International Journal of Current Research and Review
ISSN: 2231-2196 (Print)ISSN: 0975-5241 (Online)
logo
slider
slider
slider
slider
Bootstrap Slider

Indexed and Abstracted in: Crossref, CAS Abstracts, Publons, Google Scholar, Open J-Gate, ROAD, Indian Citation Index (ICI), ResearchGATE, Ulrich's Periodicals Directory, WorldCat (World's largest network of library content and services)

Search Articles

Track manuscript

Full Html

IJCRR - 14(1), January, 2022

Pages: 33-39

Date of Publication: 03-Jan-2022


Print Article   Download XML  Download PDF

Liquid Chromatography - Mass Spectrometry Method Development and its Validation for the Estimation of Favipiravir and Remdesivir in the Rat Plasma

Author: K. Santhakumari, K. Prasada Rao, S. Mohan

Category: Healthcare

Abstract:Introduction: Liquid Chromatography Mass Spectrometry (LC-MS/MS) is an exceedingly sensitive and specific analytical technique that can precisely determine the identities and concentration of compounds within our sample. Objective: A selective, sensitive, and rapid bio-analytical technique has been developed and it is validated by using Liquid chromatography \? Mass spectrometry (LC-MS/MS) process for the estimation of favipiravir and remdesivir in rat plasma Methods: An isocratic mode using the analytical column of waters symmetry C18 150 mm x 4.6 mm, 3.5 µm, and the mobile phase acetonitrile and buffer in the ratio of 30+70. The method was validated with a linearity range 2-40 ng/mL of both favipiravir and remdesivir. The % CV values of intraday, interlay precision and accuracy were found to be within the acceptance criteria. The % recovery of favipiravir was 96.5% and remdesivir was 99.6% respectively Results: The validation of the method has been done successfully in parameters like accuracy, linearity, recovery, stability and pharmacokinetic studies in rat plasma using LCMS/MS. Stability of the selected drugs present in all conditions like benchtop, wet extract, auto sampler stability, and freeze thaw. Conclusion: This technique gives better results of precision, accuracy, recovery, precision, pharmacokinetic studies, and stability in the rat plasma. The proposed technique was validated as per the guidelines set by International Conference on Harmonization (ICH).

Keywords: Favipiravir, HPLC, LC-MS, Remdesivir, Validation, Stability

Full Text:

INTRODUCTION

Gilead Sciences has developed Remdesivir as an antiviral drug by the name GS-5734.1 This drug requires bioactivation within the cells.2 Remdesivir contain various basic molecular characteristics, this is an analogue of adenosine nucleotide, it comprises the RNA synthesis and as a result, it acts against RNA viruses.

The validation method of UHPLC-MS/MS of remdesivir and its GS-441524 quantification has been reported in human plasma in the literature. The evaluation of analyte stability has been done in detail.3 This method has been successfully validated and it states that the sample thermal inactivation is the best choice to improve biosafety.

For treating Nipah virus in African green monkey model the remdesivir shows a practicable and which is having great effect.4, 5 This model explained by performing the experiments by infection with a fatal dose of the virus to the animals which are selected for this purpose with one dose of remdesivir daily for 12 days. The results showed that all the treated animals are saved compared to the untreated animals.

This drug is potent which inhibits selectively influenza viral RNA polymerase,6 also active against various strains and subtypes of viruses of influenza all subtypes and strains of influenza viruses including the ones sensitive to marketed M2 inhibitors and neuraminidase.

Favipiravir, initially used for treating against the SARS-CoV-2 in Wuhan,  and as the virus spread to European countries, it has received emergency approval for use this drug received approval for emergency use in some other countries and it received DCGI approval for various levels of  Covid-19 infections. There are various clinical trials going on to assess the drug’s efficiency in managing the Covid-19 .7

Favipiravir (T-705) has been discovered initially during the assessment of chemical agents for their antiviral activity and it is effective in treating the influenza virus and reported in the chemical library of Toyoma chemicals. Favipiravir has been obtained with various modifications done on pyrazine moiety of T-1105 chemically.8, 9 Favipiravir exhibits useful anti-viral activities with other RNA viruses’ also.10

The literature review suggests that a few methods for evaluating Favipiravir and Remdesivir had been published. However, have developed a method for the validation of these drugs in rat plasma by using LCMS/MS has been carried out in this paper. The newly developed process has been effectively validated using the guidelines set by International Conference on Harmonization (ICH).11,12,13

MATERIALS AND METHODS

Instrumentation

Chromatography has been carried out with waters 2695 HPLC containing degasser, column oven, high-speed autosampler, and SCIEX QTRAP 5500 mass spectrometer for providing a compact and with class Empower-2 software.

Reagents and chemicals

The reference sample was provided as Favipiravir and Remdesivir samples from Biocon, Bangalore. The chemicals like acetonitrile, and methanol used are of HPLC grade and procured from Merck chemical supplier, Mumbai. Throughout the process the water used of HPLC grade which is obtained from Milli-Q water purification system.

Favipiravir Standard Stock Solution (80 ng/mL)

Weigh 8 mg of Favipiravir and diluted with a diluents in a 100 mL volumetric flask. Further dilute 0.1 mL to 100 mL with diluent.

Remdesivir Standard Stock Solution (80ng/mL)

Weigh 8 mg of Remdesivir standard in a 100 mL flask and diluted it with a diluent. Further dilute 0.1ml of above solution in 100 mL volumetric flask with diluent.

Preparation of Standard Solutions (20 ng/mL of Favipiravir and 20 ng/mL of Remdesivir)

In a centrifuged tube 500 µl of Favipiravir and Remdesivir standard stock solutions are taken. Dilute to volume with Plasma, acetonitrile and diluent.   

Preparation of Linearity solution         

These solutions are prepared with concentrations from 2 nanogram to 40 nanogram per mL of Favipiravir and Remdesivir prepared in a similar way as above. Centrifuge at 4000 RPM for 15 – 20 min. collect the supernatant solution in LC vial and inject into the chromatograph.

Extraction procedure

The treated and centrifuged plasma samples are labelled as per the time intervals. 200 μL sample of plasma is added with 500 μL diluent and shaken it well. Further add 300 μL of Acetonitrile for precipitation of proteins and thoroughly mix it in a vortex cyclo mixture. It is centrifuged at about 4000 RPM for about 15 – 20 min, and the supernatant solution is collected in a HPLC vial and injected into a chromatograph.

Buffer Preparation

Transfer 1ml of formic acid into a1lt water. Filter by using 0.45µ membrane paper.

Methodology for Analysis

The Linearity solution, the blank, and sample solutions are injected into the chromatograph and their chromatograms have been recorded. The peak areas due to Favipiravir and Remdesivir are measured. The linearity curve obtained from the equation express the concentration of these compounds present in the sample of plasma.

RESULTS AND DISCUSSIONS

System suitability

The instrument efficiency is determined by performing analysis with a set of standard and reference ones prior to the analytical process. The percentage of cumulative variation (% CV) for Favipiravir and Remdesivir was found to be 0.31 and 0.29 and area ratio of ISTD has been observed to be 0.59 %, and 0.44 %. Therefore, the suitability of the system has passed.

Specificity and screening of biological matrix

It was observed that in the samples blank rat plasma there were no interfering peaks of Favipiravir and Remdesivir or ISTD at retention times. The interfering peaks response in the standard (STD) Blank at the analyte retention time should be ≤ 20.00 % of that in LLOQ (Lower limit of quantification). Response of peaks that interfere at retention time in the STD Blank and the ISTD should be ≤ 5.00 % of that in LLOQ. About 80 % of the lots of the matrix (except heparinized, haemolysed and lipemic matrix lots) must be in the acceptance criteria with intended anticoagulant.

 Sensitivity                                                                                                    

The % CV for Favipiravir and Remdesivir was found to be 1.16 % and 0.71 %. % CV accuracy was 99.3 % and 99.4 %. Hence the sensitivity was passed.

Matrix effect

The matrix effect was determined for rat plasma constituents over ionization of the analyte and compared the post-extracted plasma standard MQC (Medium quality control) samples' response (20 ng/ml of Favipiravir and 20 ng/ml of Remdesivir) (n = 6) with that of the analyte from pure samples at the equivalent concentrations. The intended method of the matrix effect has been assessed with chromatographically screened plasma of the rat.

Precision (% CV) for Favipiravir was found to be 0.39 % and 0.77 % for respectively at HQC (High-quality control) and LQC (Low-quality control). Precision (% CV) for Remdesivir was found to be 0.36% and 0.69 % respectively at HQC and LQC. The percentage mean accuracy of the back-calculated concentrations of LQC, and HQC samples that are prepared with lots of different biological matrix must be within the 85.00-115.00 %. This shows that matrix effect on ionization of the analyte has been shown to be in the limit of acceptance. Figure 1 shows the Matrix Effect Chromatogram of LQC.

Linearity

Over concentration range of2-40 ng/mL the standard curves was linear for Favipiravir and Remdesivir. The correlation coefficient has been found to be 0.992 for Remdesivir and it is 0.9901 for Favipiravir. The calibration curves are found to be linear.  By using ratio of peak area of the analyte and that of IS the samples have been quantified. The ratios of the peak area are plotted against concentrations of the plasma. The calibration standards’ peak area ratios were found to be proportional to the concentrations. Linearity results of Favipiravir were shown in table 1 and for Remdesivir were shown in Table 2. Figures 2, and 3 shows the plot of calibration for the concentration vs Area ratio of Favipiravir and Remdesivir respectively.

LOD and LOQ

Table 3 shows the LOD and LOQ results of the compounds. Limit of detection (LOD) and limit of quantification (LOQ) have been determined separately with a method of calibration curve. The compound’s LOD and LOQ have been calculated by progressive injection of standard solutions of lower concentrations with the developed LC-MS method. The concentration of LOD for Favipiravir is 0.2 ng/ml and the S/B value is 7. The concentration of LOQ for Favipiravir is 2.2ng/ml and the S/B value is 27. The LOD concentrations for Remdesivir are 0.2 ng/ml the S/B value is 5. The LOQ concentration for Remdesivir is 2.2 ng/ml the S/B value is 22. The chromatograms for MQC and blank are shown in figures 4 and 5 respectively.

Precision and accuracy

The estimation of precision and accuracy has done by analysis of six replicates with Favipiravir and Remdesivir at four kinds of QC levels. The determination of the inter-assay precision was done by the analysis of four levels QC samples with four different runs. For accepting the data the criteria include, the accuracy in the range 85–115% from actual value and the precision in the range of ±15% RSD except for LLQC, where it should be in the range of 80–120% r accuracy and <20% RSD.

Recovery of analyte

The IS and the drug recovery has been carried out at three levels of concentrations like high, medium and low quality control. By comparing the response in the replicate samples with the responses of neat standard solutions the recovery is determined. The recovery of the analyte from sample matrix is (extraction efficiency) done by comparing the response of the analyte from the amount of added analyte with that calculated from the sample matrix. Because of the basic properties of Favipiravir and Remdesivir, the extraction was done with Acetonitrile solvent.

The results of the recoveries of the analyte with the experiments with the spiked compounds are 85.1 % - 90.5 % and for IS 84.25 %. At each QC level % CV of recovery and for ISTD should be ≤ 15.00 %. Overall mean recovery of % CV for all QC levels should be ≤ 20.00 %. Recovery plots for Favipiravir and Remdesivir in Rat plasma were shown in figures 6 and 7 respectively.

Ruggedness on precision accuracy

The % CV for Favipiravir and Remdesivir was found to be 0.07-1.27 %. The LLOQ QC should be in the range of 80.00-120.00 %. The % mean accuracy of LQC, MQC and HQC samples should be in the range of 85.00-115.00 %, and in case of samples of LLOQ QC, it should be in the range of 80.00-120.00 %. Hence the Ruggedness on precision accuracy was passed.

Ruggedness on reinjection reproducibility

The %CV for Favipiravir and Remdesivir were found to be 0.12 %-1.89 %. The % mean accuracy of samples of LQC, MQC, and HQC should be in the range of 85.00-115.00 % and in case of samples of LLOQ QC it should be in the range of 80.00-120.00 %. Hence the Ruggedness on reinjection reproducibility was passed.

Bench Top Stability

The % CV of HQC and LQC, mean accuracy for Favipiravir and Remdesivir were found to be 0.09% and 0.38%, 98.2 %, 98.6 % and 0.08 %, 0.31 %, 98.8 %, 98.5 %. Hence the Bench top stability was passed.

Auto Sampler Stability

The % CV of the HQC, MQC, LQC, and the mean accuracy for Favipiravir were found to be 0.06%, 98.3 %, 0.62 %, 98.2 %, 1.80 %, and 98.5 % and for Remdesivir were found to be 0.60%, 98.8%, 0.62 %, 98.6 %, 1.22%, 98.4 %. Hence the Auto Sampler Stability was passed.

Freeze Thaw

The % CV and the mean accuracy for Favipiravir was observed to be 0.08 %, 98.2 % and 0.28%, 98.6% and for Remdesivir was found to be 0.11 %, 98.8 % and 0.17 %, 98.5 %. The % mean stability for LQC and HQC samples should be in the range of 85.00-115.00 %. Hence the freeze thaw stability was passed.

Wet Extract

The % CV and the mean accuracy of Favipiravir was found to be 0.10 %, 98.2 % and 0.24 %, 98.6 % and for Remdesivir was 0.08 %, 99.8% and 0.17 %, 99.5 %. The % mean stability of samples of LQC and HQC should be in the range of 85.00-115.00 %. Hence the stability of the wet extract was passed.

Dry Extract

The % mean accuracy of the back-calculated concentration of samples of LQC and HQC should be in the range of 85.00-115.00 %. The % CV of samples of LQC and HQC should be ≤ 15.00 %. The % mean stability of samples of LQC and HQC should be in the range of 85.00-115.00 %.

The % CV and mean accuracy in different intervals of time for Favipiravir and for Remdesivir were passed. It indicates the Dry Extract stability.

Short term

Short term stability of Favipiravir and Remdesivir were shown in Table 4 and Table 5. The % CV of samples of HQC, LQC and MQC samples for Favipiravir was 0.66, 4.18 and 1.04 and for Remdesivir was 0.09, 0.26 and 0.13. Mean accuracy for Favipiravir was 95.99 %, 95.88 % and 96.98 % and for Remdesivir was 81.52 %, 88.78 % and 85.76 %. The short term stability was passed.

Pharmacokinetic Studies

Table 6 shows the Pharmacokinetic studies of the compounds. For isolation of Favipiravir and Remdesivir from rat plasma liquid-liquid extraction technique has been used.  To carry out this, plasma sample (200µl) (respective concentration) was added into labeled polypropylene tubes and swirl briefly and add 0.3 ml of Acetonitrile and vortexed for 10 min and centrifuge this at 20 °C at 4000 rpm. The supernatant liquid from these samples was taken into a label vial tube and evaporate the solvent to dry at 40 °C. The samples have been reconstituted with a 500 µl of diluent and briefly vortexed and transferred for injection into a autosampler vials.

The sample of Favipiravir and Remdesivir was injected into the rat body and samples collected at various time intervals like 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4 and 5 h in six different rats. After that samples are prepared as per test method and injected into a chromatographic system and recorded values. At 2 h Favipiravir and at 1 h Remdesivir reaches the maximum result.

The study of pharmacokinetics of Favipiravir and Remdesivir has been carried out in healthy South Indian male subjects (n = 6). The written informed consent was taken from all the volunteers and the protocol has been approved by the local Independent Ethics Committee. The single dose of Favipiravir tablet (200 mg) and Remdesivir injection (100 mg) was given orally to the volunteers and collected the samples of blood at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4 and 5 h post-dose. An aliquot of 5 mL blood was collected at each point of time in a K2 EDTA vacutainer tubes. Additionally, in order to check the possible interferences from plasma the predose sample was collected. To obtain the plasma the samples were collected, centrifuged, and stored at −70}10 °C. The samples of plasma were spiked with IS and it is processed at four concentrations along with QC samples. The parameters of pharmacokinetics of Favipiravir and Remdesivir have been calculated with WinNonlin (Version 5.2) software. The stability of these samples was established using incurred sample reanalysis (ISR). For this ISR purpose two samples from each subject were selected (10 samples in total) near the Cmax and elimination phase in pharmacokinetic profile. These samples were considered stable and the % difference should not be higher than20.

CONCLUSION

The main objective of the work presented here is to develop a simple, sensitive, cost-effective, and rugged method for determining Favipiravir and Remdesivir in LC-MS with internal standards Favipiravir-D6 and Remdesivir-D6. The proposed work suggests less run time in comparison with other work articles. The total run time in chromatographic studies is 8.0 min and with a retention time for Favipiravir and Remdesivir respectively at 2.241, and 5.098 min. This method has been validated for Favipiravir and Remdesivir over a dynamic linear range of 2-40 ng/mL and with correlation coefficient of r2 0.999.  The intra-batch and inter-batch precision (% CV) across five levels (LLOQ, ULOQ, LQC, MQC, and HQC) is less than 11.15. These can be validated as per the guidelines given by USFDA.

ACKNOWLEDGMENTS

Authors acknowledge the immense help received from the scholars whose articles are cited and included in references of this manuscript. The authors are also grateful to authors / editors / publishers of all those articles, journals and books from where the literature for this article has been reviewed and discussed.

Conflict of Interest:

The authors declare that no conflict of interest for this research.

Funding:

No funding support for this research.

Contribution:

First author has developed methods and validated the proposed methods. Second author guided in entire work (preparing manuscript). Third author helped in experimental work and literature gathering.

IEC Letter no: 1074/PO/Re/S/05/CPCSEA

References:

  1. Jai Rexlin P. E, Anitha Roy, Antiviral Treatment Strategies in COVID-19. Int. J. Cur. Res Rev. 2020; 12 (21): 23-28.

  2. Scavone C, Simona B, Michele B, Liberata S, Concetta R, Alice Z, et al. Current pharmacological treatments for COVID-19: What’s next? Br. J. Pharmacol. 2020; 177(21): 1–12.

  3. Valeria A, Amedeo de N, Jessica C, Miriam A, Alessandra M,Alice P, et al. Development and validation of a UHPLC-MS/MS method for quantification of the prodrug remdesivir and its metabolite GS-441524: a tool for clinical pharmacokinetics of SARS-CoV-2/ COVID-19 and Ebola virus disease. J. Antimicrob. Chemother. 2020; 75(7): 1772-1777. 

  4. WHO (World Health Organization).Nipah Virus. 2020. Available online: https://www.who.int/news-room/fa ct-sheets/detail/nipah-virus (accessed on 25 May 2020).

  5. Michael K Lo, Friederike F, Joy M Gary, Robert J, Roy B, Jacqueline C, et al. Remdesivir (GS-5734) protects African green monkeys from Nipah virus challenge. Sci. Transl. Med. 2019 May 29; 11(494): 1-12/. Doi: 10.1126/scitranslmed.aau9242.

  6. Furuta Y, Kazumi T, Masako K, Hidehiro S, Sayuri U, Kyo K, et al. Mechanism of action of T-705 against influenza virus. Antimicrob Agents Chemother. 2005; 49(3):, 981-986.

  7. Clinicaltrials.gov. Search of: favipiravir j Covid19 - list results - clinicaltrials.Gov [online] Available at: https://clinicaltrials. Gov/ct2/results? cond¼Covid19&term¼ favipiravir&cntry¼&state¼&city¼&dist; 2020. Accessed July 23, 2020

  8. Furuta Y, Gowen BB, Takahashi K, Shiraki K, Smee DF, Barnard DL. Favipiravir (T-705), a novel viral RNA polymerase inhibitor. Antivir. Res. 2013; 100 (2):446-54.

  9. Luciano A, Emilia L, Jacob IS, Anti-Influenza Treatment: Drugs Currently Used and Under Development, Arch. Bronconeumol. 2017;53 (1); 19-26.

  10. Furuta, Y., Gowen, B.B., Takahashi, K., Shiraki, K., Smee, D.F. and Barnard, D.L. (2013) Favipiravir (T-705), a novel viral RNA polymerase inhibitor. Antivir. Res. 2013; 100(2): 446-54.

  11. ICH, Q1A, (R2) Stability Testing of New Drug Substances and Products in: IFPMA, Geneva, 2003.

  12. ICH, Q2, (R1) Validation of Analytical Procedures, in: Text and methodology, Geneva, Switzerland, 2005.

  13. Maninder Pal S, Manish K, Kashish W, Prerna.  Novel Method Development and Validation for UV–Visible Spectrophotometric Analysis of Methscopolamine Bromide. Int. J Cur. Res. Rev. 2021; 13(12): 112-117

Announcements

Dr. Pramod Kumar Manjhi joined Editor-in-Chief since July 2021 onwards

COPE guidelines for Reviewers

SCOPUS indexing: 2014, 2019 to 2021


Awards, Research and Publication incentive Schemes by IJCRR

Best Article Award: 

One article from every issue is selected for the ‘Best Article Award’. Authors of selected ‘Best Article’ are rewarded with a certificate. IJCRR Editorial Board members select one ‘Best Article’ from the published issue based on originality, novelty, social usefulness of the work. The corresponding author of selected ‘Best Article Award’ is communicated and information of award is displayed on IJCRR’s website. Drop a mail to editor@ijcrr.com for more details.

Women Researcher Award:

This award is instituted to encourage women researchers to publish her work in IJCRR. Women researcher, who intends to publish her research work in IJCRR as the first author is eligible to apply for this award. Editorial Board members decide on the selection of women researchers based on the originality, novelty, and social contribution of the research work. The corresponding author of the selected manuscript is communicated and information is displayed on IJCRR’s website. Under this award selected women, the author is eligible for publication incentives. Drop a mail to editor@ijcrr.com for more details.

Emerging Researcher Award:

‘Emerging Researcher Award’ is instituted to encourage student researchers to publish their work in IJCRR. Student researchers, who intend to publish their research or review work in IJCRR as the first author are eligible to apply for this award. Editorial Board members decide on the selection of student researchers for the said award based on originality, novelty, and social applicability of the research work. Under this award selected student researcher is eligible for publication incentives. Drop a mail to editor@ijcrr.com for more details.


Best Article Award

A Study by Humaira Tahir et al. entitled "Comparison of First Analgesic Demand after Major Surgeries of Obstetrics and Gynecology between Pre-Emptive Versus Intra-Operative Groups by Using Intravenous Paracetamol: A Cross-Sectional Study" is awarded Best Article for Vol 14 issue 14
A Study by Monica K. entitled "Risk Predictors for Lymphoma Development in Sjogren Syndrome - A Systematic Review" is awarded Best Article for Vol 14 issue 13
A Study by Mokhtar M Sh et al. entitled "Prevalence of Hospital Mortality of Critically Ill Elderly Patients" is awarded Best Article for Vol 14 issue 12
A Study by Vidya S. Bhat et al. entitled "Effect of an Indigenous Cleanser on the Microbial Biofilm on Acrylic Denture Base - A Pilot Study" is awarded Best Article for Vol 14 issue 11
A Study by Pandya S. et al. entitled "Acute and 28-Day Repeated Dose Subacute Toxicological Evaluation of Coroprotect Tablet in Rodents" is awarded Best Article for Vol 14 issue 10
A Study by Muhammad Zaki et al. entitled "Effect of Hemoglobin Level on the Severity of Acute Bronchiolitis in Children: A Case-Control Study" is awarded Best Article for Vol 14 issue 09
A Study by Vinita S & Ayushi S entitled "Role of Colour Doppler and Transvaginal Sonography for diagnosis of endometrial pathology in women presenting with Abnormal Uterine Bleeding" is awarded Best Article for Vol 14 issue 08
A Study by Prabhu A et al. entitled "Awareness of Common Eye Conditions among the ASHA (Accredited Social Health Activist) Workers in the Rural Communities of Udupi District- A Pilot Study" is awarded Best Article for Vol 14 issue 07
A Study by Divya MP et al. entitled "Non-Echoplanar Diffusion-Weighted Imaging and 3D Fiesta Magnetic Resonance Imaging Sequences with High Resolution Computed Tomography Temporal Bone in Assessment and Predicting the Outcome of Chronic Suppurative Otitis Media with Cholesteatoma" is awarded Best Article for Vol 14 issue 06
A Study by Zahoor Illahi Soomro et al. entitled "Functional Outcomes of Fracture Distal Radius after Fixation with Two Different Plates: A Retrospective Comparative Study" is awarded Best Article for Vol 14 issue 05
A Study by Ajai KG & Athira KN entitled "Patients’ Gratification Towards Service Delivery Among Government Hospitals with Particular Orientation Towards Primary Health Centres" is awarded Best Article for Vol 14 issue 04
A Study by Mbungu Mulaila AP et al. entitled "Ovarian Pregnancy in Kindu City, D.R. Congo - A Case Report" is awarded Best Article for Vol 14 issue 03
A Study by Maryam MJ et al. entitled "Evaluation Serum Chemerin and Visfatin Levels with Rheumatoid Arthritis: Possible Diagnostic Biomarkers" is awarded Best Article for Vol 14 issue 02
A Study by Shanthan KR et al. entitled "Comparison of Ultrasound Guided Versus Nerve Stimulator Guided Technique of Supraclavicular Brachial Plexus Block in Patients Undergoing Upper Limb Surgeries" is awarded Best Article for Vol 14 issue 01
A Study by Amol Sanap et al. entitled "The Outcome of Coxofemoral Bypass Using Cemented Bipolar Hemiarthroplasty in the Treatment of Unstable Intertrochanteric Fracture of Femur in a Rural Setup" is awarded Best Article Award of Vol 13 issue 24
A Study by Manoj KP et al. entitled "A Randomized Comparative Clinical Trial to Know the Efficacy of Ultrasound-Guided Transversus Abdominis Plane Block Against Multimodal Analgesia for Postoperative Analgesia Following Caesarean Section" is awarded Best Article Award of Vol 13 issue 23
A Study by Karimova II et al. entitled "Changes in the Activity of Intestinal Carbohydrases in Alloxan-Induced Diabetic Rats and Their Correction with Prenalon" is awarded Best Article of Vol 13 issue 22
A Study by Ashish B Roge et al. entitled "Development, Validation of RP-HPLC Method and GC MS Analysis of Desloratadine HCL and It’s Degradation Products" is awarded Best Article of Vol 13 issue 21
A Study by Isha Gaurav et al. entitled "Association of ABO Blood Group with Oral Cancer and Precancer – A Case-control Study" is awarded Best Article for Vol 13 issue 20
A Study by Amr Y. Zakaria et al. entitled "Single Nucleotide Polymorphisms of ATP-Binding Cassette Gene(ABCC3 rs4793665) affect High Dose Methotrexate-Induced Nephrotoxicity in Children with Osteosarcoma" is awarded Best Article for Vol 13 issue 19
A Study by Kholis Ernawati et al. entitled "The Utilization of Mobile-Based Information Technology in the Management of Dengue Fever in the Community Year 2019-2020: Systematic Review" is awarded Best Article for Vol 13 issue 18
A Study by Bhat Asifa et al. entitled "Efficacy of Modified Carbapenem Inactivation Method for Carbapenemase Detection and Comparative Evaluation with Polymerase Chain Reaction for the Identification of Carbapenemase Producing Klebsiella pneumonia Isolates" is awarded Best Article for Vol 13 issue 17
A Study by Gupta R. et al. entitled "A Clinical Study of Paediatric Tracheostomy: Our Experience in a Tertiary Care Hospital in North India" is awarded Best Article for Vol 13 issue 16
A Study by Chandran Anand et al. entitled "A Prospective Study on Assessment of Quality of Life of Patients Receiving Sorafenib for Hepatocellular Carcinoma" is awarded Best article for Vol 13 issue 15
A Study by Rosa PS et al. entitled "Emotional State Due to the Covid – 19 Pandemic in People Residing in a Vulnerable Area in North Lima" is awarded Best Article for Vol 13 issue 14
A Study by Suvarna Sunder J et al. entitled "Endodontic Revascularization of Necrotic Permanent Anterior Tooth with Platelet Rich Fibrin, Platelet Rich Plasma, and Blood Clot - A Comparative Study" is awarded Best Article for Vol 13 issue 13
A Study by Mona Isam Eldin Osman et al. entitled "Psychological Impact and Risk Factors of Sexual Abuse on Sudanese Children in Khartoum State" is awarded Best Article for Vol 13 issue 12
A Study by Khaw Ming Sheng & Sathiapriya Ramiah entitled "Web Based Suicide Prevention Application for Patients Suffering from Depression" is awarded Best Article for Vol 13 issue 11
A Study by Purushottam S. G. et al. entitled "Development of Fenofibrate Solid Dispersions for the Plausible Aqueous Solubility Augmentation of this BCS Class-II Drug" is awarded Best article for Vol 13 issue 10
A Study by Kumar S. et al. entitled "A Study on Clinical Spectrum, Laboratory Profile, Complications and Outcome of Pediatric Scrub Typhus Patients Admitted to an Intensive Care Unit from a Tertiary Care Hospital from Eastern India" is awarded Best Article for Vol 13 issue 09
A Study by Mardhiah Kamaruddin et al. entitled "The Pattern of Creatinine Clearance in Gestational and Chronic Hypertension Women from the Third Trimester to 12 Weeks Postpartum" is awarded Best Article for Vol 13 issue 08
A Study by Sarmila G. B. et al. entitled "Study to Compare the Efficacy of Orally Administered Melatonin and Clonidine for Attenuation of Hemodynamic Response During Laryngoscopy and Endotracheal Intubation in Gastrointestinal Surgeries" is awarded Best Article for Vol 13 issue 07
A Study by M. Muthu Uma Maheswari et al. entitled "A Study on C-reactive Protein and Liver Function Tests in Laboratory RT-PCR Positive Covid-19 Patients in a Tertiary Care Centre – A Retrospective Study" is awarded Best Article of Vol 13 issue 06 Special issue Modern approaches for diagnosis of COVID-19 and current status of awareness
A Study by Gainneos PD et al. entitled "A Comparative Evaluation of the Levels of Salivary IgA in HIV Affected Children and the Children of the General Population within the Age Group of 9 – 12 Years – A Cross-Sectional Study" is awarded Best Article of Vol 13 issue 05 Special issue on Recent Advances in Dentistry for better Oral Health
A Study by Alkhansa Mahmoud et al. entitled "mRNA Expression of Somatostatin Receptors (1-5) in MCF7 and MDA-MB231 Breast Cancer Cells" is awarded Best Article of Vol 13 issue 06
A Study by Chen YY and Ghazali SRB entitled "Lifetime Trauma, posttraumatic stress disorder Symptoms and Early Adolescence Risk Factors for Poor Physical Health Outcome Among Malaysian Adolescents" is awarded Best Article of Vol 13 issue 04 Special issue on Current Updates in Plant Biology to Medicine to Healthcare Awareness in Malaysia
A Study by Kumari PM et al. entitled "Study to Evaluate the Adverse Drug Reactions in a Tertiary Care Teaching Hospital in Tamilnadu - A Cross-Sectional Study" is awarded Best Article for Vol 13 issue 05
A Study by Anu et al. entitled "Effectiveness of Cytological Scoring Systems for Evaluation of Breast Lesion Cytology with its Histopathological Correlation" is awarded Best Article of Vol 13 issue 04
A Study by Sharipov R. Kh. et al. entitled "Interaction of Correction of Lipid Peroxidation Disorders with Oxibral" is awarded Best Article of Vol 13 issue 03
A Study by Tarek Elwakil et al. entitled "Led Light Photobiomodulation Effect on Wound Healing Combined with Phenytoin in Mice Model" is awarded Best Article of Vol 13 issue 02
A Study by Mohita Ray et al. entitled "Accuracy of Intra-Operative Frozen Section Consultation of Gastrointestinal Biopsy Samples in Correlation with the Final Histopathological Diagnosis" is awarded Best Article for Vol 13 issue 01
A Study by Badritdinova MN et al. entitled "Peculiarities of a Pain in Patients with Ischemic Heart Disease in the Presence of Individual Combines of the Metabolic Syndrome" is awarded Best Article for Vol 12 issue 24
A Study by Sindhu Priya E S et al. entitled "Neuroprotective activity of Pyrazolone Derivatives Against Paraquat-induced Oxidative Stress and Locomotor Impairment in Drosophila melanogaster" is awarded Best Article for Vol 12 issue 23
A Study by Habiba Suhail et al. entitled "Effect of Majoon Murmakki in Dysmenorrhoea (Usre Tams): A Standard Controlled Clinical Study" is awarded Best Article for Vol 12 issue 22
A Study by Ghaffar UB et al. entitled "Correlation between Height and Foot Length in Saudi Population in Majmaah, Saudi Arabia" is awarded Best Article for Vol 12 issue 21
A Study by Siti Sarah Binti Maidin entitled "Sleep Well: Mobile Application to Address Sleeping Problems" is awarded Best Article for Vol 12 issue 20
A Study by Avijit Singh"Comparison of Post Operative Clinical Outcomes Between “Made in India” TTK Chitra Mechanical Heart Valve Versus St Jude Mechanical Heart Valve in Valve Replacement Surgery" is awarded Best Article for Vol 12 issue 19
A Study by Sonali Banerjee and Mary Mathews N. entitled "Exploring Quality of Life and Perceived Experiences Among Couples Undergoing Fertility Treatment in Western India: A Mixed Methodology" is awarded Best Article for Vol 12 issue 18
A Study by Jabbar Desai et al. entitled "Prevalence of Obstructive Airway Disease in Patients with Ischemic Heart Disease and Hypertension" is awarded Best Article for Vol 12 issue 17
A Study by Juna Byun et al. entitled "Study on Difference in Coronavirus-19 Related Anxiety between Face-to-face and Non-face-to-face Classes among University Students in South Korea" is awarded Best Article for Vol 12 issue 16
A Study by Sudha Ramachandra & Vinay Chavan entitled "Enhanced-Hybrid-Age Layered Population Structure (E-Hybrid-ALPS): A Genetic Algorithm with Adaptive Crossover for Molecular Docking Studies of Drug Discovery Process" is awarded Best article for Vol 12 issue 15
A Study by Varsha M. Shindhe et al. entitled "A Study on Effect of Smokeless Tobacco on Pulmonary Function Tests in Class IV Workers of USM-KLE (Universiti Sains Malaysia-Karnataka Lingayat Education Society) International Medical Programme, Belagavi" is awarded Best article of Vol 12 issue 14, July 2020
A study by Amruta Choudhary et al. entitled "Family Planning Knowledge, Attitude and Practice Among Women of Reproductive Age from Rural Area of Central India" is awarded Best Article for special issue "Modern Therapeutics Applications"
A study by Raunak Das entitled "Study of Cardiovascular Dysfunctions in Interstitial Lung Diseas epatients by Correlating the Levels of Serum NT PRO BNP and Microalbuminuria (Biomarkers of Cardiovascular Dysfunction) with Echocardiographic, Bronchoscopic and HighResolution Computed Tomography Findings of These ILD Patients" is awarded Best Article of Vol 12 issue 13 
A Study by Kannamani Ramasamy et al. entitled "COVID-19 Situation at Chennai City – Forecasting for the Better Pandemic Management" is awarded best article for  Vol 12 issue 12
A Study by Muhammet Lutfi SELCUK and Fatma entitled "Distinction of Gray and White Matter for Some Histological Staining Methods in New Zealand Rabbit's Brain" is awarded best article for  Vol 12 issue 11
A Study by Anamul Haq et al. entitled "Etiology of Abnormal Uterine Bleeding in Adolescents – Emphasis Upon Polycystic Ovarian Syndrome" is awarded best article for  Vol 12 issue 10
A Study by entitled "Estimation of Reference Interval of Serum Progesterone During Three Trimesters of Normal Pregnancy in a Tertiary Care Hospital of Kolkata" is awarded best article for  Vol 12 issue 09
A Study by Ilona Gracie De Souza & Pavan Kumar G. entitled "Effect of Releasing Myofascial Chain in Patients with Patellofemoral Pain Syndrome - A Randomized Clinical Trial" is awarded best article for  Vol 12 issue 08
A Study by Virendra Atam et. al. entitled "Clinical Profile and Short - Term Mortality Predictors in Acute Stroke with Emphasis on Stress Hyperglycemia and THRIVE Score : An Observational Study" is awarded best article for  Vol 12 issue 07
A Study by K. Krupashree et. al. entitled "Protective Effects of Picrorhizakurroa Against Fumonisin B1 Induced Hepatotoxicity in Mice" is awarded best article for issue Vol 10 issue 20
A study by Mithun K.P. et al "Larvicidal Activity of Crude Solanum Nigrum Leaf and Berries Extract Against Dengue Vector-Aedesaegypti" is awarded Best Article for Vol 10 issue 14 of IJCRR
A study by Asha Menon "Women in Child Care and Early Education: Truly Nontraditional Work" is awarded Best Article for Vol 10 issue 13
A study by Deep J. M. "Prevalence of Molar-Incisor Hypomineralization in 7-13 Years Old Children of Biratnagar, Nepal: A Cross Sectional Study" is awarded Best Article for Vol 10 issue 11 of IJCRR
A review by Chitra et al to analyse relation between Obesity and Type 2 diabetes is awarded 'Best Article' for Vol 10 issue 10 by IJCRR. 
A study by Karanpreet et al "Pregnancy Induced Hypertension: A Study on Its Multisystem Involvement" is given Best Paper Award for Vol 10 issue 09

List of Awardees

A Study by Ese Anibor et al. "Evaluation of Temporomandibular Joint Disorders Among Delta State University Students in Abraka, Nigeria" from Vol 13 issue 16 received Emerging Researcher Award


A Study by Alkhansa Mahmoud et al. entitled "mRNA Expression of Somatostatin Receptors (1-5) in MCF7 and MDA-MB231 Breast Cancer Cells" from Vol 13 issue 06 received Emerging Researcher Award


RSS feed

Indexed and Abstracted in


Antiplagiarism Policy: IJCRR strongly condemn and discourage practice of plagiarism. All received manuscripts have to pass through "Plagiarism Detection Software" test before Toto Macau forwarding for peer review. We consider "Plagiarism is a crime"

IJCRR Code of Conduct: To achieve a high standard of publication, we adopt Good Publishing Practices (updated in 2022) which are inspired by guidelines provided by Committee on Publication Ethics (COPE), Open Access Scholarly Publishers Association (OASPA) and International Committee of Medical Journal Editors (ICMJE)

Disclaimer: International Journal of Current Research and Review (IJCRR) provides platform for researchers to publish and discuss their original research and review work. IJCRR can not be held responsible for views, opinions and written statements of researchers published in this journal.



ABOUT US

International Journal of Current Research and Review (IJCRR) provides platform for researchers to publish and discuss their original research and review work. IJCRR can not be held responsible for views, opinions and written statements of researchers published in this journal

Contact

148, IMSR Building, Ayurvedic Layout,
        Near NIT Complex, Sakkardara,
        Nagpur-24, Maharashtra State, India

editor@ijcrr.com

editor.ijcrr@gmail.com


Copyright © 2023 IJCRR. Specialized online journals by ubijournal .Website by Ubitech solutions