Repeatability Coefficients Of Variation Research Articles

An isotope dilution-liquid chromatography-tandem mass spectrometry (ID-LC-MS/MS)-based candidate reference measurement procedure for the quantification of carbamazepine-10,11-epoxide in human serum and plasma.

A reference measurement procedure (RMP) using isotope dilution liquid chromatography-tandem mass spectrometry (ID-LC-MS/MS) was developed and validated with the aim of accurately measuring carbamazepine-10,11-epoxide concentrations in human serum and plasma. To establish traceability to SI units, the absolute content of the reference material was determined using quantitative nuclear magnetic resonance (qNMR) spectroscopy. As sample preparation a protein precipitation protocol followed by a high dilution step was established. Chromatographic separation from carbamazepine and potential metabolites was achieved using a C18 stationary phase. Selectivity, specificity, matrix effects, precision and accuracy, inter-laboratory equivalence, and uncertainty of measurement were evaluated based on guidelines from the Clinical and Laboratory Standards Institute, the International Conference on Harmonization, and the Guide to the Expression of Uncertainty in Measurement. The RMP demonstrated very good selectivity and specificity, showing no evidence of a matrix effect. This enabled accurate quantification of carbamazepine-epoxide in the concentration range of 0.0400-12.0 μg/mL. The intermediate precision was found to be less than 2.1 %, and the repeatability coefficient of variation (CV) ranged from 1.2 to 1.8 % across all concentration levels. Regarding accuracy, the relative mean bias varied from 1.4 to 2.5 % for native serum levels and from 1.4 to 3.5 % for Li-heparin plasma levels. The measurement uncertainty for single measurements ranged from 1.6 to 2.1 %. In this study, we introduce a new LC-MS/MS-based candidate RMP for accurately measuring carbamazepine-10,11-epoxide in human serum and plasma. This novel method offers a traceable and dependable platform, making itsuitable for standardizing routine assays and assessing clinically relevant samples.

Simultaneous determination of sulfonamides, trimethoprim, amoxicillin and tylosin in medicated feed by high performance liquid chromatography with mass spectrometry.

The article presents a rapid and simple analytical procedure for determination of four sulfonamides (sulfadiazine, sulfamerazine, sulfamethazine and sulfamethoxazole), trimethoprim, tylosin and amoxicillin in animal medicated feed. Eighteen medicated feed samples were analysed for active substances. The analytical protocol used a mixture of acetonitrile and 0.05 M phosphoric buffer, pH 4.5 for the extraction of seven antibacterial substances. After extraction, the samples were diluted in Milli-Q water and analysed by liquid chromatography with mass spectrometry. The developed procedure was subjected to validation in terms of linearity, selectivity, limits of quantification and determination, repeatability, reproducibility and uncertainty. The validation of the method was carried out in accordance with the criteria set out in Commission Implementing Regulation (EU) 2021/808 and ICH guidelines. This method provided average recoveries of 90.8 to 104.5% with coefficients of variation for repeatability and reproducibility in the ranges of 3.2-6.9% and 5.2-8.3%, respectively for all analysed antibacterial substances. The limit of detection and limit of quantification for all seven analytes ranged from 5.4 mg/kg to 48.3 mg/kg and from 10.4 mg/kg to 119.3 mg/kg, respectively. The uncertainty of the method depending on the compound varied from 14.0% to 24.0%. The validated method was successfully applied to the 18 medicated feeds. The developed method can be successfully used to routinely control the content and homogeneity of seven antibacterial substances in medicated feed.

An isotope dilution-liquid chromatography-tandem mass spectrometry (ID-LC-MS/MS)-based candidate reference measurement procedure (RMP) for the quantification of phenobarbital in human serum and plasma.

Phenobarbital serves as an antiepileptic drug (AED) and finds application in the treatment of epilepsy either as monotherapy or adjunctive therapy. This drug exhibits various pharmacodynamic properties that account for its beneficial effects as well as potential side effects. Accurate measurement of its concentration is critical for optimizing AED therapy through appropriate dose adjustments. Therefore, our objective was to develop and validate a new reference measurement procedure (RMP) for the accurate quantification of phenobarbital levels in human serum and plasma. A sample preparation protocol based on protein precipitation followed by a high dilution step was established in combination with a liquid chromatography-tandem mass spectrometry (LC-MS/MS) method using a C8 column to separate target analytes from known and unknown interferences. Assay validation and determination of measurement uncertainty were performed based on current guidelines. Selectivity and Specificity were assessed using spiked serum and plasma samples; to investigate possible matrix effects (MEs) a post-column infusion experiment and a comparison of standard line slopes was performed. Precision and accuracy were determined within a multiday precision experiment. The RMP was shown to be highly selective and specific, with no evidence of matrix interferences. It can be used to quantify phenobarbital in the range of 1.92 to 72.0 μg/mL. Intermediate precision was less than 3.2 %, and repeatability coefficient of variation (CV) ranged from 1.3 to 2.0 % across all concentration levels. The relative mean bias ranged from -3.0 to -0.7 % for native serum levels, and from -2.8 to 0.8 % for Li-heparin plasma levels. The measurement uncertainties (k=1) for single measurements and target value assignment were 1.9 to 3.3 % and 0.9 to 1.6 %, respectively. A novel LC-MS/MS-based candidate RMP for the quantification of phenobarbital in human serum and plasma is presented which can be used for the standardization of routine assays and the evaluation of clinically relevant samples.

A chemiluminescence immunoassay for type IV collagen as a promising marker for liver fibrosis and cirrhosis.

Herein, a magnetic bead-based chemiluminescence assay is reported to detect type IV collagen (col-IV) in serum samples. Magnetic beads (MBs) exhibit biocompatibility. Taking advantage of this property, they were conjugated with the col-IV antibody. For the determination of col-IV, the interaction of the col-IV sample, anti-(col-IV)-alkaline phosphatase (anti-(col-IV)-ALP) and anti-col-IV-magnetic beads (anti-(col-IV)-MBs) was performed to generate chemiluminescence. Under the optimized conditions, the developed method displayed good linearity in the concentration range of 20-2000 ng mL-1 with the limit of 0.79 ng mL-1. The repeatability coefficient of variation (CV) for col-IV detection ranged from 3.16% to 7.50%. The col-IV level in samples collected from a hospital was assessed by the chemiluminescence assay. Satisfactory recoveries were obtained ranging from 93.30% to 100.14%. In conclusion, the magnetic bead-based chemiluminescence assay may be used as a routine and efficient tool to detect type IV collagen in clinical diagnosis.

Determination of Trace Perchlorate in Soil using Liquid Chromatography-Tandem Mass Spectrometry (LC-MS/MS)

The international standard (IS) currently used for determining perchlorate in soil is not applicable to trace perchlorate. We developed a quantitative analysis method using liquid chromatography–tandem mass spectrometry (LC-MS/MS) for the trace perchlorate in soil. The perchlorate was extracted from air-dried soil (<150 μm) with distilled water. We proposed the optimum extraction method that included mechanical shaking followed by centrifugation. An internal standard material (Cl18O4-) was added to the extracts and standard solutions at concentration of 5 μg L-1. The samples were analyzed by LC-MS/MS equipped with a reversed phase C18 column packed with core-shell particles containing trimethylsilane functional groups. Samples that may be interfered with organic matter present in the soil should be purified with a C18 cartridge. The method detection limit and limit of quantitation for our method was 1.31 and 4.36 μg/kg, respectively. We verified the proposed method through interlaboratory comparison test; both coefficients of variation for repeatability (CVr) and reproducibility (CVR) were less than 5%. Therefore, we concluded that the proposed method may be used for precise quantitative analysis of trace amounts of perchlorate in soil.

Agreement, repeatability, and reproducibility of quantitative retinal layer assessment using swept-source and spectral-domain optical coherence tomography in eyes with retinal diseases.

To evaluate the agreement and precision of retinal thickness measurements obtained using swept-source optical coherence tomography (SS-OCT) and spectral-domain OCT (SD-OCT) in healthy eyes and eyes with retinopathy. This cross-sectional prospective study involved three DRI-OCT Triton (SS-OCT) and three 3D-OCT-1 Maestro (SD-OCT) devices. One of each device (Maestro and Triton) was paired with a single operator. Healthy subjects and patients with retinal diseases were recruited, with study eye and testing order randomized. At least 3 scans per eye were captured for wide scan (12 mm × 9 mm-Triton and Maestro) and macular cube scan (7 mm × 7 mm-Triton, 6 mm × 6 mm-Maestro). Thickness of the full retina, ganglion cell layer + inner plexiform layer (GCL+), and ganglion cell complex (GCL++) were obtained from wide scan and cube scans. Agreement of the measurements between the Triton and Maestro was evaluated by Bland-Altman analysis and Deming regression for each group. Repeatability and reproducibility were assessed using a two-way random effect analysis of variance (ANOVA) model for each parameter by group. Twenty-five healthy subjects (25 eyes) and 26 patients with retinal diseases (26 eyes), including, but not limited to, age-related macular degeneration, macular hole, and diabetic retinopathy were recruited. Overall, the measurement differences between Triton and Maestro were <6 μm (mean differences of full retina, GCL++, and GCL+ thickness were ≤5.5 μm, 1.3 μm, and 2.8 μm, respectively) and not statistically significant across the parameters. The repeatability and reproducibility estimates indicate high precision in both devices and groups. Across all the parameters, the repeatability limit was ≤7.6 μm for Triton and ≤12.7 μm for Maestro; reproducibility limit was ≤9.2 μm for Triton and ≤14.4 μm for Maestro. In eyes with retinal pathology, the repeatability coefficient of variation (CV)% was ≤2.6% for Triton and ≤3.4% for Maestro; reproducibility CV% was ≤3.3% for Triton and ≤3.5% for Maestro. Both Triton SS-OCT and Maestro SD-OCT provide reliable measurements of retinal thickness in healthy eyes and eyes with retinal diseases. Excellent agreement between the two devices indicates interoperability when testing healthy eyes or eyes with retinal pathology. These findings support the use of thickness measurements from Triton SS-OCT and Maestro SD-OCT in clinical practice.

Verification of the analytical performance of the serum glucose assay on the Abbott Alinity ci®

The precision and reliability of the serum glucose assay on the Abbott Alinity ci® analyzer were systematically evaluated. The study was conducted over 30 days in the biochemistry laboratory of Mohammed VI University Hospital. Two phases were carried out: reproducibility assessment involving daily measurements across low, medium, and high glucose levels, and repeatability testing involving 30 replicates per sample. The hexokinase enzymatic approach was employed for glucose quantification. Data analysis utilized the BYG middleware and complied with FSCB and RICOS standards. For reproducibility, the coefficient of variation (CV) values were low, ranging from 1.49% to 1.84%. Repeatability CV values were even lower, varying from 0.34% to 0.94%. Results aligned well with quality control limits, confirming the assay's consistency and precision. This study underscores the robustness and reliability of the hexokinase method on the Alinity ci® platform for serum glucose analysis, with implications for accurate patient care. By adhering to strict analytical performance verification, laboratories ensure dependable clinical outcomes. This research contributes to the foundation of knowledge supporting serum glucose measurement reliability.

Quantitative Detection of House Dust Mites-Specific IgE by Light-Initiated Chemiluminescence Assay.

To establish a new method for quantitative detection of house dust mite (HDM)-sIgE based on light-initiated chemiluminescence assay (LiCA). The assay was established after optimizing the reaction conditions, and the assay performance was evaluated according to the clinical guidelines. Further, the results of LiCA were compared with those from the ELISA and ImmunoCAP methods. Coefficients of variation for repeatability ranged from 4.22% to 7.69%, and intermediate precision from 8.38% to 10.34%. The limit of blank (LoB), limit of detection (LoD), and limit of quantitation (LoQ) were 0.066 kUA/L, 0.165 kUA/L, and 0.171 kUA/L, respectively. The coefficient of correlation (r) between the results of LiCA and ELISA was 0.9263, and the r between the results of LiCA and ImmunoCAP was 0.8870. A HDM-sIgE quantitation assay based on LiCA was established, which could be used as a new reliable analytical tool for the determination of HDM-sIgE.

Establishment and analytical performance of light-initiated chemiluminescence assay method for detecting thyrotropin receptor antibody.

Aim: To evaluate double-antibody competitive light-initiated chemiluminescence assay method for detecting the thyrotropin receptor antibody. Materials & methods: The optimal working concentrations of competitive antibody and rTSHR were confirmed by checkerboard titration. Assay performance was assessed by precision, linearity, accuracy, limit of blank and clinical evaluation. Results: The coefficient of variation for repeatability and intermediate precision was 3.9-5.9 and 0.9-1.3%, respectively. The correlation coefficient was 0.999 by least squares linear fitting in linearity evaluation. The relative deviation ranged from -5.9 to 4.1%, and the limit of blank of the method was 0.13IU/l. Compared with the Roche cobas system(Roche Diagnostics, Mannheim, Germany), the relationship between the two assays was shown to be significantly correlative. Conclusion: The light-initiated chemiluminescence assay method for detecting thyrotropin receptor antibody is a rapid, novel and accurate method for thyrotropin receptor antibody measurement.

An isotope dilution-liquid chromatography-tandem mass spectrometry (ID-LC-MS/MS)-based candidate reference measurement procedure (RMP) for the quantification of gabapentin in human serum and plasma.

To describe and validate a reference measurement procedure (RMP) for gabapentin, employing quantitative nuclear magnetic resonance (qNMR) spectroscopy to determine the absolute content of the standard materials in combination with isotope dilution-liquid chromatograph-tandem mass spectrometry (ID-LC-MS/MS) to accurately measure serum and plasma concentrations. A sample preparation protocol based on protein precipitation in combination with LC-MS/MS analysis using a C8 column for chromatographic separation was established for the quantification of gabapentin. Assay validation anddetermination of measurement uncertainty were performed according to guidance from the Clinical and Laboratory Standards Institute, the International Conference on Harmonization, and the Guide to the expression of uncertainty in measurement. ID-LC-MS/MS parameters evaluated included selectivity, specificity, matrix effects, precision and accuracy, inter-laboratory equivalence, and uncertainty of measurement. The use of qNMR provided traceability to International System (SI) units. The chromatographic assay was highly selective, allowing baseline separation of gabapentin and the gabapentin-lactam impurity, without observable matrix effects. Variability between injections, preparations, calibrations, and days (intermediate precision) was <2.3%, independent of the matrix, while the coefficient of variation for repeatability was 0.9-2.0% across all concentration levels. The relative mean bias ranged from-0.8-1.0% for serum and plasma samples. Passing-Bablok regression analysis indicated very good inter-laboratory agreement; the slope was 1.00 (95% confidence interval [CI] 0.98 to 1.03) and the intercept was-0.05 (95% CI -0.14 to 0.03). Pearson's correlation coefficient was≥0.996. Expanded measurement uncertainties for single measurements were found to be≤5.0% (k=2). This analytical protocol for gabapentin, utilizing traceable and selective qNMR and ID-LC-MS/MS techniques, allows for the standardization of routine tests and the reliable evaluation of clinical samples.

Evaluation of automated calibration and quality control processes using the Aptio total laboratory automation system

Background: The objective of this study was to determine whether manually performed calibration and quality control (QC) processes could be replaced with an automated laboratory system when installed analyzers fail to provide automated calibration and QC functions.Methods: Alanine aminotransferase (ALT), total cholesterol (TC), creatinine (Cr), direct bilirubin (DB), and lipase (Lip) items were used as analytes. We prepared pooled serum samples at 10 levels for each test item and divided them into two groups; five for the analytical measurement range (AMR) group and five for the medical decision point (MDP) group. Calibration and QC processes were performed for five consecutive days, and ALT, TC, Cr, DB, and Lip levels were measured in the two groups using automated and manual methods. Precision and the mean difference between the calibration and QC methods were evaluated using the reported values of the test items in each group.Results: Repeatability and within-laboratory coefficients of variation (CVs) between the automated system and the conventional manual system in the AMR group were similar. However, the mean reported values for test items were significantly different between the two systems. In the MDP group, repeatability and within-laboratory CVs were better with the automation system. All calibration and QC processes were successfully implemented with the Aptio total laboratory automation system.Conclusion: The Aptio total laboratory automation system could be applied to routine practice to improve precision and efficiency.

MR Fingerprinting for Liver Tissue Characterization: A Histopathologic Correlation Study.

Background Liver MR fingerprinting (MRF) enables simultaneous quantification of T1, T2, T2*, and proton density fat fraction (PDFF) maps in single breath-hold acquisitions. Histopathologic correlation studies are desired for its clinical use. Purpose To compare liver MRF-derived metrics with separate reference quantitative MRI in participants with diffuse liver disease, evaluate scan-rescan repeatability of liver MRF, and validate MRF-derived measurements for histologic grading of liver biopsies. Materials and Methods This prospective study included participants with diffuse liver disease undergoing MRI from July 2021 to January 2022. Participants underwent two-dimensional single-section liver MRF and separate reference quantitative MRI. Linear regression, Bland-Altman plots, and coefficients of variation were used to assess the bias and repeatability of liver MRF measurements. For participants undergoing liver biopsy, the association between mapping and histologic grading was evaluated by using the Spearman correlation coefficient. Results Fifty-six participants (mean age, 59 years ± 15 [SD]; 32 women) were included to compare mapping techniques and 23 participants were evaluated with liver biopsy (mean age, 52.7 years ± 12.7; 14 women). The linearity of MRF with reference measurements in participants with diffuse liver disease (R2 value) for T1, T2, T2*, and PDFF maps was 0.86, 0.88, 0.54, and 0.99, respectively. The overall coefficients of variation for repeatability in the liver were 3.2%, 5.5%, 7.1%, and 4.6% for T1, T2, T2*, and PDFF maps, respectively. MRF-derived metrics showed high diagnostic performance in differentiating moderate or severe changes from mild or no changes (area under the receiver operating characteristic curve for fibrosis, inflammation, steatosis, and siderosis: 0.62 [95% CI: 0.52, 0.62], 0.92 [95% CI: 0.88, 0.92], 0.97 [95% CI: 0.96, 0.97], and 0.74 [95% CI: 0.57, 0.74], respectively). Conclusion Liver MR fingerprinting provided repeatable T1, T2, T2*, and proton density fat fraction maps in high agreement with reference quantitative mapping and may correlate with pathologic grades in participants with diffuse liver disease. © RSNA, 2022 Online supplemental material is available for this article.

Validation of lipid profile measurement methods and establishment of reference values in a sub-Saharan African population.

Validated reference values and procedures are needed to ensure optimal diagnosis of dyslipidemia in sub-Saharan Africa. We aimed to validate an analysis method and establish reference intervals of lipid profile parameters in Cameroonians using this method. On a cross-sectional study conducted from November 2019 to August 2020 in Yaoundé, we have analyzed blood samples with Cobas® 6000. We subscribed to ASQUALAB's External Quality Assessments (EQA) and Outsourced Internal Quality Controls (IQC). Reproducibility, repeatability, correctness accuracy and uncertainty were evaluated using IQC. Consenting adult participants were conveniently sampled, excluding those with any condition that may affect lipid profile. Descriptive statistics were reported accordingly, agreement was assessed with Bland-Altman analysis, and reference intervals were defined according to CLSI and IFCC recommendations. The coefficients of variation for repeatability, reproducibility, and correctness bias ranged between 0.6% and 6%, with all values within the normal range. Expanded uncertainty of total cholesterol, HDL and triglycerides measurements were, respectively, 0.45, 0.24 and 0.18. We included 422 participants with a mean age of 30.2 (10.9) years and 248 (58.8%) females. Reference intervals for total cholesterol, HDL, triglycerides and LDL were, respectively, 2.94-6.02 mmol/L, 0.90-2.06 mmol/L, 0.35-1.36 mmol/L, 1.37-4.13 mmol/L. These intervals were similar between sex and ethnic groups, but lower in younger participants. Lipid profile measurement with Cobas® 6000 is a reliable and accurate analysis in our context. Specific reference intervals must be used in African population, with further studies need for different age subgroups.

Simultaneous Corneal Topography and Epithelial Thickness Mapping from a Single Measurement Using Optical Coherence Tomography.

Purpose To evaluate the performance of corneal epithelial thickness mapping (ETM) and demonstrate simultaneous measurement of ETMs and corneal topography using REVO NX (Optopol Technology, Zawiercie, Poland)—an OCT device for anterior and posterior segment imaging. Methods One hundred thirty-seven eyes of 137 normal subjects and patients with corneal diseases were recruited to the study. Each subject was scanned with REVO NX. ETMs and corneal topography maps were reconstructed from a single measurement. Corneal topography was also carried out using Pentacam (Oculus, Wetzlar, Germany). One hundred twenty-eight eyes were qualified for the final analysis. Forty healthy eyes were used to evaluate the performance of ETM, and 88 eyes were used to compare ETMs and corneal topography. The repeatability and reproducibility of ETMs in healthy subjects were assessed on the basis of 17 spatial zones derived from an 8-mm diameter corneal scan using within-subject standard deviation, test-retest repeatability, within-subject coefficient of variation (CoV), and intraclass correlation coefficient (ICC). Results The ICC for both repeatability and reproducibility of ETMs for the central sector was 0.95. The ICC value for the other sectors was only moderately lower. However, the CoV for repeatability (≤1.55%) was slightly higher than the value reported for the RTVue device (Optovue, Inc, Fremont, California, USA), for which a CoV in the central zone of 1.07% was reported in unoperated eyes. The superior quadrants were found to be the thinnest while the inferior ones were the thickest. ETMs and topography maps created from a single OCT measurement present a complementary image of the cornea. Conclusions ETMs obtained using REVO NX show high levels of repeatability and reproducibility in normal eyes. Because the topographic and epithelial thickness analyses are performed using the same data, which means they are based on the exact same 3D corneal model, they do not require reciprocal centration and map matching. This ensures a complete point-to-point correlation between ETMs and corneal topography maps, which paints a fuller picture of a given pathology.

Physicochemical stability of cefiderocol, a novel siderophore cephalosporin, in syringes at 62.5 mg/mL for continuous administration in intensive care units

IntroductionCefiderocol is a new siderophore time-dependent antibiotic of last resort. The manufacturer reports a stability of 6 hours for the infusion solution diluted in normal saline (NS) or dextrose 5%...

Evaluation of a Nanoparticle-Based Busulfan Immunoassay for Rapid Analysis on Routine Clinical Analyzers.

Busulfan is an alkylating agent used in allogeneic hematopoietic stem cell transplantation for various malignant and nonmalignant disorders. Therapeutic drug monitoring of busulfan is common because busulfan exposure has been linked to veno-occlusive disease, disease relapse, and failed engraftment. The authors developed an automated immunoassay, along with stable calibrators and controls, and quantified busulfan in sodium heparin plasma. The authors evaluated a homogenous nanoparticle immunoassay, the MyCare Oncology Busulfan Assay Kit (Saladax Biomedical, Inc), for precision, sensitivity, accuracy, and linearity on an open channel clinical chemistry analyzer; they compared the method with 2 mass spectrometry methods (liquid chromatography-tandem mass spectrometry and gas chromatography/mass spectrometry), using anonymized, remnant patient samples. The coefficients of variation for repeatability and within-laboratory precision were ≤9.0%. The linear range was 150-2000 ng/mL; samples up to 6000 ng/mL can be measured with sample dilution. Measured values deviated by ≤14% from assigned values. Comparison between validated mass spectrometry methods resulted in a correlation coefficient R ≥ 0.995. The MyCare Busulfan Assay Kit shows the precision, accuracy, linearity, and test range for performing busulfan concentration measurements in sodium heparin plasma on routine clinical chemistry analyzers.

Clinical Validation of an Automated Fluorogenic Factor XIII Activity Assay Based on Isopeptidase Activity.

Hereditary factor XIII (FXIII) deficiency is a rare autosomal bleeding disorder which can cause life-threatening bleeding. Acquired deficiency can be immune-mediated or due to increased consumption or reduced synthesis. The most commonly used screening test is insensitive, and widely used quantitative assays have analytical limitations. The present study sought to validate Technofluor FXIII Activity, the first isopeptidase-based assay available on a routine coagulation analyser, the Ceveron s100. Linearity was evidenced throughout the measuring range, with correlation coefficients of >0.99, and coefficients of variation for repeatability and reproducibility were <5% and <10%, respectively. A normally distributed reference range of 47.0–135.5 IU/dL was derived from 154 normal donors. Clinical samples with Technofluor FXIII Activity results between 0 and 167.0 IU/dL were assayed with Berichrom® FXIII Activity, a functional ammonia release assay, and the HemosIL™ FXIII antigen assay, generating correlations of 0.950 and 0.980, respectively. Experiments with a transglutaminase inhibitor showed that Technofluor FXIII Activity can detect inhibition of enzymatic activity. No interference was exhibited by high levels of haemolysis and lipaemia, and interference by bilirubin was evident at 18 mg/dL, a level commensurate with severe liver disease. Technofluor FXIII Activity is a rapid, accurate and precise assay suitable for routine diagnostic use with fewer interferents than ammonia release FXIII activity assays.

Experience in Validation of Methods for Determination of Radiochemical Impurities in Radiopharmaceuticals

Most important quality attributes of any radiopharmaceutical (RPh) are its radiochemical purity (RCP) or content of radiochemical impurities (RCIs) that have to comply with respective norms and limits. However, at present, there is no unified approach to validation of analytical methods in the context of highly radioactive samples.The aim of the study was to develop an approach to validation of methods for determination of RCI content in RPhs.Materials and methods: the authors determined the content of RCIs in a radiopharmaceutical formulation containing a complex of technetium-99m and methylenediphosphonic acid by the radiometric method after isolation of impurities from the main compound by thin-layer chromatography using silica gel and methyl ethyl ketone (for sodium pertechnetate determination) and silica gel and 13.6% sodium acetate solution (for determination of hydrolysed reduced technetium-99m). The radioactivity was registered by a chromatogram scanner with a detector of gamma-rays with energies from 0.05 to 1.5 MeV.Results: the paper analyses existing official approaches to validation of analytical procedures and compares them with the results of experimental studies described in available publications. It assesses the validation parameters for compliance with the acceptance criteria set forth in the current regulations and substantiates selectivity of chromatographic determination of impurities under the selected test conditions. Coefficients of variation for repeatability, reproducibility, and accuracy did not exceed 4.5, 2.8, and 8.9%, respectively, given the relative error of not more than 10.5%. The study demonstrated signal linearity for the 10-fold dilution of the standardised sodium pertechnetate solution, it also demonstrated correspondence between the applied and detected radioactivity when performing the test in the impurity content range of 0.5–5%. The validation procedure was associated with significant radiation burden for the personnel of the quality control laboratory.Conclusions: the authors suggested a methodological approach to validation of methods for determination of RCI content in technetium-99m-based RPhs. This approach may be used in the development of a guideline on validation of analytical methods for RCP/RCI determination in RPhs, or for introduction of relevant sections into existing documents.

The occurrence of mycotoxins in food collected from some northern provinces of Vietnam in 2019

This study investigated the content of aflatoxin, ochratoxin A, zearalenone, deoxynivalenol and fumonisin B1 in some food product. Samples were extracted and cleaned by QUEChERS approach. The extract was measured by liquid chromatography tandem mass spectrometry. The positive samples were reconfirmed by standard methods using immunoaffinity extraction. The detection limit of the method for aflatoxin, fumonisin B1, ochratoxin A, deoxynivalenol, zearalenone were 0.5, 30, 0.5, 60, and 3.0 &amp;micro;g/kg, respectively. The recoveries of all analytes were in the range of 70 - 110%. The repeatability coefficient of variation were in the range of 5,1 - 13%. Among the 300 food samples tested, there were 43 samples detected with studied mycotoxins, accounting for 14.3%, mainly focusing on unprocessed cereals. In which, 10 spice samples, 04 peanuts and sesame samples, 01 candy sample, 01 sample of nutritious cereal flour, and 01 food supplement sample were found to be contaminated with aflatoxin, ochratoxin A exceeding the maximum level of Ministry Of Health according to QCVN 8-1 : 2011/BYT.

Development and validation of confirmatory LC–MS/MS method for multi-residue analysis of antibiotic drugs in bovine milk

A confirmatory multi-class LC–MS/MS method have been developed for simultaneous determination of 23 antibiotic drugs from seven different classes in bovine milk. The method was validated in accordance with the criteria prescribed in Commission Decision 2002/657/EC. The linear regression analysis showed good correlation with R2 > 0.9800. LOD are in the range of 0.17–6.94 ng/ml, while the LOQ are in the range of 0.50–22.71 ng/ml. The CCα range from 4.43 to 122.33 ng/mL and CCβ was from 4.88 to 139.78 ng/mL. The recovery of the method ranged from 71.96 to 108.70%. The coefficient of variation for repeatability varied from 1.08 to 20.28% and the coefficient of reproducibility varied from 3.14 to 22.88%. In the present study, 189 bovine milk samples were collected from dairy farms and analyzed using confirmatory multi-class LC–MS/MS method. A total of 14 (7.41%) samples were found positive for antibiotics and sulfonamides. The concentrations of the residues were below the maximum levels established by EU.