Quality Control Laboratories Research Articles

Concepts for a New Rapid and Simple HPLC Method for Simultaneous Determination of Rosuvastatin and Perindopril in Dosage Forms

ABSTRACTSimultaneous determination of a tandem of drugs like perindopril and rosuvastatin with differences in water and organic solvent solubilities, hydrophobicity, polarities, and UV‐absorbing possibilities between them necessitates careful selection of chromatographic conditions. The four specified and different bonded reversed‐phase columns were tested with running mobile phases containing various composition contents concepts; the concept of using diluted trifluoroacetic acid in mobile phase composition with acetonitrile enabled simultaneous acidification and weak ion‐pairing with protonized molecules of analytes, yielding appropriate, short, reasonable run times and resolutions of analytes, satisfying UV‐transparency, and good peak symmetries. These facts especially stand for the peak of perindopril, as a member of the group of proline‐containing moiety in its structure, often and easily prone to peak‐tailing, skewing, or splitting on the high‐performance liquid chromatography chromatograms, which is usually solved by using alkyl‐sulfonate base and ion pairs on higher concentrations of buffering salts with low pH values and with column temperatures increasing by 50°C–60°C. Linearity range was 0.002/004–0.5 mg/mL. The score for method AGREE was 0.73–0.77. The method development approaches, with all columns employing our concepts in mobile phases and experimental conditions, can cover the complete needs and demands of quality control departments and laboratories as simple high‐throughput analysis methods.

IDENTIFICATION OF PARASITES INFECTING TILAPIA (Oreochromis niloticus) IN CULTURE PONDS IN KUANHEUM VILLAGE

Parasites are one of the main problems faced by fish farmers in Kupang district. The study aimed to identify parasites infecting tilapia (O. niloticus) in culture ponds in Kuanheum Village, Kupang Regency, East Nusa Tenggara. Tilapia (O. niloticus) were taken randomly and parasite identification observations were made at the Kupang Fish Quarantine, Quality Control and Fishery Product Safety Station Laboratory. The results were analyzed descriptively. The results of parasite identification showed that two types of parasites were found in tilapia (O. niloticus) in Kuanheum Village, namely Trichodina sp. and Cichlidogyrus sp.

Point-of-care testing: state-of-the art and perspectives.

Point-of-care testing (POCT) is becoming an increasingly popular way to perform laboratory tests closer to the patient. This option has several recognized advantages, such as accessibility, portability, speed, convenience, ease of use, ever-growing test panels, lower cumulative healthcare costs when used within appropriate clinical pathways, better patient empowerment and engagement, and reduction of certain pre-analytical errors, especially those related to specimen transportation. On the other hand, POCT also poses some limitations and risks, namely the risk of lower accuracy and reliability compared to traditional laboratory tests, quality control and connectivity issues, high dependence on operators (with varying levels of expertise or training), challenges related to patient data management, higher costs per individual test, regulatory and compliance issues such as the need for appropriate validation prior to clinical use (especially for rapid diagnostic tests; RDTs), as well as additional preanalytical sources of error that may remain undetected in this type of testing, which is usually based on whole blood samples (i.e.,presence of interfering substances, clotting, hemolysis, etc.). There is no doubt that POCT is a breakthrough innovation in laboratory medicine, but the discussion on its appropriate use requires further debate and initiatives. This collective opinion paper, composed of abstracts of the lectures presented at the two-day expert meeting "Point-Of-Care-Testing: State of the Art and Perspective" (Venice, April 4-5, 2024), aims to provide a thoughtful overview of the state-of-the-art in POCT, its current applications, advantages and potential limitations, as well as some interesting reflections on the future perspectives of this particular field of laboratory medicine.

Comparative study on the quality control effectiveness of AI-PBRTQC and traditional PBRTQC model in identifying quality risks.

We compared the quality control efficiency of artificial intelligence-patient-based real-time quality control (AI-PBRTQC) and traditional PBRTQC in laboratories to create favorable conditions for the broader application of PBRTQC in clinical laboratories. In the present study, the data of patients with total thyroxine (TT4), anti-Müllerian hormone (AMH), alanine aminotransferase (ALT), total cholesterol (TC), urea, and albumin (ALB) over five months were categorized into two groups: AI-PBRTQC group and traditional PBRTQC group. The Box-Cox transformation method estimated truncation ranges in the conventional PBRTQC group. In contrast, in the AI-PBRTQC group, the PBRTQC software platform intelligently selected the truncation ranges. We developed various validation models by incorporating different weighting factors, denoted as λ. Error detection, false positive rate, false negative rate, average number of the patient sample until error detection, and area under the curve were employed to evaluate the optimal PBRTQC model in this study. This study provides evidence of the effectiveness of AI-PBRTQC in identifying quality risks by analyzing quality risk cases. The optimal parameter setting scheme for PBRTQC is TT4 (78-186), λ = 0.03; AMH (0.02-2.96), λ = 0.02; ALT (10-25), λ = 0.02; TC (2.84-5.87), λ = 0.02; urea (3.5-6.6), λ = 0.02; ALB (43-52), λ = 0.05. The AI-PBRTQC group was more efficient in identifying quality risks than the conventional PBRTQC. AI-PBRTQC can also effectively identify quality risks in a small number of samples. AI-PBRTQC can be used to determine quality risks in both biochemistry and immunology analytes. AI-PBRTQC identifies quality risks such as reagent calibration, onboard time, and brand changes.

Quantification of heavy metals in wild gravid female mud crab (Scylla olivacea) collected from different rivers of Sundarbans mangrove region

Heavy metals pollution is one of our major problems in Sundarbans mangrove zone as we all their surrounding rivers. The presence of industrial development in the nearby areas of coastal and marine aquacultures sites are the cause of heavy metals pollution. The aim of the research was to quantify heavy metals in gravid female mud crabs (Scylla olivacea) in three different rivers of Sundarbans region. Mud crabs and their surrounding water and soil sediments were collected from Mongla, Kholpetua, and Kopotakkho rivers. Analysis of river water was conducted in the laboratory of Shiva Analyticals (India) Private Limited, India, whereas live mud crabs and sediment samples were analyzed from Quality Control Laboratory (QCL), Khulna, Bangladesh for the quantification of heavy metals. The results showed that the heavy metals As, Cr, Cd, Hg and Pb were detected in mud crabs and their surrounding river water and sediments, but the concentration of heavy metals in mud crabs was remains below the limit of human’s consumptions except the heavy metal Chromium (Cr). Maximum concentration of heavy metals was detected Kopotakkho river followed by Mongla and Kholpetua river. The concentration of heavy metals was highest in soil sediments followed by mud crabs and river waters. Mud crabs were contaminated by heavy metals that bioaccumulated from their surrounding sediments and water sources. The hierarchy of mean concentrations (mg/kg) of the heavy metals were Pb>As>Cr>Pb>Hg. Heavy metals are carcinogenic for human consumption when exceeded their permissible levels. It is urgent to stop pollution in Sundarbans mangrove zone and led to serve healthy foods for the nations.

Challenging the gold standard: the limitations of molecular assays for detection of Mycobacterium tuberculosis heteroresistance

ObjectivesHeteroresistant infections are defined as infections in which a mixture of drug-resistant and drug-susceptible populations are present. In Mycobacterium tuberculosis (M. tb), heteroresistance poses a challenge in diagnosis and has...

Analysis and authentication of avocado oil by low-field benchtop NMR spectroscopy and chemometrics.

Avocado oil is a nutritious, edible oil produced from avocado fruit. It has high commercial value and is increasing in popularity, thus powerful analytical methods are needed to ensure its quality and authenticity. Recent advancements in low-field (LF) NMR spectroscopy allow for collection of high-quality data despite the use of low magnetic fields produced by non-superconductive magnets. Combined with chemometrics, LF NMR opens new opportunities in food analysis using targeted and untargeted approaches. Here, it was used to determine poly-, mono-, and saturated fatty acids in avocado oil. Although direct signal integration of LF NMR spectra was able to determine certain classes of fatty acids, it had several challenges arising from signal overlapping. Thus, we used partial least square regression and developed models with good prediction performance for fatty acid composition, with residual prediction deviation ranging 3.46-5.53 and root mean squared error of prediction CV ranging 0.46-2.48. In addition, LF NMR, combined with unsupervised and supervised methods, enabled the differentiation of avocado oil from other oils, namely, olive oil, soybean oil, canola oil, high oleic (OL) safflower oil, and high OL sunflower oil. This study showed that LF NMR can be used as an efficient alternative for the compositional analysis and authentication of avocado oil. PRACTICAL APPLICATION: Here, we describe the application of LF-NMR for fatty acid analysis and avocado oil authentication. LF-NMR can be an efficient tool for targeted and untargeted analysis, thus becoming an attractive option for companies, regulatory agencies, and quality control laboratories. This tool is especially important for organizations and entities seeking economic, user-friendly, and sustainable analysis solutions.

Methodological Validation of Sedimentation Velocity Analytical Ultracentrifugation Method for Adeno-Associated Virus and Collaborative Calibration of System Suitability Substance.

Currently, adeno-associated virus (AAV) is one of the primary gene delivery vectors in gene therapy, facilitating long-term invivo gene expression. Despite being imperative, it is incredibly challenging to precisely assess AAV particle distribution according to the sedimentation coefficient and identify impurities related to capsid structures. This study performed the systematic methodological validation of quantifying the AAV empty and full capsid ratio. This includes specificity, accuracy, precision, linearity, and parameter variables involving the sedimentation velocity analytical ultracentrifugation (SV-AUC) method. Specifically, SV-AUC differentiated among the empty, partial, full, and high sedimentation coefficient substance (HSCS) AAV particles while evaluating their sedimentation heterogeneity. The intermediate precision analysis of HE (high percentage of empty capsid) and HF (high percentage of full capsid) samples revealed that the specific species percentage, such as empty or full, was more significant than 50%. Moreover, the relative standard deviation (RSD) could be within 5%. Even for empty or partially less than 15%, the RSD could be within 10%. The accuracy recovery rates of empty capsid were between 103.9% and 108.7% across three different mixtures. When the measured percentage of specific species was more significant than 14%, the recovery rate was between 77.9% and 106.6%. Linearity analysis revealed an excellent linear correlation between the empty, partial, and full in the HE samples. The AAV samples with as low as 7.4 × 1011 cp/mL AAV could be accurately quantified with SV-AUC. The parameter variable analyses revealed that variations in cell alignment significantly affected the overall results. Still, the detection wavelength of 235 nm slightly influenced the empty, partial, and full percentages. Minor detection wavelength changes showed no impact on the sedimentation coefficient of these species. However, the temperature affected the measured sedimentation coefficient. These results validated the SV-AUC method to quantify AAV. This study provides solutions to AAV empty and full capsid ratio quantification challenges and the subsequent basis for calibrating the AAV empty capsid system suitability substance. Because of the AAV structure and potential variability complexity in detection, we jointly calibrated empty capsid system suitability substance with three laboratories to accurately detect the quantitative AAV empty and full capsid ratio. The empty capsid system suitability substance could be used as an external reference to measure the performance of the instrument. The results could be compared with multiple QC (quality control) laboratories based on the AAV vector and calibration accuracy. This is crucial for AUC to be used for QC release and promote gene therapy research worldwide.

Verification of the analytical performance of the serum magnesium assay on Abbott Architect ci8200

Magnesium is recognized as the fourth most important cation in the body and the second most abundant intracellular cation, following potassium. Its physiological significance lies in its capacity to form complexes with crucial intracellular anionic ligands, notably ATP, and its ability to compete with calcium for specific binding sites on proteins and cell membranes. Over 300 enzyme reactions rely on magnesium. The concentration of free magnesium within cells determines the magnesium content of these enzymes. Magnesium influences myocardial contraction and the electrical activity of myocardial cells, as well as the specialized conduction systems of the fetus, by modulating the transmembrane movements of ions like sodium, potassium, and calcium. Furthermore, magnesium can affect the contractility of vascular smooth muscle, and alterations in intracellular magnesium levels may impact cell proliferation or contraction. Magnesium is involved in nucleic acid and protein metabolism, intermediary metabolism, energy production, and consumption reactions, and it plays specific roles in various physiological systems such as the neuromuscular and cardiovascular systems. Our research aims to assess the analytical accuracy of the serum magnesium assay method utilizing an Abbott kit on the Architect ci8200 automated system in the biochemistry laboratory of Mohammed VI University Hospital of Oujda. The evaluation of the kit's analytical accuracy was conducted within the flexible scope A by conducting a performance analysis on the Architect ci8200. We examined repeatability, reproducibility, measurement imprecision, and compared results between two Architect ci8200 instruments. All findings align with the acceptability criteria recommended by the supplier and the Valtec protocol of the Société Française de Biologie Clinique (SFBC), indicating overall satisfactory outcomes for the study. The Architect ci8200 automated system demonstrated satisfactory analytical performance for reliably determining serum magnesium levels. Method verification in medical laboratories is essential to guarantee the accuracy, precision, and reliability of test results. Verification entails confirming that the test method used is suitable for its intended purpose, yields result consistent with the claimed performance characteristics, and meets the laboratory's quality control and quality assurance standards.

The diagnostic accuracy of quality control rules

Internal quality control in clinical chemistry laboratories are based on analyzing samples of stable control materials among the patient samples. The control results are interpreted by using quality control rules that usually are designed to detect systematic errors. The best rules have a high probability of error detection (Ped), i.e. to detect the maximal allowable (critical) systematic error and a low probability of false rejection (Pfr, false alarm). In this work we show that quality control rules can be represented by points on a ROC curve which appears when Ped is plotted against Pfr and only the control limit is varied. Further, we introduce a new method for choosing the optimal control limit, analogous to choosing the optimal operating point on the ROC curve of a diagnostic test. This decision needs knowledge of the pretest probability of a critical systematic error, the benefit of detecting it when it occurs and the cost of false alarm. The ROC curve analysis showed that if rules based on N = 2 are used, mean rules outperform Westgard rules because the ROC curve of the mean rules was lying above the ROC curves of the Westgard rules. A mean rule also had a lower maximum expected increase in the number of unacceptable patient results reported during the presence of an out-of-control error condition (Max E(NUF)) than comparable Westgard rules.

Oral tobacco-free nicotine products: Quality and safety during storage

Oral non-tobacco nicotine products have gained enormous popularity in recent years. The countries of the Eurasian Economic Union also produce and sell this type of innovative but poorly studied goods. As a result, the safety profile and quality of such products as nicotine poaches require urgent comprehensive research. This study featured the changes in quality of nicotine poaches during storage, i.e. nicotine content, water activity, and microbiological index. The research featured nicotine poaches of several popular brands. The authors used standard research methods; the experiments were performed in the laboratory for chemistry and quality control, Institute of Tobacco, Makhorka, and Tobacco Products, Krasnodar, and at the Department of Bioorganic Chemistry and Technical Microbiology, Kuban State Technological University, Krasnodar. The water activity was 0.8911–0.9502 Aw at the initial stage and remained stable in most samples even after six months of storage. Velo Freeze was the only brand to show significant variations in water activity. The nicotine content was 10.115–12.950 mg/g at the initial stage. Only four samples maintained the initial values after six months of storage. The fluctuations of nicotine content were also mentioned by the manufacturer. The microbiological profile remained stable during the six months of storage and met the requirements for similar products, i.e., chewing gum and unglazed caramel. The project needs further research because the qualitative characteristics of nicotine poaches provided rather unambiguous results. Our study will help develop state standards for oral nicotine products. The results obtained will be used to formulate proposals to the organizations responsible for the future Technical Regulations of the Eurasian Economic Union for nicotine products.

Development and validation of stability indicating ultra‐high‐performance liquid chromatographic method for assay and impurities of mexiletine hydrochloride and mexiletine hydrochloride capsules

AbstractMexiletine (MEX) is an antiarrhythmic drug used to treat acute and chronic ventricular arrhythmias. A simple isocratic, rapid, specific, stability‐indicating, and sensitive reverse‐phase ultra‐high‐performance liquid chromatography (UHPLC) method was developed and successfully validated to quantify the assay and impurities of MEX hydrochloride. The new UHPLC method showed the optimum separation of MEX and its seven impurities in 20 min by using sodium acetate buffer (0.14 mM) with 0.3% of glacial acetic acid (pH 4.8) and methanol in the ratio of 40:60 (v/v) as mobile phase. The method used an Acquity HSS T3 (100 × 3.0 mm, 1.8 µm) chromatographic column at a 0.2 mL/min flow rate. The injection volume is 2 µL, and 254 nm is the detection wavelength. Note that, 25°C is the column oven temperature. The method is linear over the concentration range of the quantification limit (0.03%) to 150% (0.3%) of the specification level (0.2%) for the impurities and 50%–150% for the assay method. The quality control lab of bulk drugs and finished dosage form successfully applied the new UHPLC method for quantification of assay and impurities of MEX hydrochloride.

Quantitative determination of lobeglitazone sulfate and glimepiride in combined tablet by robust high‐performance thin layer chromatographic method

AbstractA combination of fixed dose tablet containing 0.5 mg lobeglitazone sulfate (LBZ) and 1 mg glimepiride (GLM) has demonstrated efficacy in enhancing glycemic control in diabetes. The projected work aimed to develop and validate a high‐performance thin‐layer chromatographic (HPTLC) methodology for the precise quantification of both the drugs in tablet formulations. The HPTLC analysis utilized aluminium plates layered with silica gel 60F254, and the solvent system consisted of ethyl acetate, benzene, and hexane (4:3:1 v/v/v) followed by densitometric scanning at 238 nm. The Rf value was found to be 0.68 ± 0.001 for LBZ and 0.48 ± 0.002 for GLM. The methodology exhibited linearity in the range of 100–2000 ng/band for LBZ and 200–4000 ng/band for GLM, with correlation coefficients of 0.9988 and 0.9981, respectively. Exceptional sensitivity was observed, with detection limits of 23.86 ng/band for LBZ and 58.26 ng/band for GLM, along with quantification limits of 72.32 ng/band for LBZ and 176.55 ng/band for GLM. The method demonstrated precision (% relative standard deviation of peak area < 2) and accuracy (recovery between 97% and 102%). The suggested method is suitable for quantifying both the drugs in tablets, making it useful for routine quality control in laboratories.

Development and Evaluation of Chemometric Models for the Estimation of Sumatriptan in the Presence of Naproxen and a Degradation Product Using UV Spectrophotometry.

Chemometrics is a discipline that allows the spectral resolution of drugs in a pharmaceutical formulation along with degradation product and it is an alternative to chromatographic methods. Sumatriptan (SUM) is co-formulated with naproxen (NAP) and used in acute migraine attacks. SUM, which has physiological importance, has not been subjected to any stability-indicating chemometric approaches yet, so there is a need for an accurate and safe method for the assay of the cited drug in its preparations. The greenness and blueness assessment was applied using different ecological metrics, including the Green Analytical Procedure Index (GAPI), Analytical Greenness Metric (AGREE), Analytical Eco-Scale (AES) and new "blueness" evaluation using the Blue Applicability Grade Index (BAGI) tool. SUM was determined in pharmaceutical formulation along with NAP and in presence of alkali-induced degradation product with simple and cost-effective multivariate approaches using spectrophotometric data. Three chemometric approaches were applied for the stability-indicating determination of SUM in the presence of NAP. Classical least-squares (CLS), partial least-squaresregression (PLS), and principal components regression (PCR)-three multivariate calibration numerical models that were applied to the UV spectra of the mixtures-were used to achieve the best resolution. Sumatriptan was analyzed with mean accuracies for PLS (100.29% ± 1.318) and for PCR (100.60% ± 1.564). The presented methods were compared and validated for their quantitative analyses. Moreover, statistical comparison between the results obtained by the proposed models and the official methods showed no significant differences. The proposed multivariate calibrations were accurate and specific for quantitative analysis of the studied component. PLS is the best method that has the capacity for qualitative analysis of SUM and it is suitable for routine analysis and stability studies of SUM in QC laboratories. Various ecological assessment metrics confirmed the long-standing eco-friendliness of the suggested models. Severally overlapped mixtures of SUM along with co-formulated drug NAP and an alkali-induced degradation product were analyzed by three chemometric approaches. The analytical performance of PLS and PCR was compared and validated in terms of root-mean-square error of calibration (RMSEC), SE of prediction, and recoveries. PLS gave the highest predicted concentrations with the lowest RMSEC and root-mean-square error of prediction. The standard addition was applied for accuracy assessment and the results were compared to those of official methods. Proposed models determined SUM in synthetic mixtures and pharmaceutical formulation in QC laboratories and stability studies. Ecological evaluation tools for measuring the environmental friendliness of chemicals were utilized for the first time in the analysis of SUM.

Quality assessment of oral antimalarial and antiretroviral medicines used by public health systems in Sahel countries

Malaria and Human Immunodeficiency Virus infections are among the top 10 causes of death in low income countries. Furthermore, many medicines used in these treatment areas are substandard, which contributes to the high death rate. Using a monitoring system to identify substandard and falsified medicines, the study aims to evaluate the quality of antimalarial and antiretroviral medicines in Sahel countries, assessing site conditions, compliance of medicines with pharmacopoeia tests, formulation equivalence with a reference medicine, and the influence of climate on quality attributes. Ultra Performance Liquid Chromatography methods for eight active pharmaceutical ingredients were validated following the International Conference for Harmonization guideline for its detection and quantification. Quality control consists of visual inspections to detect any misinformation or imperfections and pharmacopeial testing to determine the quality of pharmaceutical products. Medicines which complied with uniformity dosage units and dissolution tests were stored under accelerated conditions for 6 months. Artemether/Lumefantrine and Lopinavir/Ritonavir formulations failed uniformity dosage units and disintegration tests respectively, detecting a total of 28.6% substandard medicines. After 6 months stored under accelerated conditions (40 °C // 75% relative humidity) simulating climatic conditions in Sahel countries, some medicines failed pharmacopeia tests. It demonstrated the influence of these two factors in their quality attributes. This study emphasizes the need of certified quality control laboratories as well as the need for regulatory systems to maintain standards in pharmaceutical manufacturing and distribution in these countries, especially when medicines are transported to rural areas where these climatic conditions are harsher.

QUANTITATIVE DETERMINATION OF SOME NON-STEROIDAL ANTI-INFLAMMATORY DRUGSAND THEIR ACID DISSOCIATION CONSTANTS BY DIRECT POTENTIOMETRY

Objective: A potentiometric titration method was applied to determine non-steroidal anti-inflammatory drugs. The quantitative analysis and the treatment of the primary data are based on a nonlinear regression procedure using commercial software. A general formula valid for every type of acid-base titration, derived before is used as a direct input. Methods: Potentiometric titration of ibuprofen, flurbiprofen, and ketoprofen with sodium hydroxide solution (0.1 mol/l). The solutions of ibuprofen, flurbiprofen, and ketoprofen were prepared in solvent CH3OH: H2O (40:60%). The determination was carried out using a 713 Metrohm pH meter, equipped with Metrohm combined electrode ref. 6.0228.000 Pt1000 with temperature sensor and auto burette. The analysis was performed at ionic strength (I=0.2 mol/l KCl) and t = 25±0.2 °C. Results: The discussed substances were analyzed using potentiometric titration with a standard sodium hydroxide solution (0.1 mol/l). The experimental data V, ml/E, mV and the conditions of these titrations were used as input in the Data Fit program fixing the following parameters Vo =100.0 ml; Ct (NaOH) = 0.1000 mol/l; S = 59.16 mV (corresponding to 25 °C theoretical value) and Kw = 1.2 10-14 (ionic strength 0.2 mol/l). The analytical results for ibuprofen, flurbiprofen and ketoprofen were determined with good accuracy (error+0.4 % foribuprofen+0.2 % for flurbiprofen and+0.2 % for ketoprofen) and precision (1 % for the three). The quantity and acid-base constants of ibuprofen, flurbiprofen, and ketoprofen were determined alone and in tablets. The validation of the method showed very good accuracy and precision. Conclusion: The present approach can be successfully used in routine analysis of the study drugs in quality control laboratories.

QUANTIFICATION AND QUALITY CONTROL OF TRIPLE-DRUG COMBINATION EMPLOYED FOR GASTRIC ULCER USING STABILITY-INDICATING SELECTIVE RP-HPLC TECHNIQUE

Objective: A seven-day regimen consisting of vonoprazan (VNP), amoxicillin (AXC) and clarithromycin (CRC), administered twice daily, has been permitted and reimbursed by health coverage as initial therapy. No technique has been implemented yet to determine the quantities of VNP, AXC, and CRC combination. This work effectively aimed at estimating these medications (VNP, AXC, and CRC) at the same time by developing an HPLC technique that saves money and time. Methods: The VNP, AXC, and CRC were separated in a “Waters” column (C18 nature; 250 mm sized length; 4.6 mm sized internal diameter; 5 µm sized particle; 25 °C temperature). Phosphoric acid (0.1% in water; pH 4.2) and absolute methanol (50:50, v/v) comprise the mobile phase. The drug product, Voqueznatripak, was subjected to hydrolysis, oxidation, photolysis, and thermal stressors with the intent to cause enforced degradation. The suggested "HPLC conditions" were verified in compliance with ICH guidance. Results: The measurements had a linear range of 10–20 µg/ml for VNP and 250–750 µg/ml for AXC and CRC. The AXC, CRC, and VNP had LOQ’s 5.302 µg/ml, 5.487 µg/ml and 0.523 µg/ml, respectively. Precision measurements were<0.2% RSD and accuracy ranges were 99.40% to 101.46%. The newly devised “HPLC conditions” specificity attribute and stability-indicating quality were also validated by forced degradation tests. Conclusion: The newly devised “HPLC conditions” for analysing AXC, CRC, and VNP in formulation dosage form and stability samples might be adapted by quality control laboratories. The devised “HPLC conditions” is qualified and consistent to reveal and detect any probable change in the drug product assessments throughout stability experiments.

SARS-CoV-2 spike protein expression as an identification in quality control testing for Adenovector based COVID-19 vaccine

AimQuality control testing of the vaccine for lot release is of paramount importance in public health. A recent pandemic caused by the SARS-CoV-2 virus brought together all spheres of vaccine to combat the virus. The scientific advancement in the development of vaccines facilitated the scientists to develop the vaccine against SARS-CoV-2 in a record time. Thus, these vaccines should be stringently monitored for their safety and efficacy as per the latest WHO and national regulatory guidelines, and quality control evaluation of the product should be done at national control laboratories before releasing the product into the market as it assures the quality and safety of the vaccine. MethodsThe SARS-CoV-2 exploited the ACE2 (Angiotensin Converting Enzyme 2) receptor, a surface protein on mammalian cells to gain entry into the host cells. The viral surface protein that interacted with the ACE2 receptor is the Spike protein of SARS-CoV-2. Thus, in the development of the vaccine and assessing its quality, the Spike protein of SARS-CoV-2 became an attractive immunodominant antigen. In National Institute of Biologicals, an apex body in the testing of biologicals in India, received the Adenovector (Adenovirus + vector) based COVID-19 vaccine, a finished product for quality evaluation. Due to the lack of a pharmacopeial monograph, the testing of the vaccine was done as per the manufacturer's specifications and methods. The routine assays of identification employed by the manufacturer do not reflect the expression of Spike protein which is required for the immune system to get activated. In this report, we showed the determination of Spike protein expression by immunoblotting and immunofluorescence for identification parameters in the quality testing of the COVID-19 vaccine. We determined the translation of the SARS-CoV-2 Spike gene cloned into an Adenovector. ResultsThe results from these experiments indicated the expression of Spike protein upon infection of mammalian cells with viral particles suggested that the expression of immunodominant Spike protein of SARS-CoV-2 may be employed by quality control laboratories as a parameter for identification. ConclusionThe study suggested that the determination of the expression of Spike protein is pertinent to identifying the Adenovector based vaccines against COVID-19.

Development and validation of a sensitive and robust chiral method for (R)-propylene oxide: From chiral gas chromatography to chiral liquid chromatography with pre-column derivatization

Propylene oxide (PO) is an important chemical commodity and a chiral building block to prepare pharmaceutical compounds. It is crucial to develop a sensitive and robust chiral method that can be used to assess the enantiomeric purity of PO and safeguard the quality and safety of pharmaceutical products in commercial quality control (QC) laboratories. A chiral gas chromatography (GC) method based on direct enantioseparation of PO enantiomers on a 50-meter Chiraldex™ A-TA open capillary column was successfully developed for determination of enantiomeric impurity (S)-PO in (R)-PO. However, it was revealed that the chiral GC method lacked adequate robustness for routine use. Consequently, a chiral high-performance liquid chromatography (HPLC) method was developed through pre-column derivatization of PO with 2-naphthalenethiol followed by enantioseparation on a Lux Cellulose-1 (250 mm × 4.6 mm, 5 µm) column. The chiral HPLC method has been demonstrated excellent specificity, sensitivity, accuracy and robustness through method validation and robustness evaluation, thus establishing its suitability for routine use in QC laboratories.

Internal audit of quality control in the hormonology laboratory of Pierre and Marie Curie Center, Algiers

Internal audit of quality control in the hormonology laboratory of Pierre and Marie Curie Center, Algiers