the bulk and pharmaceutical dosage form. The currently developed method was subsequently validated according to ICH guidelines in terms of linearity, accuracy, precision, the limit of detection, the limit of quantification, robustness, etc. Methods: The separation of the selected drugs was optimized after several trials including change of mobile phase and its composition, stationary phase, flow rate, column temperature, etc. The separation was performed by using an Inertsil ODS C18 column (250 mm x 4.6 mm, 5μ) and UV absorption was measured at 231 nm. Methanol: Acetonitrile: Water was selected as the mobile phase in the ratio of 50:20:30 (V/V/V) at a flow rate of 1 mL/min. As per International Conference on Harmonization (ICH) Q2 R1 guidelines, several validation parameters were evaluated which include specificity, linearity, precision, accuracy, the limit of detection (LOD), and the limit of quantitation (LOQ). The acceptable degree of linearity range was found to be 40-100 µg/mL. The standard solution exhibited retention times of 3.06 minutes and 5.07 minutes for Tenofovir and Emtricitabine respectively. The LOD and LOQ obtained were 0.05µg/ml and 0.02µg/mL, 15µg/mL, and 0.08µg/mL for Tenofovir and Emtricitabine respectively. The percent recovery was found to be 98 to 102%. Hence, the proposed method is simple, selective, and specifically meets the requirements of ICH guidelines for the validation of the analytical method.

Combined green analytical principles and quality by design for ultraperformance liquid chromatography analytical method development, the characterization and in-silico toxicity prediction of Ixazomib degradation products using mass spectrometry

Ixazomib citrate (IC) is the first oral selective proteosome inhibitor for treating multiple myeloma. IC is prone to degradation due to its oxidative deboronation and the amide bond, affecting patient health, drug quality, and efficacy. The stability of IC is crucial during drug development as it guides the inherent stability of the molecule, its degradation pathways, packing materials, and formulation development. Following the International Conference on Harmonization (ICH) Q1A (R2) and Q1B, a stability study were performed for both solution and solid-state stress studies. Under oxidative and alkaline conditions, 3 degradation products (DPs) were identified, separated, and method-validated according to ICH Q2 (R1) guidelines. From the Design Expert statistical tool, the Central Composite Design was used to optimize the final analytical method conditions, where the p-values for the model are < 0.05%. Green analytical chemistry has significantly reduced the use of hazardous organic solvents without losing chromatographic performance. The green separation and quantification of DPs and IC on Ultra Performance Liquid Chromatography (UPLC) using an Inert-Sustain C8 (50×3.0) mm 2.0 µm column with gradient elution using 10 mM ammonium acetate buffer (pH 5.0) and ethanol at a flow rate of 0.5 mL/min and detection at 230 nm. The results of green assessment tools like GAPI, AGREE, and Analytical eco-scale found that the method is excellent for the greenness of utilizing ethanol as a solvent, shorter runtime, and lesser waste. The method was validated as per ICH Q2 guidelines, and the results found it is sensitive, precise, accurate, robust, and linear for its intended use. The method is suitable for quantifying IC and its DPs from 2.0 to 150 µg/mL with R2 values of 0.9996 with a detection limit of 1.0 µg/mL. The plausible degradation structures and pathways of DPs were outlined using tandem mass spectra employed on LC-QTOF-MS/MS in both ESI positive and negative modes. The mechanistic explanation for establishing DPs was explained in detail. The ADMET Predictor™ software predicted the physicochemical and ADMET properties. The toxicity profile reveals that DP2 and DP3 are teratogenic, while D1 and D3 show phospholipidosis.

Quantitative Estimation of Mangiferin and Molecular Docking Simulation of Salacia reticulata Formulation

The phytochemical constituents present in herbal products need to be determined in their prescribed strength in order to ensure their efficacy and product quality in formulations. The marker-based standardization of herbal products is a well-accepted concept. In this study Mangiferin is used as marker to estimate the amount of Mangiferin present in the formulation Salacia Lin. Veggie capsules containing 400mg of Salacia reticulata extract to treat type 2 diabetes mellitus. The method was validated as per the international conference on harmonization (ICH) guidelines that is applicable in industry as well as in academia. The method was developed using reverse phase, Analytical column used for the separation of analytes, Phenomenex HPLC C18 (250 X 4.6 mm, 5 μm). The run time was of 7 min. The mobile phase used was acetonitrile and orthophosphoric acid (pH adjusted to 3.5) in the ratio 85:15 at a flow rate of 0.5ml/min, column temperature was maintained at 28°C and a detection wavelength of 257 nm using a photodiode array detector. The optimized method that was developed resulted in the elution of Mangiferin at 4.83min and % recovery was between 97.09 to 101.57. Molecular docking investigation was done using Schrodinger software. The binding affinity of phytoconstituents present in Salacia reticulata to intestinal enzymes alpha amylase was investigated to study their possible inhibitory mechanism. The physicochemical and drug-likeness properties of the phytoconstituents were evaluated. The phytoconstituent salacinol showed highest docking score (- 9.592) with alpha amylase (2QV4 obtained from protein data bank) and Mangiferin showed a score of -8.235 in comparison with standard acarbose ( -10.274). Studies showed phytoconstituents Mangiferin, Salacinol and Kotalanol can be potential inhibitors of 2QV4, and potent drug candidates for T2DM. However, further studies on these phytoconstituents should be carried out by wet lab experiments to prove their effectiveness.

Scientific Review of the Proarrhythmic Risks of Oligonucleotide Therapeutics: Are Dedicated ICH S7B/E14 Studies Needed for Low-Risk Modalities?

Oligonucleotide therapeutics (ONTs) represent a new modality with unique pharmacological and chemical properties that modulate gene expression with a high degree of target specificity mediated by complementary Watson-Crick base pair hybridization. To date, the proarrhythmic assessment of ONTs has been influenced by International Conference on Harmonization (ICH) E14 and S7B guidance. To document current hERG/QTc evaluation practices, we reviewed US Food and Drug Administration (FDA) and the European Medicines Agency (EMA) Approval Packages (source: PharmaPendium.com) and collated preclinical and clinical studies for 17 marketed ONTs. In addition, clinical QTc data from 12 investigational ONTs were obtained from the literature. Of the marketed ONTs, eight were tested in the hERG assay with no inhibitory effect identified at the top concentration (range: 34-3,000 μM) tested. Fourteen of the ONTs were evaluated in nonhuman primate cardiovascular studies with 11 of them in dedicated telemetry studies. No effect on QTc intervals were observed (at high exposure multiples) in all studies. Clinically, four ONTs were evaluated in TQT studies; an additional six ONTs were assessed by concentration-QTc interval analysis, and six by routine safety electrocardiogram monitoring. None of the clinical studies identified a QTc prolongation risk; the same was true for the 12 investigational ONTs. A search of the FDA Adverse Event Database indicated no association between approved ONTs and proarrhythmias. Overall, the collective weight of evidence from 29 ONTs demonstrate no clinical proarrhythmic risk based on data obtained from ICH S7B/E14 studies. Thus, new ONTs may benefit from reduced testing strategies because they have no proarrhythmic risk, a similar cardiac safety profile as monoclonal antibodies, proteins, and peptides.

Evaluation of iso-quinoline alkaloids by RP-HPLC-PDA in different Berberis species collected from Western Himalayan Region

The genus Berberis has high significance in Indian and other traditional systems of medicine due to the presence of iso-quinoline alkaloids. This study was conducted to record the metabolic variation in eight Berberis spp. collected from the Western Himalayan region. The RP-HPLC-PDA chromatogram separates the markers jatrorrhizine, palmatine and berberine at specific retention time, 11.45, 16.41 and 18.15 min respectively. The method was validated on linearity, precision and recovery indices as per International Conference on Harmonisation (ICH) guidelines. The maximum content of berberine, palmatine and jatrorrhizine was found in Berberis asiatica (1.74% ± 0.032, 1.63% ± 0.028 and 0.264% ± 0.012, respectively) on % dry weight basis. This study will help in phyto-marker-based identification and differentiation of various Berberis species, which can be used as an alternative to the official drug Daruharidra i.e. Berberis aristata.

Development of a Stability Indicating UPLC Method for the Determination of Tirbanibulin in Bulk and Its Pharmaceutical Dosage Form.

The primary goal of this study was to create and validate a simple, precise, sensitive, and accurate ultra-performance liquid chromatography (UPLC) method for estimating tirbanibulin in pure and dosage form. A UPLC technique was developed using a Waters Acquity UPLC Phenyl (100 x 2.1 mm, 1.7 µm) column. The developed technique was validated in accordance with the International Conference on Harmonization (ICH) guidelines. Tirbanibulin was separated chromatographically with high resolution using the mobile phase acetonitrile: buffer (30:70 v/v) at 0.5 mL/min, 5 µL injection volume, and 220 nm wavelength. The validated technique was found to be linear in the 1-15 µg/mL range. The detection and quantification limits for tirbanibulin were 0.03 and 0.1 µg/mL, respectively. The percentage relative standard deviation was less than 2%, demonstrating the precision of the developed technique. Furthermore, the recovery rate was nearly 100%, confirming the accuracy of the method. Minor modifications to the chromatographic conditions demonstrated the robustness of the method. The developed analytical method was precise, simple, reproducible, and sensitive. Consequently, it can be used to determine tirbanibulin.

Stress degradation study of Etoricoxib, isolation, and characterization of major degradation impurity by preparative high‐performance liquid chromatography, liquid chromatography‐mass spectrometry, and nuclear magnetic resonance: Validation of ultra‐performance liquid chromatography method

AbstractEtoricoxib (ETO) is a selective cyclooxygenase‐2 inhibitor, used as a nonsteroidal anti‐inflammatory drug. In this study, a detailed investigation was conducted on the degradation behavior of ETO under acidic, basic, neutral, photolytic, oxidative, and thermal degradation conditions as per the International Conference on Harmonization (ICH) guideline Q1A (R2). A gradient “ultra‐performance liquid chromatography (UPLC)” method was developed for separating the degradation products formed under various degradation conditions along with process‐related impurities. Acquity BEH phenyl column was used for the separation of analytes and 0.1% formic acid in water and 0.05% formic acid in acetonitrile:methanol (8:2 %v/v) were used as mobile phase‐A and mobile phase‐B. A major degradant namely, N‐oxide impurity was observed in oxidative degradation along with two minor degradants where N‐oxide was confirmed based on LC‐mass spectrometry (LC‐MS) studies. Further, the major degradant was enriched and isolated using preparative HPLC and the conformation of the N‐oxide impurity was established using nuclear magnetic resonance techniques including two‐dimensional studies and high‐resolution MS. In addition, the method for related substances by UPLC has been validated by considering a major degradant, namely N‐oxide along with process‐related impurities as per the ICH guidelines validation parameters.

Application of FTIR Spectroscopy method for The Quantification of Ascorbic Acid in Bulk Materials and Pharmaceutical Formulation

The present study illustrates the potential using of Fourier Transform Infrared Spectroscopy (FT-IR) in pharmaceutical analysis. A simple, rapid, non-destructive, and green (FT-IR) spectroscopy method for quality control evaluation of Ascorbic acid was developed, using potassium bromide (KBr) as a matrix to quantify the drug in bulk pharmaceutical materials and AUC its dosage forms. The sample preparation was done by mixing and grinding for disk composition and without using organic solvents. Absorbance obtained for the carbon-carbon band (C=C) located at the range (1600-1700) cm-1 was used to develop a calibration curve based on the AUC measurements. Method had been validated according to the International Conference on Harmonization (ICH) guidelines. Linearity, accuracy, precision, robustness, LOD and LOQ were evaluated and showed acceptable results for method validation in the concentration range of (2 - 12.5 mg). The validated method was able to apply for the quality control analysis of Ascorbic Acid raw materials and pharmaceutical dosage forms.

Development of a high-performance thin-layer chromatography-based method for targeted glycerolipidome profiling of microalgae

The conditionally essential very-long-chain polyunsaturated fatty acids (VLC-PUFAs), such as eicosapentaenoic acid (EPA, C20:5 n-3), play a vital role in human nutrition. Their biological activity is thereby greatly influenced by the distinct glycerolipid molecule that they are esterified to. Here, microalgae differ from the conventional source, fish oil, both in quantity and distribution of VLC-PUFAs among the glycerolipidome. Therefore, the aim of this study was to develop a fast and reliable one-dimensional high-performance thin-layer chromatography (HPTLC)-based method that allows the separation and quantification of the main microalgal glycerolipid classes (e.g., monogalactosyldiacylglycerol (MGDG), sulfoquinovosyl diacylglycerol (SQDG), phosphatidylglycerol (PG)), as well as the subsequent analysis of their respective fatty acid distribution via gas chromatography (GC) coupled to mass spectrometry (MS). Following optimization, method validation was carried out for 13 different lipid classes, based on the International Conference on Harmonization (ICH) guidelines. In HPTLC, linearity was effective between 100 and 2100 ng, with a limit of quantification between 62.99 and 90.09 ng depending on the glycerolipid class, with strong correlation coefficients (R2 > 0.995). The recovery varied between 93.17 and 108.12%, while the inter-day precision measurements showed coefficients of variation of less than 8.85%, close to the limit of detection. Applying this method to crude lipid extracts of four EPA producing microalgae of commercial interest, the content of different glycerolipid classes was assessed together with the respective FA distribution subsequent to band elution. The results showed that the described precise and accurate HPTLC method offers the possibility to be used routinely to follow variations in the glycerolipid class levels throughout strain screening, cultivation, or bioprocessing. Thus, additional quantitative analytical information on the complex lipidome of microalgae can be obtained, especially for n-3 and n-6 enriched lipid fractions.Graphical

A Review on The Impurity Profile of Pharmaceuticals

A collection of analytical procedures known collectively as “impurity profiling” are intended to detect, identify, clarify the structure of, and quantify both organic and inorganic impurities as well as residual solvents in pharmaceutical formulations and bulk pharmaceuticals. This is the main task of contemporary drug analysis since it is the most effective approach to describe the stability and quality of pharmaceutical formulations and bulk pharmaceuticals. To keep an eye on them, specific analytical techniques must be created. When modifications are made to the synthesis, formulation, or production processes, even if they are done to improve them, new purities could be seen. The identification of impurities in Active Pharmaceutical Ingredients (APIs) and the need for purity are being emphasised by a number of regulatory bodies, including the Canadian Drug and Health Agency (CDHA), the United States Food and Drug Administration (FDA), and the International Conference on Harmonisation (ICH). Pharmaceutical products can contain impurities from a variety of sources, including reagents, heavy metals, ligands, catalysts and other materials like charcoal, filter aids, and the like. Degraded end products from hydrolysis, photolytic cleavage, oxidative degradation, decarboxylation, and other processes can also contain impurities, as can enantiomeric impurities. The various pharmacopoeias, including the Indian, American, and British pharmacopoeias, are gradually adding restrictions to the permissible concentrations of contaminants found in APIs or formulations. Capillary electrophoresis, electron paramagnetic resonance, gas-liquid chromatography, gravimetric analysis, high performance liquid chromatography, solidphase extraction techniques, liquid-liquid extraction techniques, mass spectrometry, ultraviolet spectrometry, infrared spectroscopy, supercritical fluid extraction column chromatography, nuclear magnetic resonance (NMR) spectroscopy, and RAMAN spectroscopy are some of the techniques used to isolate and characterize impurities in pharmaceuticals. Liquid Chromatography (LC)-Mass Spectroscopy (MS), GC-MS, LC-NMR, LC- NMR-MS, and LC-MS are the most frequently used hyphenated techniques for drug impurity profiling. This demonstrates the importance and range of drug impurity profiling in pharmaceutical research.

A new green fluorimetric micelle complexation approach for reduction of the consumed solvent and quantification of avapritinib in biological fluids.

Avapritinib (AVA) is the first medication authorized by the US-FDA in 2020 for the management of gastrointestinal stromal tumours (GISTs) that can't be treated by surgery. Cancer is among the most common causes of death worldwide and is the second most common cause of death after cardiovascular disease. Therefore, a quick, easy, sensitive, and straightforward fluorimetric approach was used to analyse AVA in pharmaceutical materials and blood plasma (pharmacokinetic). The suggested technique relies on 2% sodium dodecyl sulphate (SDS, pH 4) micellar system augmentation of the fluorescence of the tested drug. The technique demonstrated high relative fluorescence intensity (RFI) at 430 nm after excitation at 340 nm. Concentrations ranging from 20.0-400.0 ng mL-1 with a limit of quantitation of 9.47 ng mL-1 were used to obtain luminescence data for the studied medicine. In addition, the quantum yield of the AVA fluorescence was increased with the gradual addition of a surfactant at a concentration above its critical micellar level. This knowledge has been exploited to enhance the effectiveness of a spectrofluorometric technique for the estimation of AVA in human plasma (98.95 ± 1.22%) and uniformity tests with greenness assessments. The conditions for enhanced fluorescence were optimized and fully validated using US-FDA and International Conference on Harmonization (ICH) rules. This innovative strategy was expanded for AVA stability research in human plasma across various circumstances. This approach is an eco-friendly solution compared to traditional testing methods that use hazardous chemicals.

Regulatory Authority in Pharmacovigilance

Abstract: Based on their Gross National Income (GNI) per capita, the World Bank has categorized 80 economies as HighIncome. Global pharmacovigilance rules are primarily driven by three major regulatory stakeholders: the Food and Drug Administration (FDA), the European Medicines Agency (EMA), and the Pharmaceuticals and Medical Devices Agency (PMDA). This article's goal is to provide an overview of pharmacovigilance systems and procedures in high-income nations, especially those that are also International Conference on Harmonization (ICH) members. Every high-income nation is a part of the WHO PIDM. Medication safety precautions are directly correlated with a nation's income level. The 10 intrepid members of the Uppsala Monitoring Center are from affluent nations and were among the first to act following the thalidomide catastrophe, establishing drug appraisal committees, launching ADR reporting forms, and implementing safety protocols. Although VigiBase is accessible, several nations have their own databases for data management and analysis, such as the FDA Adverse Event Reporting System, the French pharmacovigilance database, the EU's Eudravigilance system, and Canada's Vigilance online database. Strong pharmacovigilance systems are present in all high-income nations. The two international leaders in pharmacovigilance are the USFDA and EMA. The majority of wealthy nations adhere to EMA regulations. The degree of affluence in a nation directly affects the safety of medicines.

Simultaneous UV Spectrophotometric Method for Estimation of Berberine and Withanolide in Polyherbal Immunity Booster Dosage Form

The majority of commercial herbal preparations used to improve immunity lack standardization with regard to the active ingredients marker molecules. The objective of present study is the simultaneous estimation of berberine and withanolide in herbal immunity booster tablet using UV spectrophotometric method. The method was validated according to ICH guidelines. The results indicated that berberine and withanolide have maximal absorption wavelength i.e. λmax at 348 nm and 231 nm, respectively. Withanolide and berberine were found to behave linearly over the concentration range of 5–25μg/mL with R2 value of 0.9998 and 0.9999, respectively. Withanolide and berberine have shown % relative standard deviation (RSD) values of 0.07 and 0.09, respectively, in accuracy study. The intraday and interday precision was deemed adequate with a % RSD fewer than 2. Further, the limit of detection (LOD) and limit of quantization (LOQ) value for berberine and withanolide were found to be 0.12 mg/mL and 0.35mg/mL and 0.07, 0.20 mg/mL, respectively. In conclusion, the proposed method was validated in accordance with the International Conference on Harmonization (ICH) guidelines. The developed method can be employed to determine how much berberine and withanolide are present in pharmaceutical preparations.

BAZI TIBBİ BİTKİLERDE ATOMOKSETİN TAYİNİ İÇİN YENİ BİR UHPLC-DAD YÖNTEMİNİN GELİŞTİRİLMESİ VE VALİDASYONU

Objective: Atomoxetine (ATX) is a medication that is extensively used to treat attention deficit hyperactivity disorder in children, adolescents, and adults. The goal of this work was to create a speedy, easy, and sensitive ultra high performance liquid chromatographic method (UHPLC) for the measurement of atomoxetine in various medicinal plants. (Salvia officinalis L., Rosmarinus officinalis L., Melissa officinalis L., Ginkgo biloba L.). Material and Method: Prior to chromatographic separation, liquid-liquid extraction was applied, which is currently the preferred extraction technique due to its simple, fast and efficient procedure for sample preparation. The chromatographic separation was achieved by reversed phase C18 (5 μm × 4.6 mm × 150 mm) analytical column and a mobile phase consisting of monobasic potassium dihydrogen orthophosphate (pH=6.8) and acetonitrile (50:50 v/v) at flow rate of 0.8 ml/min and diode array detector (DAD) detecting at 215±2 nm. Result and Discussion: The envisioned method's linear behavior was tested in the 0.5-20 μg/ml range (r2=0.09990). In compliance with International Conference on Harmonisation (ICH) criteria, the method received validation by means of accuracy, precision, repeatability, specificity, robustness, and detection and quantification boundaries. LOD and LOQ values were determined as 0.16 and 0.5 μg/ml. RSD values for hourly and daily measurements are found to be below 2.5% for both assays. The proposed method can be used effectively for quantification of atomoxetine in medicinal and aromatic plants. The proposed analytical procedure represents an efficient method for the quantification and routinee analysis of atomoxetine in medicinal and aromatic plants.

AZƏRBAYCANDA YAYILAN ADİ MAYASARMAŞIĞI (HUMULUS LUPULUS L.) BİTKİSİNDƏN ALINAN EKSTRAKTDA FİTOESTROGENLƏRİN MİQDARİ ANALİZ ÜSULUNUN İŞLƏNİB HAZIRLANMASI VƏ VALİDASİYASI

The aim of the study is to develop and validate a method for spectrophotometric determination of phytoestrogens in the phytoextract obtained from cones of hop (Humulus lupulus L.), which is widespread in Azerbaijan. The extract and standard (ethinyl estradiol) obtained from the cones of hop were used in the research. Evaluation of the validation of the method of quantitative determination of phytoestrogens in the extract by spectrophotometry was carried out on the parameters of accuracy, precision and linearity. Determining the accuracy of the obtained results determines whether the method meets the current requirements. Determination of determination and quantification limits was performed based on the standard deviation of the y-intercept and intercept coefficient parameters according to the guidelines of the International Conference on Harmonization (ICH). The limits of determination and quantification were determined to be 0.012 mg/ml and 0.035 mg/ml, respectively. This is in modern medicinal forms (phytomicrosphere, microsphere, phytosome) prepared by us from hop cones and existing preparations ("Fitoestrin", "Klimarin", "Lifemin", "Femesse", "Ligunin", "Fitomix", "Fitovit", etc.). ) will create a basis for determining the amount of phytoestrogens.