scholarly journals Development and Validation of UPLC-MS / MS Method for Obtaining Favipiravir Tablet Dosage form and Evaluation of its Behavior Under forced Conditions

2021 ◽  
pp. 130-140
Author(s):  
Süleyman Gökce ◽  
Ayşen Höl ◽  
Ibrahim Bulduk
Keyword(s):  
Active Substance ◽  
Uv Light ◽  
Thermal Conditions ◽  
Test Method ◽  
Negative Ion ◽  
Ionization Source ◽  
Degradation Rates ◽  
Negative Ion Mode

Aims: Favipiravir (FVP) is a drug developed against RNA viruses. It is a drug that is used actively in the treatment of coronavirus. In vitro and in vivo investigations have shown that it inhibits the virus. In this study, a recovery study of tablet formulations was carried out by developing a UPLC-MS/MS method, which is used extensively in pandemic conditions. In addition, stability studies of favipiravir agent under forced conditions were conducted. The validated method is selective, robust, simple and applicable for tablet analysis. C18 (4.6 mm × 50 mm, 2.7 μm) column was used as the stationary phase and water-methanol (80-20 v/v) containing 0.1% formic acid was used as the mobile phase. UPLC optimization; It was conducted at a wavelength of 222 nm and a flow rate of 0.8 mL/min at 40 °C, retention time was 1.155 min. The electrospray jet stream ionization source was analyzed using mass spectrometry in negative ion mode. The molecular peak for Favipiravir was [M-1] 155.9, and the daughter ion determined 112.6. The stability test method was carried out in accordance with the ICH procedure. Reaction and degradation rates of the active substance under various forced conditions (acidic, basic, oxidative, UV light and thermal conditions) were investigated. The products formed by the decomposition of the active substance under stress conditions were determined by mass spectroscopy.

scholarly journals Fast Sensing of Hydrogen Cyanide (HCN) Vapors Using a Hand-Held Ion Mobility Spectrometer with Nonradioactive Ionization Source

Sensors ◽  
2021 ◽  
Vol 21 (15) ◽  
pp. 5045
Author(s):  
Victor Bocos-Bintintan ◽  
Ileana Andreea Ratiu
Keyword(s):  
Ion Mobility ◽  
Hydrogen Cyanide ◽  
Limit Of Detection ◽  
Chemical Warfare Agent ◽  
Source Model ◽  
Negative Ion ◽  
Industrial Chemicals ◽  
Ionization Source ◽  
Toxic Industrial Chemicals ◽  
Negative Ion Mode

Sensitive real-time detection of vapors produced by toxic industrial chemicals (TICs) always represents a stringent priority. Hydrogen cyanide (HCN) is definitely a TIC, being widely used in various industries and as an insecticide; it is a reactive, very flammable, and highly toxic compound that affects the central nervous system, cardiovascular system, eyes, nose, throat, and also has systemic effects. Moreover, HCN is considered a blood chemical warfare agent. This study was focused toward quick detection and quantification of HCN in air using time-of-flight ion mobility spectrometry (ToF IMS). Results obtained clearly indicate that IMS can rapidly detect HCN at sub-ppmv levels in air. Ion mobility spectrometric response was obtained in the negative ion mode and presented one single distinct product ion, at reduced ion mobility K0 of 2.38 cm2 V−1 s−1. Our study demonstrated that by using a miniaturized commercial IMS system with nonradioactive ionization source model LCD-3.2E (Smiths Detection Ltd., London, UK), one can easily measure HCN at concentrations of 0.1 ppmv (0.11 mg m−3) in negative ion mode, which is far below the OSHA PEL-TWA value of 10 ppmv. Measurement range was from 0.1 to 10 ppmv and the estimated limit of detection LoD was ca. 20 ppbv (0.02 mg m−3).

Comprehensive and Rapid Identification of Astilbin Metabolites in Rats Based on Multiple Metabolite Templates Combined with UHPLC-Q-ExactiveMass Spectrometry

2021 ◽  
Vol 22 ◽  
Author(s):  
Shan Jiang ◽  
Haoran Li ◽  
Ailin Yang ◽  
Hongbing Zhang ◽  
Pingping Dong ◽  
...  
Keyword(s):  
Mass Spectrometer ◽  
Biological Effects ◽  
Rat Plasma ◽  
Rapid Identification ◽  
Negative Ion ◽  
Ring Cleavage ◽  
Rat Urine ◽  
Q Exactive ◽  
Negative Ion Mode

Background : Astilbin, a dihydroflavonoid compound widely found in plants, exhibits a variety of pharmacological activities and biological effects. However, little is known about the metabolism of this active compound in vivo, which is very helpful for elucidating the pharmacodynamic material basis and application of astilbin. Objective: To establish a rapid profiling and identification method for metabolites in rat urine, faeces and plasma using a UHPLC-Q-Exactive mass spectrometer in negative ion mode. Methods: In this study, a simple and rapid systematic strategy and 7 metabolite templates, which were established based on previous reports, were utilized to screen and identify astilbin metabolites. Results: As a result, a total of 72 metabolites were detected and characterized, among which 33 metabolites were found in rat urine, while 28 and 38 metabolites were characterized from rat plasma and faeces, respectively. These metabolites were presumed to be generated through ring cleavage, sulfation, dehydrogenation, methylation, hydroxylation, glucuronidation, dehydroxylation and their composite reactions. Conclusion: This study illustrated the capacity of the sensitive UHPLC-Q-Exactive mass spectrometer analytical system combined with the data-mining methods to rapidly elucidate the unknown metabolism. Moreover, the comprehensive metabolism study of astilbin provided an overall metabolic profile, which will be of great help in predicting the in vivo pharmacokinetic profiles and understanding the action mechanism of this active ingredient.

Optimization of zinc oxide nanoparticle-catalyzed in vitro bilirubin photolysis and in vivo treatment of hyperbilirubinemia

Nanomedicine ◽  
2021 ◽  
Author(s):  
Haq Nawaz ◽  
Iqra Naseem ◽  
Tanzila Rehman ◽  
Mubashir Nawaz
Keyword(s):  
Zinc Oxide ◽  
Zinc Oxide Nanoparticles ◽  
Uv Light ◽  
Uv Exposure ◽  
Uv Treatment ◽  
Blood Samples ◽  
Positive Effects ◽  
Oxide Nanoparticle

Aim: To optimize the Zinc oxide nanoparticles (ZnONPs)-catalyzed in vitro photolysis of bilirubin and to test their effect on bilirubin clearance in vivo. Materials & methods: ZnONPs, synthesized in an alkaline medium, were characterized. Response surface methodology was used to optimize the in vitro photolysis catalyzed by the nanoparticles (NPs). Blood samples from phenylhydrazine-induced hyperbilirubinemic rabbits which had been administered ZnONPs and UV light were analyzed to assess in vivo clearance of bilirubin. Results: The ZnONP-assisted UV treatment showed the linear and quadratic positive effects on the in vitro bilirubin photolysis with an optimal photolysis of bilirubin at 225 mg dl-1 concentration of ZnONPs and a UV exposure of 1.80 h. The ZnONP-assisted phototherapy of hyperbilirubinemic animals was also found to be more effective for in vivo clearance of bilirubin than phototherapy alone. Conclusion: After further trials, ZnONP-assisted phototherapy could be a potential treatment for hyperbilirubinemia in humans.

scholarly journals Skrining Mekanisme Kerja Daun Malaka (Phyllanthus emblica L.) Sebagai Antidiabetes

2018 ◽  
Vol 1 (3) ◽  
pp. 106-110
Author(s):  
Novi Irwan Fauzi ◽  
Seno Aulia Ardiansyah ◽  
Saeful Hidayat
Keyword(s):  
Mechanism Of Action ◽  
Inhibitory Activity ◽  
Leaf Extract ◽  
Test Method ◽  
Diabetic Rat ◽  
Phyllanthus Emblica ◽  
Insulin Sensitizer ◽  
Water Fraction

Daun malaka (Phyllanthus emblica L.) mempunyai potensi digunakan sebagai alternatif obat antidiabetes. Daun malaka menunjukkan efek hipoglikemia pada tikus yang diinduksi aloksan. Namun, mekanisme kerjanya belum diketahui pasti. Penelitian ini dilakukan dalam rangka skrining mekanisme kerja daun malaka sebagai antidiabetes. Skrining mekanisme kerja dilakukan terhadap fraksi air daun malaka melalui uji aktivitas inhibisi enzim α-glukosidase serta α-amilase secara in vitro dan pengujian aktivitas insulin-sensitizer terhadap ekstrak daun malaka dengan metode tes toleransi insulin secara in vivo. Fraksi air daun malaka menunjukkan aktivitas inhibisi terhadap enzim α-glukosidase serta α-amilase dengan nilai IC50 (Inhibitor Concentration 50) pada kedua enzim tersebut berturut-turut adalah 0,87% dan 8,64% b/v. Pada uji aktivitas insulin sensitizer, pemberian ekstrak daun malaka dapat meningkatkan sensitivitas insulin pada tikus diabet dengan kondisi resistensi insulin. Nilai KTTI pada kelompok tikus diabet yang diberi ekstrak daun malaka dosis 100 dan 500 mg/kgbb tikus (74,89 dan 75,57) lebih tinggi dibandingkan kelompok tikus diabet (38,41) dan kadar glukosa darah yang lebih rendah selama interval waktu pengukuran. Daun malaka telah diketahui mampu meningkatkan sekresi insulin dan pada penelitian ini menunjukkan aktivitas inhibisi enzim α-glukosidase serta α-amilase secara in vitro dan menunjukkan aktivitas insulinsensitizer pada tikus diabet dengan kondisi resistensi insulin.   Malaka leaf (Phyllanthus emblica L.) has the potential to be used as an alternative antidiabetic drug. Malacca leaves showed hypoglycemia effect in rat induced by alloxan. However, the mechanism of action is not yet known. This study was conducted to evaluate the mechanism of action of Malaka leaves as antidiabetic. Screening of the mechanism of action was carried out on the water fraction of Malaka leaf  byinhibitory activity examination  on α-glucosidase and α-amylase by in vitro studyand Evaluation of insulin-sensitizer activity of Maaka leaf leaf extract was conducted by invivo  insulin tolerance test method. Malaka leaf water fraction showed inhibitory activity against the α-glucosidase and α-amylase with IC50 values ​​(Inhibitory Concentration 50)  of0.87% and 8.64% b / v on both enzyme, respectively. The evaluation of insulin sensitizer revelead that administration ofMalaka  leaf extract can increase insulin sensitivity in diabetic rat with insulin resistance.KTTI values ​​in diabetic rats given malaka extract  at the dose of 100 and 500 mg / kg BW (74.89 and 75.57) were higher than diabetics rat (38.41) and the extract also decrease blood glucose levels during measurement time intervals . Malaka leafhas been known to increase insulin secretion and the study showedthe  inhibitory activity on α-glucosidase and α-amylase by in vitro study and showed insulinsensitizer activity in diabetic rat with insulin resistance.

Pharmacokinetics, Tissue Distribution, and Excretion Study of Cajanonic Acid A in Rats by UPLC-MS/MS

Planta Medica ◽  
2020 ◽  
Vol 86 (05) ◽  
pp. 312-318
Author(s):  
Li Zhang ◽  
Rui Chen ◽  
Yujuan Ban ◽  
Jin Cai ◽  
Jingang Peng ◽  
...  
Keyword(s):  
Tyrosine Phosphatase ◽  
Pigeon Pea ◽  
Negative Ion ◽  
Biological Behavior ◽  
Peroxisome Proliferator ◽  
Potential Candidate ◽  
Peroxisome Proliferator Activated Receptor ◽  
Single Reaction Monitoring ◽  
Negative Ion Mode

AbstractCajanonic acid A (CAA), a prenylated stilbene derivative extracted from the leaves of pigeon pea (Cajanus cajan), has been reported to possess inhibitory activity on the peroxisome proliferator-activated receptor gamma (PPARγ) and protein tyrosine phosphatase 1B (PTP1B). Its hypoglycemic activity in rats is comparable to that of the approved antidiabetic agent rosiglitazone. Therefore, CAA is a potential candidate for the treatment of type 2 diabetes and a lead compound for the discovery of novel hypoglycemic drugs. To achieve a thorough understanding of the biological behavior of CAA in vivo, our current study was designed to investigate the pharmacokinetics, bioavailability, distribution, and excretion of CAA in rats by UPLC-MS/MS. Chromatographic separation was performed on BEHC18 column (2.1 mm × 50 mm, 1.7 µm). Quantification was performed under the negative ion mode by using single reaction monitoring (SRM) of the transitions of m/z 353.14 → 309.11 for CAA and m/z 269.86 → 224.11 for genistein, respectively. Standard calibration curve showed excellent linearity (r2 > 0.99) within the range of 2 – 800 ng/mL. The accuracies and precisions were within the acceptance limits (all < 20%). CAA was quickly absorbed into bloodstream and distributed rapidly and widely to various tissues. The excretion ratio of CAA in the 3 main pathways via bile, feces, and urine was only 5.17%. These results indicate that CAA was quickly and thoroughly metabolized in vivo and excreted mainly as metabolites.

scholarly journals Microstructure and Mechanical Properties of PU/PLDL Sponges Intended for Grafting Injured Spinal Cord

Polymers ◽  
2020 ◽  
Vol 12 (11) ◽  
pp. 2693
Author(s):  
Anna Lis-Bartos ◽  
Dariusz Szarek ◽  
Małgorzata Krok-Borkowicz ◽  
Krzysztof Marycz ◽  
Włodzimierz Jarmundowicz ◽  
...  
Keyword(s):  
Mechanical Properties ◽  
Spinal Cord ◽  
Young Modulus ◽  
In Vivo Studies ◽  
Polymer Composition ◽  
In Vitro Toxicity ◽  
Injured Spinal Cord ◽  
Degradation Rates

Highly porous, elastic, and degradable polyurethane and polyurethane/polylactide (PU/PLDL) sponges, in various shapes and sizes, with open interconnected pores, and porosity up to 90% have been manufactured. They have been intended for gap filling in the injured spinal cord. The porosity of the sponges depended on the content of polylactide, i.e., it decreased with the increase of polylactide content. The rise of polylactide content caused an increase of Young modulus and rigidity as well as a more complex morphology of the polyurethane/polylactide blends. The mechanical properties, in vitro toxicity, and degradation in artificial cerebrospinal fluid were tested. Sponges underwent continuous degradation with varying degradation rates depending on the polymer composition. In vitro cell studies with fibroblast cultures proved the biocompatibility of the polymers. Based on the obtained results, the designed PU/PLDL sponges appeared to be promising candidates for bridging gaps within injured spinal cord in further in vitro and in vivo studies.

Natural Poly(Hydroxybutyrate-Hydroxyvalerate) Polymers as Degradable Biomatertals.

1995 ◽  
Vol 394 ◽  
Author(s):  
Cyril Chaput ◽  
L'Hocine Yahia ◽  
Amine Selmani ◽  
Charles-Hilaire Rivard
Keyword(s):  
Copolymer Composition ◽  
Inflammatory Reactions ◽  
Accelerated Degradation ◽  
Physico Chemical ◽  
Degradation Rates ◽  
Degradable Biomaterials ◽  
Tissue Reactions ◽  
Toxic Responses

AbstractPoly(ß-hydroxybutyrate-co-13-hydroxyvalerate) have been recently proposed as degradable biomaterials for drug delivery systems, sutures, bone plates and short-term implants. Three P-B\HV (7, 14 & 22 % HV) films were analyzed for in vitro cytotoxicity and aqueous accelerated degradation, in vivo degradation and tissue reactions. The PHB/HV materials and extracts elicit few or mild toxic responses, do not lead in vivo to tissue necrosis or abscess formation, but provoke acute inflammatory reactions slightly decreasing with the time. The degradation of PHB/HV polymers present low rates in vitro as well as in vivo. The weight loss rate generally increases with the copolymer composition (HV content) and ranges from 0.15- 0.30 (in vitro) to 0.25 %/day (in vivo). Compositional and physico-chemical changes in PHB/HV materials were rapidly detected during the accelerated hydrolysis, but were much slower to appear in vivo. The structural and mechanical integrity of PHB/HV materials tend to disappear early in vitro as well as in vivo. After 90 wks in dorsal muscular tissues of adult sheep, there was no significant dissolution of the PHB/HV polymer, 50–60% of the initial weight still remaining. PHB/HV polymers are biodegradable materials, either by hydrolysis or implantation, but with extremely low dissolution or degradation rates.

136 IN VITRO DEVELOPMENT OF BOVINE EMBRYOS SUBMITTED TO LASER ASSISTED HATCHING ON DAY 6 AND DAY 7 OF EMBRYO CULTURE

2009 ◽  
Vol 21 (1) ◽  
pp. 168
Author(s):  
C. B. Ponchirolli-Schneider ◽  
J. H. Pryor ◽  
C. R. Looney
Keyword(s):  
Embryo Culture ◽  
Uv Light ◽  
Laser System ◽  
Pulse Length ◽  
Assisted Hatching ◽  
In Vitro Production ◽  
Stage Of Development ◽  
Number Of Cells

In vitro production (IVP) of embryos is a valuable tool in bovine assisted reproduction. IVP embryos show lower pregnancy rates when compared to in vivo produced embryos. The inability of the IVP embryo to hatch from the zona pellucida (ZP) after embryo transfer is believed to be one contributing factor. The aim of this study was to compare the ability of IVP embryos to hatch and develop in vitro after being submitted to laser assisted hatching (LAH) at two different time periods of embryo culture: 144 h (Day 6) and 168 h (Day 7). In vitro maturated oocytes from slaughterhouse ovaries (Ovitra Biotechnologies, Amarillo, TX, USA) were fertilized with frozen/thawed semen from two different bulls (Day 0) and cultured in G1.5/G2.5 medium supplemented with 8 mg mL–1 of BSA (Vitrolife, Englewood, CA, USA) at 38.5°C, 5% CO2, 5% O2, 5% N2, in humidified atmosphere. On Day 6 post-fertilization, all viable embryos (n = 251), from three replicates, were washed in holding medium (Vigro Holding Plus, Bioniche, Pullman, WA, USA) and divided into four treatment groups: laser assisted hatching Day 6 and Day 7 (LAHD6 and LAHD7), control Day 6 and Day 7 (CD6 and CD7). The groups LAHD7 and CD7 were immediately placed in G2.5 and returned to the incubator until Day 7. Embryos from groups LAHD6 and CD6 were placed in G2.5 in separate wells of a four well dish and covered with 300 μL of mineral oil. Embryos from LAHD6 group had one third to one half of the external edge of the ZP exposed to a laser beam, using XY Clone® (Hamilton Thorne Biosciences, Inc., Beverly, MA, USA) laser system, with a pulse strength of 90% and a pulse length of 600 μs. The group CD6 was submitted to the same conditions, but did not receive the laser treatment. On Day 7, the experiment was repeated for embryos belonging to groups LAHD7 and CD7. Embryos from all groups were cultured in vitro and evaluated on Day 8 and Day 9 for stage of development. On Day 9, a random sample of embryos from each treatment group (n = 48) was stained with Hoechst 33342 (2.5 μg mL–1) and evaluated under UV light to determine the total number of cells. The number of hatched blastocysts was not different (chi-square, p > 0.05) among the groups on Day 9 of culture (LAHD6 = 49/66, CD6 = 38/61, LAHD7 = 42/59, CD7 = 47/65; 74, 62, 71 and 72%, respectively). However, on Day 8 of culture, LAHD6 showed a higher number (p < 0.05) of hatched blastocysts (40/66, 60%), when compared to group CD6 (26/61, 42%). There was no difference between groups LAHD7 (33/59, 55%) and CD7 (31/65, 47%) on Day 8. Comparison of the total number of cells showed no difference (Student’s t-test, p > 0.05) among the groups (LAHD6 = 154.8 ± 12.2, CD6 = 184.4 ± 19.5, LAHD7 = 170.4 ± 15.8, CD7 = 162.5 ± 14.6), indicating that LAH does not have a detrimental effect on mean cell production throughout embryo development in vitro. These data show that LAH on Day 6 of culture improves in vitro hatching rates on Day 8, while LAH on Day 7 shows no improvement on either Day 8 or 9. Kathy Bradley, Hamilton Thorne Biosciences, Inc.

A Critical Review of the Durability of Adhesion to Tooth Tissue: Methods and Results

2005 ◽  
Vol 84 (2) ◽  
pp. 118-132 ◽  
Author(s):  
J. De Munck ◽  
K. Van Landuyt ◽  
M. Peumans ◽  
A. Poitevin ◽  
P. Lambrechts ◽  
...  
Keyword(s):  
Gold Standard ◽  
Test Method ◽  
Chemical Degradation ◽  
Morphological Evidence ◽  
Aging Effects ◽  
Application Procedure ◽  
Etch And Rinse ◽  
Clinical Benefits

The immediate bonding effectiveness of contemporary adhesives is quite favorable, regardless of the approach used. In the long term, the bonding effectiveness of some adhesives drops dramatically, whereas the bond strengths of other adhesives are more stable. This review examines the fundamental processes that cause the adhesion of biomaterials to enamel and dentin to degrade with time. Non-carious class V clinical trials remain the ultimate test method for the assessment of bonding effectiveness, but in addition to being high-cost, they are time- and labor-consuming, and they provide little information on the true cause of clinical failure. Therefore, several laboratory protocols were developed to predict bond durability. This paper critically appraises methodologies that focus on chemical degradation patterns of hydrolysis and elution of interface components, as well as mechanically oriented test set-ups, such as fatigue and fracture toughness measurements. A correlation of in vitro and in vivo data revealed that, currently, the most validated method to assess adhesion durability involves aging of micro-specimens of biomaterials bonded to either enamel or dentin. After about 3 months, all classes of adhesives exhibited mechanical and morphological evidence of degradation that resembles in vivo aging effects. A comparison of contemporary adhesives revealed that the three-step etch-and-rinse adhesives remain the ‘gold standard’ in terms of durability. Any kind of simplification in the clinical application procedure results in loss of bonding effectiveness. Only the two-step self-etch adhesives approach the gold standard and do have some additional clinical benefits.

Unexpected cytosine–AuCl4− interaction under electrospray ionization mass spectrometry conditions—Formation of cytosine–Au(I) complexes

2019 ◽  
Vol 26 (3) ◽  
pp. 225-229
Author(s):  
Magdalena Frańska ◽  
Emilia Konował
Keyword(s):  
Electrospray Ionization ◽  
Gas Phase ◽  
Mass Spectra ◽  
Mass Spectrometric ◽  
Negative Ion ◽  
Ionization Mass ◽  
Ionization Source ◽  
Full Scan ◽  
Negative Ion Mode ◽  
Product Ion Spectra

The interaction of cytosine with AuCl4−, under electrospray ionization mass spectrometric conditions, is discussed. On the basis of respective full scan mass spectra and product ion spectra, obtained in positive and negative ion mode, it has been deduced that cytosine is very prone to form Au(I)-containing complexes. The complexes may be formed in the gas phase by decomposition of Au(III)-containing complexes and also in the electrospray ionization source as a result of the occurrence of redox process. It has also been found that the interaction of cytosine with Au+ is stronger than that with Cu+ or Ag+, although taking into account the electrostatic attraction, it is not expected.

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