Routine Quality Control Testing Research Articles

Innovative Reversed-Phase Chromatography Platform Approach for the Fast and Accurate Characterization of Membrane Vesicles' Protein Patterns.

Outer membrane vesicles (OMVs) have been widely explored to develop vaccine candidates for bacterial pathogens due to their ability to combine adjuvant properties with immunogenic activity. OMV expresses a variety of proteins and carbohydrate antigens on their surfaces. For this reason, there is an analytical need to thoroughly characterize the species expressed at their surface: we here present a simple and accurate reversed-phase ultrahigh-performance liquid chromatography (RP-UPLC) method developed according to quality by design principles. This work provides an analytical alternative to the classical sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) characterization. The higher selectivity and sensitivity of the RP-UHPLC assay allow for the identification of additional protein species with respect to SDS-PAGE and facilitate its precise relative abundance quantification. According to validation results, the assay showed high accuracy, linearity, precision, repeatability, and a limit of quantification of 1% for less abundant proteins. This performance paves the way for improved production campaign consistency while also being analytically simple (no sample pretreatment required), making it suitable for routine quality control testing. In addition, the applicability of the assay to a wider range of vesicle classes (GMMA) was demonstrated.

Trace level quantification of N-nitrosorasagiline in rasagiline tablets by LC-TQ-MS/MS

Parkinson's disease is a chronic, progressive neurological disease that currently affects about more than 10 million population worldwide. Rasagiline is a selective, irreversible monoamine oxidase type B inhibitor used as monotherapy in early Parkinson's disease. Rasagiline tablets have been recalled from market due to the presence of unacceptable levels of nitrosamine impurity. European Medical Agency has set up very stringent limit 100ng/day of N-nitrosorasagiline (NSRG) in drug product based on its mutagenicity. The analytical methods need to be sufficiently sensitive in order to adequately detect and quantify trace levels of NSRG. A highly sensitive LC-MS/MS method for determination of NSRG in rasagiline tablet formulation was developed by effectively separating on zorbax eclipse XDB C18 column using 0.1% formic acid in mixture of water and acetonitrile (35:65 v/v) in an isocratic mode at 0.5mL/min flow rate. The measurement of NSRG was performed using triple quadrupole mass detection accompanied by electrospray ionization in the multiple reaction monitoring mode. The validation of the method was comprehensive, demonstrating strong linearity across the concentration spectrum of 2 to 200ng/mL for NSRG. The obtained correlation coefficient exceeded 0.998, signifying a robust relationship. Recoveries spanning from 80.0% to 120.0% for NSRG were deemed satisfactory. The developed method was able to detect and quantitate NSRG at a concentration level of 1 to 2ng/mL respectively (1 to 2ppm with respect to 1mg/mL of rasagiline tablet sample concentration). The developed and validated method can be employed for routine quality control testing of rasagiline tablets.

Channelized hotelling observer-based low-contrast detectability on the ACR CT accreditation phantom: Part II. Repeatability study.

Objective and quantitative evaluation for low-contrast detectability that correlates with human observer performance is lacking for routine CT quality control testing. Channelized Hotelling observer (CHO) is considered a strong candidate to fill the need but has long been deemed impractical to implement due to its requirement of a large number of repeated scans in order to provide accurate and precise estimates of index of detectability (d'). In our previous work, we optimized a CHO model observer on the American College of Radiology (ACR) CT accreditation phantom and achieved accurate measurement of d' with only 1-3 repeat scans. In this work, we aim to validate the repeatability of the proposed CHO-based low-contrast evaluation on four scanner models using the ACR CT accreditation phantom. The repeatability test was performed on four different scanners from two major CT manufacturers: Siemens Force and Alpha; Canon Prism and Prime SP. An ACR CT phantom was scanned 10 times, each time after repositioning of the phantom. For each repositioning, 3 repeated scans were acquired at 24, 12, and 6 mGy on all four scanner models. CHO was applied at the measured dose levels for different low-contrast object sizes (4-6mm). The CHO was also applied to images created using deep learning-based reconstructions on Canon Prism and to four different scan/reconstruction modes on the Siemens Alpha, a photon-counting-detector (PCD)-CT. The repeatability was evaluated by the probability that a measurement would fall within the±15% tolerance (P<15% ). With the CHO setting optimized for the ACR phantom and the use of 3 repeated scans and 9 non-overlapping slices per scan, the CHO measurement could provide high repeatability with P<15% of 98.8%-99.9% at 12 mGy with IR reconstruction on all four scanners. On scanner A, P<15% were 91.5%-99.9% at the three dose levels and for all three object sizes while the numbers were 93.6%-99.998% on scanner B. P<15% were 96.5%-97.2% for the two deep learning reconstructions and 97.0%-99.97% for the four scan/reconstruction modes on the PCD-CT. The CHO provided highly repeatable measurements with over 95% probability that a CHO measurement would lie within the±15% tolerance for most of the dose levels and object sizes on the ACR phantom. The repeatability was maintained when the CHO was applied to images created with a commercial deep learning-based reconstruction and various scan/reconstruction modes on a PCD-CT. This study demonstrates that practical implementation of CHO for routine quality control and performance evaluation is feasible.

A novel stability indicating mass compatible reversed‐phase high‐performance liquid chromatography for the determination of Diroximel fumarate and its related impurities

AbstractDiroximel fumarate (DRF) is a novel oral fumarate used in the treatment of multiple sclerosis. Comprehending DRF's stability behavior in different degradation conditions is crucial and has been studied under photolysis, oxidative, hydrolysis, and thermal conditions. Nucleosil C18 column (250 × 4.6 mm, 5 μm) was employed to achieve drug separation, with a mobile phase comprising of water and acetonitrile (65:35, v/v). The flow rate was 1 mL/min and detection was performed at 210 nm using a photodiode array detector. The fully validated reversed phase‐high‐performance liquid chromatography stability method as per the International Council for Harmonization Q2 R1 demonstrated excellent selectivity, accuracy, and precision with good sensitivity. During the analysis, two prominent degradant product peaks of DRF were identified across all stress conditions. The usage of liquid chromatography‐mass spectrometry compatible solvents in the mobile phase permits further characterization of DRF and its degradants peak. Significant levels of degradation were found in alkaline and acidic hydroxide, peroxide, photolytic, and thermal conditions with hydrolysis being postulated as a possible mechanism of degradation. The fully validated stability‐indicating analytical method can be used for routine quality control and stability testing of DRF, requiring storage in a protected primary container, as it is sensitive to light and moisture.

Development and Optimization of 11C-Labeled Radiotracers: A Review of the Modern Quality Control Design Process.

Introduction - Several 11C-tracers have demonstrated high potential in early diagnostic PET imaging applications of neurodegenerative diseases including Alzheimer's and Parkinson's disease. These radiotracers often track critical biomarkers in disease pathogenesis such as tau fibrils ([11C]PBB3) or β-amyloid plaques ([11C]PiB) associated with such diseases. Purpose - The short review aims to serve as a guideline in the future development of radiotracers for students, postdocs and/or new radiochemists who will be synthesizing clinical grade or novel research 11C-tracers, including knowledge of regulatory requirements. We aim to bridge the gap between novel and established 11C-tracer quality control (QC) processes through exploring the design process and regulatory requirements for 11C-pharmaceuticals. Methods - A literature survey was undertaken to identify articles with a detailed description of the QC methodology and characterization for each of the sections of the review. Overview - First a general summary of 11C-tracer production was presented; this was used to establish possible places for contamination or assurances for a sterile final product. The key mandated QC analyses for clinical use were then discussed. Further, we assessed the QC methods used for established 11C-tracers and then reviewed the routine QC tests for preclinical translational and validation studies. Therefore, both mandated QC methods for clinical and preclinical animal studies were reviewed. Last, some examples of optimization and automation were reviewed, and implications of the QC practices associated with such procedures were considered. Conclusion - All of the common QC parameters associated with 11C-tracers under clinical and preclinical settings (along with a few exceptions) were discussed in detail. While it is important to establish standard, peer-reviewed QC testing protocols for a novel 11C-tracer entering the clinical umbrella, equal importance is needed on preclinical applications to address credibility and repeatability for the study.

HYDROLYTIC DEGRADATION STUDY OF ROXADUSTAT BY RP-HPLC AND HPTLC

Objective: Simple, rapid RP-HPLC and HPTLC methods have been developed in order to study the degradation of Roxadustat under various stress conditions. The Kinetics of hydrolytic degradation is studied. Methods: Optimum separation of Roxadustat and its degradation products was achieved using the following conditions in HPLC, Agilent eclipse XDB-C8 (150×4.6 mm) column, the mobile phase was composed of methanol: phosphate buffer (pH 5, 0.05 M) (70:30 v/v) with UV detection at 262 nm. The flow rate was at 1.0 ml/min. The RT was 4.6±0.02 min. HPTLC work for Roxadustat was performed on Aluminium plates precoated with silica gel 60 F254, (10 cm × 10 cm with 250 μm layer thickness). The mobile phase was composed of Toulene: Ethyl Acetate: Glacial acetic acid (5:5:0.5 v/v/v) and then scanned. The system was found to give a compact spot for Roxadustat (Rf value of 0.58±0.02). Results: In HPLC the calibration curves plotted were found to be linear over the concentration range of 2.5-25μg/ml, with a correlation coefficient of R2=0.9994. In HPTLC the calibration curves plotted were found to be linear over the concentration range of 500-2500 ng/band, with a regression coefficient of R2=0.9957. The analytical performance of the proposed methods was validated as per ICH Q2 (R1) guidelines. The degradant peaks were well resolved from the Roxadustat peak. Significant degradation was observed in acid hydrolysis, alkali hydrolysis, and oxidative degradation. The drug is relatively stable towards photolysis, neutral hydrolysis, and thermal conditions. Conclusion: In the current work, simple RP-HPLC and HPTLC analytical methods for the determination of Roxadustat in the presence of its degradation products have been developed. The information presented herein could be very useful while developing formulation procedures to prevent hydrolytic degradation. It can be used as a routine quality control test.

Isolation, development and validation of HPTLC method for the estimation of β-carotene from Gymnosporia senegalensis (Lam.) Loes.

The present study is aimed to isolate terpenoids from Gymnosporia senegalensis through analytical and preparative thin-layer chromatography (TLC) and to determine their antioxidant activity using the 2, 2-diphenyl-1- picrylhydrazyl (DPPH) assay and to find out the presence of β-carotene through high-performance thin-layer chromatography (HPTLC). The validation included linearity, limit of detection (LOD), limit of quantification (LOQ), specificity, precision, recovery, and robustness. All the isolated compounds from TLC exhibited significant antioxidant activity. Among all, isolated compounds from leaf showed highest IC50 values. The highest total terpenoid content (TTC) was found 51.6 ± 0.06 in stem, then 49.02 ± 0.01 in bark, and 46.27 ± 0.01 in leaf. DPPH results indicated that leaf-isolated compound 1 (LIC1) showed the highest IC50 at 7.55 ± 0.02 and stem-isolated compound 2 (SIC2) showed the lowest IC50 at 0.616 ± 0.01 among all the isolated compounds of G. senegalensis. HPTLC separation was carried out on aluminium plates pre-coated with silica gel 60 F254 as the stationary phase and n-hexane: ethyl acetate (6:4, v/v) as the mobile phase. Quantification was achieved based on a densitometric analysis of β-carotene in the concentration range of 100–500 ng/band at 254 nm. For the calibration plots, linear regression produced r2 = 0.96450 and Rf = 0.27. The LOD and LOQ were 10.15 and 30.76 ng/mL for HPTLC and relative standard deviation were 137.26 ± 2.03 and 160.43 ± 2.95 (intra-day) and 127.88 ± 2.14 and 157.27 ± 1.90 (inter-day) for 200 and 400 ng/band, respectively. The present study shows the presence of various types of terpenoids through TLC whereas the HPTLC results indicated that the developed methods were accurate and precise. It also shows that the approach is appropriate for its intended use in routine quality control testing of commercially available tablet formulations and drug assay to assist both industries and researchers in making important decisions at a reasonable cost. Moreover, due to the use of a safer and more environmentally friendly mobile phase in comparison to the toxic mobile phases used in recent analytical techniques to estimate β-carotene, this methodology is also secure and sustainable.

Sample volume length and registration accuracy assessment in quality controls of PW Doppler diagnostic systems: a comparative study

In clinical diagnostics, Pulsed Wave (PW) Doppler is one of the most used spectral Doppler techniques since it provides quantitative information about the severity of several cardiac disorders. Therefore, routine quality control tests should be scheduled to check whether a proper level of performance is maintained over time. Despite continuous research in the field, performance evaluation of Doppler equipment is still an open issue. Therefore, the present study is focused on the comparative investigation based on a test parameter for the automatic analysis of faults in sample volume length and range gate registration accuracy. The Velocity Profile Discrepancy Index (VPDI) provides a quantitative estimation according to the agreement between the theoretical parabolic velocity profile and the measured one. The index was assessed through an automatic method that post-processes PW spectrogram images acquired at six sample volume depths with respect to the vessel radius of a Doppler reference device. Tests were repeated for three brand-new ultrasound diagnostic systems, equipped with convex and phased array probes, in two working conditions. From the analysis of the results, a lower discrepancy between the measured and the theoretical velocity profile was found for the convex array probes as well as a lower uncertainty contribution.

Modulation transfer function (MTF) evaluation for x-ray phase imaging system employing attenuation masks

Objective. Attenuation masks can be used in x-ray imaging systems to increase their inherent spatial resolution and/or make them sensitive to phase effects, a typical example being Edge Illumination x-ray phase contrast imaging (EI-XPCI). This work investigates the performance of a mask-based system such as EI-XPCI in terms of Modulation Transfer Function (MTF), in the absence of phase effects. Approach. Pre-sampled MTF measurements, using an edge, were performed on the same system implemented without masks, with non-skipped masks and finally with skipped masks (i.e. masks in which apertures illuminate every other pixel row/column). Results are compared to simulations and finally images of a resolution bar pattern acquired with all the above setups are presented. Main results. Compared to the detector’s inherent MTF, the non-skipped mask setup provides improved MTF results. In comparison to an ideal case where signal spill-out into neighbouring pixels is negligible, this improvement takes place only at specific frequencies of the MTF, dictated by the spatial repetition of the spill-out signal. This is limited with skipped masks, which indeed provide further MTF improvements over a larger frequency range. Experimental MTF measurements are supported through simulation and resolution bar pattern images. Significance. This work has quantified the improvement in MTF due to the use of attenuation masks and lays the foundation for how acceptance and routine quality control tests will have to be modified when systems using masks are introduced in clinical practice and how MTF results will compare to those of conventional imaging systems.

Fluorimetric Determination of Antiviral (COVID-19) Drug Favipiravir in Bulk and Pharmaceutical Dosage Forms

Favipiravir is a synthetic prodrug, which was first discovered while assessing the antiviral activity of chemical agents active against the influenza virus in the chemical library of Toyoma chemicals. It works by inhibiting RNA dependant RNA polymerase (RdRP), an enzyme required for RNA viral replication inside human cells. A simple, rapid, and economic method was developed for the quantitative determination of Favipiravirusing spectrofluorometer. The Favipiravir standard drug solution and sample tablet solution was prepared using double distilled water as a diluent. The different concentrations ofpure drugin the range 2-10 μg/ml and one sample solution were measured for the intensity at 432nm in the spectrofluorometer. The calibration curve was plotted and the sample’s unknown concentration was calculated from the plot. The calibration curve was found to be linear with r2 value obtained as 0.99.There are various other methods available for the quantification of Favipiravir which include RP-HPLC, UV-spectroscopic methods, FTIR, LC-MS with different extraction methods spiked in human plasma but not by using spectrofluorometer. Favipiravir shows fluorescence when dissolved in appropriate solvent hencethis method was developed to quantify Favipiravir which is a simple and efficient method. This method developed is easy and can be used for routine quality control test for Favipiravir pharmaceutical formulations.&#x0D; Keywords: Favipiravir, spectrofluorometer, Calibration curve.

Validated RP-HPLC Method for Simultaneous Estimation of Perphenazine and Amitriptyline in Bulk and Tablet Dosage form

A new, simple, precise, rapid, selective and stability reversed-phase high performance liquid chromatographic (RP-HPLC) method has been developed and validated for the simultaneous quantification of Perphenazine and Amitriptyline in pure form and its pharmaceutical dosage form. The method is based on Phenomenex Gemini C18 (4.6×250mm) 5µ column. The separation is achieved using isocratic elution by Methanol: TEA Buffer in the ratio of 65:35% v/v, pumped at flow rate 1.0mL/min and UV detection at 230nm. The column is maintained at 40°C throughout the analysis. The total run time is about 6min. The method is validated for specificity, accuracy, precision and linearity, robustness and ruggedness, system suitability, limit of detection and limit of quantitation as per International conference of harmonization (ICH) Guidelines. The method is accurate and linear for quantification of Perphenazine, Amitriptyline between 10 - 50µg/mL and 20 - 100µg/mL respectively. Further, satisfactory results are also established in terms of mean percent- age recovery (100.37% for Perphenazine and 100.34% for Amitriptyline, intra-day and inter-day precision (&lt;2%) and robustness. The advantages of this method are good resolution with sharper peaks and sufficient precision. The results indicate that the method is suitable for the routine quality control testing of marketed tablet formulations.

Authenticity Analysis of Cold-Pressed Orange Essential Oils by GC/MS on Polymethoxyflavone Components

Citrus essential oil combines numerous components with many qualities and control issues. For example, how to monitor volatile components and nonvolatile substances simultaneously is a major problem. Therefore, the objective of this study was to develop a Gas chromatography/mass spectrometry (GC/MS) method for the compositional study of total constituents in cold-pressed essential oils from major orange species. A polysiloxane GC column (DB-1, nonpolar, low-bleeding) was used in this study; its fingerprint includes terpenoids (Section 1), long-chain hydrocarbons (Section 2), phytosterols, and polymethoxyflavones (Section 3). These markers are more effective in detecting adulteration of essential oil products than volatile components, and more effective than quantitative PMF by 5α-Cholestane for establishing authenticity. The study aims to use the analysis procedure as a routine quality control test for authenticity evaluation in cold-pressed orange essential oils (CP-OrEO).

TLC–Densitometric Analysis of Selected 5-Nitroimidazoles

Metronidazole, ornidazole, tinidazole, and secnidazole are 5-nitroimidazoles. The purpose of this work was to propose a new economical TLC–densitometric method to evaluate the chemical stability of metronidazole, secnidazole, ornidazole, and tinidazole under stress conditions. A forced degradation study was performed on silica gel and aqueous solutions at various pH values; the metronidazole, secnidazole, ornidazole, and tinidazole solutions were prepared in saline and in hydrogen peroxide, respectively. The samples of the 5-nitroimidazoles were heated. TLC analyses were performed on silica gel 60F254 using chloroform–methanol (9:1, v/v) as the mobile phase. As the TLC–densitometric method can effectively separate the metronidazole, secnidazole, ornidazole, and tinidazole from their degradation products which formed as a result of the stress studies, it is considered to can be a good alternative and important tool in the routine quality control and stability testing of metronidazole, secnidazole, ornidazole, and tinidazole in pharmaceutical formulations. The results indicate that the proposed TLC–densitometric method is cost-effective, rapid, specific, accurate, and precise; the TLC–densitometric method also realizes the criterion of the linearity. A major advantage of the proposed method is its low cost and ability to analyze the 5-nitroimidazole which was investigated and all its degradation products simultaneously.

Development of a monoclonal antibody sandwich ELISA for the determination of antigen content and quality in diphtheria vaccines.

At present, quality control of diphtheria vaccines by both manufacturers and national control laboratories relies heavily on in vivo assays to confirm potency. As part of the VAC2VAC project we have developed a monoclonal antibody (mAb) enzyme-linked immunosorbent assay (ELISA) to measure the relative amount and quality of diphtheria toxoid (DTxd) in Diphtheria-Tetanus based vaccines, and believe this test has the potential to play a key role in a control strategy no longer including an in vivo potency test. The mAb ELISA is highly specific, has good dilutional linearity and is suitable for detecting DTxd in a range of different human vaccine products. We have demonstrated the ability of the assay to discriminate between batches of different content and quality using vaccine batches that had been prepared to contain differing amounts of DTxd or altered by exposure to heat or oxidative stress. We have also demonstrated successful transfer of the method to other laboratories and have shown that different diphtheria antigen materials may be able to serve as a reference antigen for local standardisation of the method. The assay is ideally suited for incorporation into a consistency approach for routine diphtheria vaccine quality control testing and may be suitable to serve as the stability indicating test in replacement of the current in vivo potency test.

Validated high‐performance thin layer chromatographic method for simultaneous quantification of rifampicin and quercetin in liquisolid formulation using fractional factorial design in robustness study

AbstractThe present research study focuses on the development of the high‐performance thin‐layer chromatographic method using the design of experiment approach for the simultaneous estimation of Rifampicin and Quercetin. Chromatographic separation was performed on Aluminium plates precoated with silica gel 60 F254 using chloroform:methanol:formic acid:ethyl acetate:benzene (4:1.8:0.3:1.7:1, v/v/v/v/v) as optimized mobile phase. A fractional factorial design was applied for the robustness study and the independent variables selected were mobile phase composition (A), solvent front (B), chamber saturation time (C), and wavelength (D). It was statistically revealed that the volume of ethyl acetate affected the Rf of both drugs resulting in stricter control of ethyl acetate volume compared to the other three variables. Rf for Rifampicin and Quercetin was 0.35 and 0.71 at 347 nm. The linear concentration range was 100–600 ng/band for both drugs. The %recovery ranged between 95.25% and 96.71% for Rifampicin and 95.33%–96.86% for Quercetin. The method was validated by determination of linearity, precision, accuracy, and specificity according to Q2(R1) guidelines, and the %relative standard deviation values were less than 2% for both drugs. A simple, accurate, and reproducible high‐performance thin‐layer chromatographic method was developed, for routine quality control testing of pharmaceutical formulation.

Accurate and efficient measurement of channelized Hotelling observer-based low-contrast detectability on the ACR CT accreditation phantom.

Current CT quality control (QC) for low-contrast detectability relies on visual inspection and measurement of contrast-to-noise ratio (CNR). However, CNR numbers become unreliable when it comes to nonlinear methods, such as iterative reconstruction (IR) and deep-learning-based techniques. Image quality metrics using channelized Hotelling observer (CHO) have been validated to be well correlated with human observer performance on phantom-based and patient-based tasks, but it has not been widely used in routine CT QC mainly because the CHO calculation typically requires a large number of repeated scans in order to provide accurate and precise estimate of index of detectability (d'). The main goal of this work is to optimize channel filters and other CHO parameters and accurately estimate the low-contrast detectability with minimum number of repeated scans for the widely used American College of Radiology (ACR) CT accreditation phantom so that it can become practically feasible for routine CT QC tests. To provide a converged d' value, an ACR phantom was repeatedly scanned 100 times at three dose levels (24, 12, and 6 mGy). Images were reconstructed with two kernels (FBP Br44 and IR Br44-3). d' as a function of number of repeated scans was determined for different number of background regions of interest (ROIs), different number of low-contrast objects, different number of slices per each object, and different channel filter options. A reference d' was established using the optimized CHO setting, and the bias of d' was quantified using the d' calculated from all 100 repeated scans. The variation of d' at each condition was estimated using a resampling method combining random subsampling among 100 repeated scans and bootstrapping of the ensembles of signal and background ROIs. Optimized parameters in CHO calculation were determined: two background ROIs per object, four objects per low-contrast object size, nine non-overlapping slices per object, and a 4-channel Gabor filter. The bias and uncertainty were estimated at different numbers of repeated scans using these parameters. When only one single scan was used in the CHO calculation, the bias of d' was below 6.2% and the uncertainty 15.6-19.6% for the 6, 5, and 4 mm objects, while with three repeated scans the bias was below 2.0% and uncertainty 8.7-10.9% for the three object sizes. With optimized parameter settings in CHO, efficient and accurate measurement of low-contrast detectability on the commonly used ACR phantom becomes feasible, which could potentially lead to adoption of CHO-based low-contrast evaluation in routine QC tests.

SEPARATION AND IDENTIFICATION OF FORCED DEGRADATION PRODUCTS OF LOFEXIDINE BY USING LC-MS/MS

Objectives: A rapid and reliable isocratic LC-MS/MS method was developed and validated for the separation and identification of stress degradation products (DPs) of lofexidine. Methods: Lofexidine, a non-opioid centrally acting alpha2-adrenergic receptor agonist, was subjected to hydrolysis (acidic, alkaline, and neutral), oxidation, photolysis, and thermal stress as per International Council on Harmonization specified conditions. The drug showed extensive degradation under alkaline, acidic, oxidation, and photolytic stress condition. Results: A total of 14 DPs were observed and the chromatographic separation of the drug and its DPs were achieved on waters symmetry C18 (150 × 4.6 mm, 3.5 μm) column using water and acetonitrile (75:25 v/v) as mobile phase. The DPs were separated and identified using LC-MS/MS. The LC-MS/MS method was validated with respect to specificity, linearity, accuracy, and precision. Conclusion: The proposed method was used for impurity profiling and routine quality control tests of lofixidine.

Quality by design assisted high‐performance liquid chromatography parameters for simultaneous estimation of simvastatin and fenofibrate

AbstractIn a present study quality by design was used to develop a reliable high‐performance liquid chromatography method for simultaneous estimation of simvastatin and fenofibrate. A robust chromatographic setting for quality peaks and appropriate component separation within a reasonable run duration was generated. Furthermore, to determine critical quality attributes (CQA), a quantitative relationship between critical material attributes and CQA was established using Box‐Behnken design to produce analytical design space and develop a control approach. The mathematical models used three independent characteristics, acetonitrile volume, buffer molarity, and flow rate. The optimum and expected conditions were acetonitrile and potassium dihydrogen orthophosphate buffer (pH 2.9 adjusted, with orthophosphoric acid) (80.65:19.35 v/v) as an optimized mobile phase at a flow rate of 0.99 ml/min. We achieved adequate baseline separation of both drugs in just 10 min with these optimum parameters. The amount of acetonitrile was revealed to be the most important factor determining the perturbation plot responses. The %recoveries for both medicines were 99.15%–101.86% at all three levels. Both drugs showed relative standard deviations for repeatability, and intermediate precision were less than 2%. As a result, a simple, accurate, and repeatable high‐performance liquid chromatography approach for routine quality control testing was developed.

Sickle cell trait results in a high leukoreduction quality control failure rate for whole blood donations.

BackgroundPrior studies have shown that sickle cell trait (SCT) is the most common reason attributed to leukoreduction (LR) filter failure due to physical blockage. However, current Food and Drug Administration (FDA) guidelines do not require blood collectors to take a specific action to mitigate inadequate LR that may occur among donors with SCT. We sought to determine the scope of inadequate LR among whole blood (WB) donations collected from individuals with SCT and processed under standard manufacturing conditions.Study Design and MethodsBetween 8/2021 and 2/2022, a total of 40 red blood cells units (RBCs) manufactured from WB donations collected from donors historically positive for SCT had residual leukocyte testing performed. All 40 of the units had appeared to successfully complete leukofiltration.ResultsOut of the 40 units tested, 22 failed routine residual leukocyte quality control testing (55% failure rate, 95% confidence interval 40%–70%). Nine out of the 22 failures resulted in more than 100 residual leukocytes per microliter of product.ConclusionEven when leukofiltration appears to have been completed successfully, WB units collected from donors with SCT have a high (55% in aggregate) rate of inadequate leukoreduction. Correlating this result with previous studies showing that of up to 50% of WB units collected from donors with SCT fail to pass through the leukoreduction filter, we estimate that only 25% of WB donations collected from individuals with SCT will result in a leukoreduced RBC unit that meets all FDA requirements. Blood centers should encourage individuals with SCT to donate platelets or plasma, rather than WB.

UV-Visible Spectrophotometric Method Development and Validation for the Estimation of Curcumin and Tetrahydrocurcumin

Background: Curcumin shows degradation in the solution of high pH. There is a need for development of a method which can estimate the drug release precisely and accurately. The UV spectroscopy due to its simplicity and specificity is the most popular for method development for the determination of drugs. Objective: The present study was aimed to develop the UV-Visible spectrophotometric method for the assessment of curcumin and tetrahydrocurcumin (THC) using a stable solvent system. Method: The solubility of curcumin and tetrahydrocurcumin was determined at various physiological pH levels. Non-ionic surfactant, tween 80 was used with selected media to avoid the degradation of drugs. The selected solvent system was further validated according to guidelines of the international conference on harmonization (ICH) and the analytical parameters like linearity, veracity, sensitivity and accuracy were studied. Results: The solvent systems Phosphate buffer of pH 6.8+2% tween 80 and Phosphate buffer of pH 6.8+1% tween 80 were found optimum for estimation of curcumin and THC respectively. All the validation parameters were found within the range for developed methods. Conclusion: The proposed method is very simple and can be used for routine quality control testing of curcumin and tetrahydrocurcumin.