Study of the parameters of absorption into the bloodstream and excretion of the drug Gamavit after a single administration to laboratory mini-pigs

A pharmacokinetic study of the absorption into the bloodstream, bioavailability and excretion of Gamavit from the body after intramuscular administration to laboratory mini-pigs was conducted. Quantitative determination was carried out by HPLC using a fluorimetric detector, for which Gamavit was labeled with Cy5 dye, which was then used for mini-pigs inoculation. The developed methods for determining Gamavit in the blood and feces were validated according to the following validation parameters: selectivity, calibration curve, accuracy, precision, limit of quantitative determination, sample transfer, and sample stability. The confirmed analytical range of the method for Gamavit detection in blood plasma and feces was 1.00…50.0 mcg/ml. Maximum concentration of Gamavit in the blood of mini-pigs after a single intramuscular injection was 30.97 mcg/ml and was reached on average 15 minutes after administration. 24 hours following administration, Gamavit was still detected in the blood in insignificant amounts. The average half-life of Gamavit in the blood is 8.64±3.50 hours. After administration at a dose of 0.1 ml/kg, the clearance of the drug is 1.27 l/kg * h, the excretion rate at an effective concentration of 30 mg/l is 38 mg/kg*h, and the maintenance dose when using the drug 1 time a day is 0.9…1.0 ml. The detection of the label in the feces of the studied animals indicates that one of the ways Gamavit removal is excretion with the help of bile acids, as well as partial excretion with feces.

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The Development of a Turbidimetric Method for the Quantitative Determination of Antibiotics of the Aminoglycoside Group in Medications

Antibiotics and Chemotherapy ◽

10.37489/0235-2990-2020-65-7-8-37-41 ◽

2020 ◽

Vol 65 (7-8) ◽

pp. 37-41

Author(s):

E. N. Semenova ◽

S. I. Kuleshova ◽

E. I. Sakanyan

Keyword(s):

Quantitative Determination ◽

Quality Assessment ◽

Aminoglycoside Antibiotics ◽

Metrological Characteristics ◽

Streptomycin Sulfate ◽

Turbidimetric Method ◽

Validation Criteria ◽

Validation Parameters ◽

Validation Tests

A method for the quantitative determination of streptomycin sulfate in medicines by the turbidimetric method has been developedand validated. Based on the results of the experiments, it was found that the metrological characteristics of such validation parameters of the method as linearity, precision, and correctness do not exceed the validation criteria. Linearity was noted in the range of streptomycin concentrations from 3.75 to 8.43 μg/ml. The results of validation tests of the method for the quantitative determination of streptomycin indicate the prospects and feasibility of introducing the turbidimetric method into the domestic system for standardization and quality assessment of aminoglycoside antibiotics.

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Validation method for body-mounted sensor attachments

Current Directions in Biomedical Engineering ◽

10.1515/cdbme-2020-2006 ◽

2020 ◽

Vol 6 (2) ◽

Author(s):

Katharina Schmidt ◽

David Hochmann

Keyword(s):

Evaluation Method ◽

Tracking System ◽

The Body ◽

Exploratory Research ◽

Body Segment ◽

Validation Method ◽

Sensor Position ◽

Validation Parameters ◽

Measurement Units ◽

Soft Tissue Artifact

AbstractSmall sensor devices like inertial measurement units enable mobile movement and gait analysis, whereby existing systems differ in data acquisition, data processing, and gait parameter calculation. Concerning the validation, recent studies focus on the captured motion and the influence of sensor positioning with respect to the accuracy of the computed biomechanical parameters in comparison to a reference system. Although soft tissue artifact is a major source of error for skin-mounted sensors, there are no investigations regarding the relative movement between the body segment and sensor attachment itself. The aim of this study is to find an evaluation method and to determine parameters that allow the validation of various sensor attachment types and different sensor positionings. The analysis includes the comparison between an adhesive and strap attachment variant as well as the frontal and lateral sensor placement. To validate different attachments, an optical marker-based tracking system was used to measure the body segment and sensor position during movement. The distance between these two positions was calculated and analyzed to determine suitable validation parameters. Despite the exploratory research, the results suggest a feasible validation method to detect differences between the attachments, independent of the sensor type. To have representative and statistically validated results, further studies that involve more participants are necessary.

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Determination of Alkali-Sensing Parts of the Insulin Receptor-Related Receptor Using the Bioinformatic Approach

Acta Naturae ◽

10.32607/20758251-2015-7-2-80-86 ◽

2015 ◽

Vol 7 (2) ◽

pp. 80-86 ◽

Cited By ~ 10

Author(s):

I. E. Deyev ◽

N. V. Popova ◽

A. G. Petrenko

Keyword(s):

Growth Factor ◽

Insulin Receptor ◽

Growth Factor Receptor ◽

Ph Sensitive ◽

Effective Concentration ◽

The Body ◽

Insulin Like Growth Factor ◽

Extracellular Region ◽

Half Maximal Effective Concentration ◽

Receptor Family

IRR (insulin receptor-related receptor) is a receptor tyrosine kinase belonging to the insulin receptor family, which also includes insulin receptor and IGF-IR receptor. We have previously shown that IRR is activated by extracellular fluid with pH 7.9 and regulates excess alkali excretion in the body. We performed a bioinformatic analysis of the pH-sensitive potential of all three members of the insulin receptor family of various animal species (from frog to man) and their chimeras with swapping of different domains in the extracellular region. An analysis using the AcalPred program showed that insulin receptor family proteins are divided into two classes: one class with the optimal working pH in the acidic medium (virtually all insulin receptor and insulin-like growth factor receptor orthologs, except for the IGF-IR ortholog from Xenopus laevis) and the second class with the optimal working pH in the alkaline medium (all IRR orthologs). The program had predicted that the most noticeable effect on the pH-sensitive property of IRR would be caused by the replacement of the L1 and C domains in its extracellular region, as well as the replacement of the second and third fibronectin repeats. It had also been assumed that replacement of the L2 domain would have the least significant effect on the alkaline sensitivity of IRR. To test the in silico predictions, we obtained three constructs with swapping of the L1C domains, the third L2 domain, and all three domains L1CL2 of IRR with similar domains of the insulin-like growth factor receptor. We found that replacement of the L1C and L1CL2 domains reduces the receptors ability to be activated with alkaline pH, thus increasing the half-maximal effective concentration by about 100%. Replacement of the L2 domain increased the half-maximal effective concentration by 40%. Thus, our results indicate the high predictive potential of the AcalPred algorithm, not only for the pH-sensitive enzymes, but also for pH-sensitive receptors.

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Treatment of cattle pyroplasmidosis in the conditions of Dagestan Republic

Agrarian science ◽

10.32634/0869-8155-2021-349-5-8-10 ◽

2021 ◽

Vol 344 (5) ◽

pp. 8-10

Author(s):

S. Sh. Abdulmagomedov ◽

A. Yu. Aliev ◽

R. M. Bakrieva ◽

E. A. Belkin

Keyword(s):

Live Weight ◽

The Body ◽

Control Measures ◽

Ixodid Ticks ◽

Farm Animals ◽

Blood Parasites ◽

Control Group ◽

Single Intramuscular Injection ◽

Short Time ◽

And Control

Relevance. Dagestan Republic in terms of natural and climatic characteristics is the most favorable for the of ixodid ticks - carriers of pathogens of blood-parasitic diseases of farm animals. In this regard, further improvement of the set of scientifically grounded control measures and the search for new promising chemotherapeutic drugs of the prevention and treatment of pyroplasmidosis of cattle are major problem of great national economic importance.Materials and methods. The studies were carried out in farms, unfavorable on pyroplasmidosis, in the conditions of Dagestan Republic. The object of the study was cattle, spontaneously invaded by various types of blood parasites. Experеmental and control groups in production experiments were selected according to the principle of analogues. In the first control group (n = 10) the drug was not used. The second (n = 10) was injected with the drug DAC 5% at a dose of 1 ml/20 kg (DV 2.5 mg/kg), intramuscularly, at the rate 5 ml per 100 kg of live weight. The animals of the third (n = 10) were injected with the injectable preparation forticarb 10% at a dose of 4 ml/100 kg (DV 4 mg/kg) of live weight, intramuscularly, once.Results. It was found that with a single intramuscular injection of forticarb at the rate 2 ml/50 kg of live weight, the temperature and parasitic reaction in the body of sick animals decreased in a very short time. Therapeutic efficacy in pyroplasmidosis of cattle was 90%.

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P0301FIT FOR PURPOSE VALIDATION OF A CLINICAL ASSAY FOR THE DETECTION OF SERUM LEVELS OF GALACTOSE-DEFICIENT IMMUNOGLOBULIN A1 (GD-IGA1) IN PATIENTS WITH IGA NEPHROPATHY (IGAN)

Nephrology Dialysis Transplantation ◽

10.1093/ndt/gfaa142.p0301 ◽

2020 ◽

Vol 35 (Supplement_3) ◽

Author(s):

Laura Sponton ◽

Hulin Jin ◽

Markus Fluck ◽

Yusuke Suzuki ◽

Amy Kao

Keyword(s):

Quantitative Determination ◽

Human Serum ◽

Iga Nephropathy ◽

Calibration Curve ◽

Clinical Studies ◽

Serum Samples ◽

Freeze Thaw ◽

Healthy Donors ◽

Validation Parameters

Abstract Background and Aims Analysis of serum or plasma from patients with IgA nephropathy (IgAN) has confirmed the presence of elevated levels of circulating immune complexes containing Gd-IgA1 (Czerkinsky 1986). New sensitive and reasonably specific noninvasive tests are emerging to guide the therapeutic strategy that is applicable to all stages of IgAN (Suzuki 2014). Here we are reporting the fit for purpose validation of an ELISA method for the quantitative determination of Gd-IgA1 in human serum samples to support biomarker investigations in clinical studies of Merck KGaA, Darmstadt. Method The assay was developed based on a commercially available immunoassay kit. The dynamic range of the calibration curve was determined from 1.56 ng/mL (LLOQ) to 100 ng/mL (ULOQ). With a minimum required dilution of 200-fold and standard assay volume of 50.0 μL, the range of the method in matrix was from 312 ng/mL to 20, 000 ng/mL. In assay validation phase, multiple validation parameters were evaluated, which included minimum required dilution (MRD), calibration curve, matrix effect, Intra- & Inter run accuracy & precision, selectivity, and parallelism. Additional validation parameters include sample stability (short/long term, freeze-thaw) and batch-to-batch comparison. Results All samples measured for intra & Inter - assay precision, accuracy, fulfilled the specifications according to the acceptance criteria. The selectivity was assessed using blank serum matrix from 10 individuals: the result indicated that matrix components in serum did not interfere with the detection of Gd-IgA1. Parallelism assessment was performed successfully for both samples from healthy donors and IgAN patient samples up to dilution factor (DF) 3200 (serum samples from healthy donors were determined up to DF 1600). All DF-corrected results within the assay range were determined with %CV ≤ 30.0%. Batch to batch comparison was assessed successfully based on the known shelf life of the kit. Short term stability using QC samples were given for up to 24hrs at room temperature. Freeze-thaw stability was given for up to 3 cycles at -20°C±5°C and -75°C±15°C. The investigations were performed according to general guidelines for method validation and applicable regulations. The results of investigated validation parameters fulfilled the requirements and recommendations, generally accepted for bioanalytical projects. Conclusion The present validation qualified the method for the quantitative determination of Gd-IgA1 in human serum samples from clinical studies.

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New Liquid Chromatographic Method for Determination of Rabeprazole Sodium in Coated Tablets

Journal of AOAC International ◽

10.1093/jaoac/87.4.842 ◽

2004 ◽

Vol 87 (4) ◽

pp. 842-846 ◽

Cited By ~ 6

Author(s):

Cássia V Garcia ◽

Clésio S Paim ◽

Martin Steppe

Keyword(s):

Quantitative Determination ◽

Proton Pump ◽

Chromatographic Method ◽

Array Detector ◽

Liquid Chromatographic Method ◽

Relative Standard ◽

Validation Parameters ◽

Rabeprazole Sodium ◽

Liquid Chromatographic

Abstract Rabeprazole sodium is a proton pump inhibitor that covalently binds and inactivates the gastric parietal cell proton pump (H+/K+ ATPase). Little has been published about the quantitative determination of this drug. The aim of this research was to develop a new liquid chromatographic method for quantitative determination of rabeprazole in coated tablets. The system consisted of a Hypersil Keystone Betabasic C8 column (250 × 4.6 mm, 5 μm particle size), an isocratic acetonitrile–water (35 + 65) mobile phase at a flow rate of 1.0 mL/min, and a diode array detector set at 282 nm. The following validation parameters were evaluated: linearity, precision, accuracy, specificity, detection and quantitation limits, and robustness. The method showed good linearity in the concentration range of 10–70 μg/mL. The quantitation limit was 2.43 μg/mL, and the detection limit was 0.80 μg/mL. The intra- and interday precision data showed that the method has good reproducibility (relative standard deviation = 1.03). Accuracy and robustness were also evaluated, and the results were satisfactory. The mean recovery was 101.61%. The analysis of a placebo mixture demonstrated the method is also specific.

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Development and Validation of Method for the Quantitative Determination of Zinc in its Chelate Complexes Using Energy Dispersive X-ray Fluorescence Spectroscopy

Drug development & registration ◽

10.33380/2305-2066-2021-10-4-154-161 ◽

2021 ◽

Vol 10 (4) ◽

pp. 154-161

Author(s):

А. V. Marukhlenko ◽

Т. V. Maksimova ◽

Т. V. Pleteneva ◽

М. A. Morozova

Keyword(s):

Fluorescence Spectroscopy ◽

Aqueous Solutions ◽

Quantitative Determination ◽

Zinc Sulfate ◽

Zinc Content ◽

Chelate Complex ◽

Molar Ratio ◽

X Ray ◽

Validation Parameters

Introduction. The production, standardization and quality control process of various dietary supplements containing chelated zinc requires validated quantitative assessment methods. In this work, we propose an X-ray fluorescence spectroscopy (XRF) technique for determining the zinc content in the composition of coordination compounds using the example of a synthesized chelate complex with methionine.Aim. To synthesize Zn(Met)2 chelate complex, to develop and validate a method for its quantitative analysis using the XRF method.Materials and methods. The synthesized zinc chelate complex was investigated by IR spectroscopy. The XRF method was used to develop a method for quantifying the zinc content in the synthesized complex. We used dry mixtures of zinc sulfate monohydrate and L-methionine (Met) in a molar ratio of Zn to Met – 1 : 1, 1 : 2, 1 : 4, 1 : 8 and 1 : 16 and also aqueous solutions of zinc sulfate and L-methionine in a molar ratio of Zn to Met 1 : 2 with Zn concentrations from 0.5 to 100 mmol/l as calibration standards. Complexometric titration was used as an arbitration method for the quantitative determination of zinc content in the samples under study.Results and discussion. The IR spectrum of chelate complex confirmed the presence of a donor-acceptor bond between Zn2+ and the nitrogen atom of amino group in methionine. The titration results showed chelate compounds have a composition corresponding to the stoichiometric formula Zn(Met)2. XRF analysis of dry standard mixed samples demonstrated the presence of matrix effect, that makes impossible an accurate assessment of zinc content in the chelate compound. According to the XRF spectra of aqueous solutions containing zinc sulfate and methionine in a ratio of 1 : 2 at a zinc concentration of 0.5; 1; 2; 3; 4; 5; 10; 25; 50 and 100 mmol/L, a calibration graph was constructed – the dependence of the fluorescence signal intensity for the Kα line of zinc on the concentration of zinc in the solution (r = 0.9996). The method was evaluated by the following validation parameters: specificity, linearity, correctness, precision, and analytical range. The specificity of the validated method was proven in the presence of copper, iron, and silver.Conclusion. The developed method make it possible to determine with sufficient precision and correctness the content of Zn2+ in its aqueous solutions of inorganic and organic nature by the XRF method in the concentration range from 3 to 100 mmol/l without the influence of the matrix.

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Adalimumab and anti-adalimumab LISA-TRACKER immunoassays performance criteria for therapeutic drug monitoring of adalimumab-amgen biosimilar (ABP501)

BMC Immunology ◽

10.1186/s12865-021-00473-1 ◽

2021 ◽

Vol 22 (1) ◽

Author(s):

Fabien Francois ◽

Loubna Naimi ◽

Xavier Roblin ◽

Anne-Emmanuelle Berger ◽

Stephane Paul

Keyword(s):

Human Serum ◽

Dynamic Range ◽

Polyclonal Antibodies ◽

Performance Criteria ◽

Clinical Samples ◽

Therapeutic Drug ◽

Serum Samples ◽

Acceptance Criteria ◽

Sample Stability ◽

Validation Parameters

Abstract Background ABP501 is a biosimilar to Reference Adalimumab (HUMIRA®) produced by AMGEN. Adalimumab (ADA) has a marketing authorization for Crohn's disease, ulcerative colitis and other inflammatory or autoimmune diseases. The aim of this study was to evaluate the LISA-TRACKER assays developed by Theradiag (France), for the monitoring of ABP501 and anti-ABP501 antibodies in human serum. Results 68 ABP501 clinical samples were measured with the LISA TRACKER Duo Adalimumab assay. LISA TRACKER has been validated as suitable for quantification of ABP501 in human serum samples. Accuracy of the LISA-TRACKER was measured using 3 human serum matrices spiked with known levels of biosimilar, 3 levels spanning the dynamic range. Percentages of recovery were ranged from 90 to 120% for biosimilar batch1, and between 93 and 105% for biosimilar batch2. The acceptance criteria (CV < 20%) were met for intra-run (from 3.8 to 16.5%) and inter-run imprecision (from 4.4 to 13.9%) including the two batches. All results were comprised within ± 20% from results, obtained with the kit and sample unexposed in order to evaluate stability of the sample, stability of the kit and consistency of the results. In any case, but two, all percentages of inhibition were > 50% for specificity. Specificity was tested with Biosimilar spiked samples, Biosimilar with Humira® spiked samples, and clinical samples from patients treated with adalimumab biosimilar. All of these samples were spiked with polyclonal antibodies directed against Humira®. Specificity inhibition and specificity detection steps were also part of the validation parameters. Reagents made with ABP501 gave similar results than reagents made with Humira® meeting acceptance criteria. Conclusions LISA-TRACKER ADA and anti-ADA assays are reliable for the monitoring of patients treated with ABP501.

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Studies on Radiopharmaceuticals

Nuklearmedizin ◽

10.1055/s-0038-1624802 ◽

1972 ◽

Vol 11 (04) ◽

pp. 407-418

Author(s):

Ken - ichi Tojyo ◽

Goro Urakubo ◽

Makoto Miki ◽

Toyohei Machida ◽

Takeshi Minami ◽

...

Keyword(s):

Activity Ratio ◽

Excretion Rate ◽

The Body ◽

Fecal Excretion ◽

Scintillation Camera ◽

Body Retention ◽

Male Wistar Rats ◽

Renal Scanning ◽

Excretion Rates ◽

First Time

SummaryAn attempt has been made to produce a new renal scanning agent with faster excretion rate, smaller radiation exposure and cheaper cost than those of chlormerodrin. A new compound l-(4-iodophenyl)-3-[3-(chloromercuri)-2-methoxypropyljurea (abbrev.: IPCM) labeled with 125I was prepared for the first time in four steps with 4-iodoaniline labeled with 125I as the starting material.The kidney affinity of the compound was examined by using male Wistar rats. The distribution of 125I in the organs at various intervals after administration was calculated using an organ/muscle activity ratio. The kidney accumulated more 125I than any other organ.The liver accumulated less 125I than the kidneys, but much more than any other organ. When the body retention of 203Hg-chlormerodrin and 203Hg- or l31I-IPCM was compared, similar biphasic excretion curves were found with both compounds.The urinary and fecal excretion rates of IPCM were nearly the same. Imaging of rabbit kidneys was also tried with a scintillation camera and 131I-IPCM. Some problems of the clinical application of IPCM are discussed with a view to the use of 123I in the future.

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Removal Pathway of Bioactive Glass Resorption Products from the Body

MRS Proceedings ◽

10.1557/proc-599-261 ◽

1999 ◽

Vol 599 ◽

Cited By ~ 3

Author(s):

W. Lai ◽

P. Ducheyne ◽

J. Garino ◽

C. M. Flaitz

Keyword(s):

Bioactive Glass ◽

Excretion Rate ◽

Atomic Absorption Spectrophotometry ◽

The Body ◽

The Other ◽

Soluble Form ◽

Control Group ◽

Flame Atomic Absorption ◽

Physiological Capacity

AbstractWe traced and quantified the silicon released from bioactive glass (BG) granules in vivo (45S5, 300–355 μm). 1500 mg of BG granules were implanted in the paraspinal muscle of 7 four kg rabbits. Blood samples and 24-hour urine samples were obtained over a 24 week period. Local muscle tissue as well as the following organs were harvested for chemical and histological analyses: brain, heart, kidney, liver, lung, lymph nodes, spleen, and thymus. Flame atomic absorption spectrophotometry was used to measure the concentration of elemental silicon in all the samples after digestion. Tissues and fluids from a sham group of 7 rabbits (underwent surgical procedure but received no implants) were obtained in a similar manner.The urinary silicon of the implanted group was significantly higher than in the control group. From the data, the calculated average excretion rate was approximately 2.4 mg/day, and as such, 100 percent of the implanted silicon was excreted in 19 weeks. No elevated concentrations of silicon were found at the implant site or in the other organs after 24 weeks. Histological appearance of all major organs was normal for all animals in the study.The concentrations of silicon measured in the urine were well below saturation and since no significant increase in silicon was found in the kidney or in the other organs, the increased silicon excretion rate was within the physiological capacity of rabbits. Therefore, it can be concluded that the resorbed silica gel is harmlessly excreted in soluble form through the urine.

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