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  • Visible Spectrophotometric Method for the Estimation of Molnupiravir Using 1,10 Phenanthroline Reagent

  • Department of Pharmaceutical Analysis and Quality Assurance, Viswanadha Institute of Pharmaceutical Sciences, Visakhapatnam, A.P, India

Abstract

A simple, rapid, and reliable visible spectrophotometric method has been developed for the estimation of Molnupiravir, an antiviral drug, using 1,10-phenanthroline as a chromogenic reagent. The method is based on the formation of a red-colored complex between the ferrous ions, generated in situ, and 1,10-phenanthroline, in the presence of Molnupiravir which acts as a reducing agent for ferric to ferrous ions. The resulting colored complex exhibits maximum absorbance at 510 nm. The reaction conditions were optimized, and the Beer-Lambert law was found to be obeyed in the concentration range of [insert range, e.g., 1–5 µg/mL]. The method has been validated according to ICH guidelines for parameters such as linearity, accuracy, precision, limit of detection (LOD), and limit of quantitation (LOQ). . Linearity range was 1 - 5µg/ml with correlation coefficient (R2) of 0.999. LOD and LOQ were found to be 0.05831µg/ml and 0.17672µg/ml respectively. The percentage relative standard deviation for intraday precision was 1.2% and for interday precision was 0.71%.,The robustness were found to be 0.7% and ruggedness 1.0%. The proposed method was successfully applied to the estimation of Molnupiravir in bulk and pharmaceutical dosage forms without interference from common excipients. This method offers a cost-effective and efficient alternative for routine quality control analysis of Molnupiravir.

Keywords

Molnupiravir, 1,10-Phenanthroline, ferric chloride, o-phenanthroline, Methanol

Introduction

The most commonly employed reagents for the determinations are the following:

  • N-1-Naphthyl ethylene diamine dihydrochloride called as Bratton–Marshall reagent (BM reagent) undergoes diazotization for the determination of sulpha drugs, local anaesthetics, etc.
  • 3-Methyl-2- benzothiazolinone hydrazone hydrochloride, which is generally known as MBTH. The color production is depending upon the oxidative coupling of this reagent with phenols, amines, carbonyl compounds, etc.
  • Para dimethyl amino benzaldehyde (PDAB) and para dimethyl amino cinnamaldhyde (PDAC) - certain amines condenses with a variety of aldehydes in acidic media to give a product which are colored and oxidisable.
  • Phosphomolybdotungstic acid called as Folin – Ciocalteu reagent (FC reagent) undergoes oxidation, reduction (or) hydrolysis based on the functional group to be determined such as amines, phenols etc.
  • 1,2-Naphthoquinone-4-sulfonate sodium (NQS) is a chromogenic agent used for the determination of 1° aromatic amines.
  • 2,6-Dichloroquinone chloroimide, which is commonly known as GIBB'S reagent used for the identification and estimation of phenols.
  • Oxidation followed by complexation. Ex: Bathophenanthroline, 1,10 - phenanthroline, 2,2'-Bipyridine.
  • Oxidation followed by charge transfer complex formation ex: Metol-KIO3.

Oxidation Followed by Complexation

1,10-Phenanthroline   Synonym for 1,10-phenanthroline is o-phenanthroline. It is extensively chromogenic reagent used for the colorimetric or visible spectrophotometric   determination of a number of drugs and pharmaceutical substances. It is also known as ortho- phenanthroline (O- phenanthroline). It is constantly utilized in combination with a popular oxidant or oxidizing agent namely ferric chloride.

MECHANISM

The analysis of drug by using 1,10- phenanthroline involves two steps. Initially the solution of the drug under investigation is allowed to react with 1,10- phenanthroline and Ferric chloride (at elevated temperature). During this process, the drug gets oxidized and results in the generation of ferrous iron [i.e., ferric chloride is converted to ferrous chloride, i.e., (II)]. The ferrous now complexes with 1,10- phenanthroline to form an orange red colored complex. In this method, the reason of the addition of phosphoric acid is to stop the photochemical reduction. The following are the chemical reactions involved:

Drug+ FeCl3                         

           Oxidised form of drug + Fe (II).

Reduced form of Fe+3 + 1,10-Phenanthroline → (Fe+2-1,10-Phenanthroline) complex

MATERIALS AND METHODS

Chemicals and reagents: Molnupiravir (pure drug) was obtained as a gift sample from Hetero Labs. Ferric Chloride(fecl3) Grade (Thermo    Fisher Scientific India Pvt.Ltd), 1,10 Phenanathroline, Grade (Thermo Fisher Scientific India Pvt.Ltd) were purchased from Qualigens Company, Methanol, Rankem(Laboratory Reagent)  and All chemicals and reagents used were of analytical grade. Tablets containing drug Molnupiravir (Molnuvid (200mg) were procured from local market.

Instruments: Electronic Precision balance (Infra Instruments Pvt. Ltd., Chennai), PC Based Double Beam Spectrophotometer 2202 (Systronics, India).

Drug name: Molnupiravir

Structure:   

Fig.3.1: Chemical structure of Molnupiravir

Iupac Name: [(2R,3S,4R,5R)-3,4-dihydroxy-5-[(4Z)-4-(hydroxyimino)-2-oxo-1,2,3,4 tetrahydropyrimidin-1-yl] oxolan-2-yl] methyl 2- methyl propanoate

Category: Anti -viral drug.

Molecular weight: 336.35 g/mol

Molecular formula: C13H19N3O7

Melting point: 156-157?

Dosage form: Capsules

Description: White solid

pH: 7.2

Solubility:  Soluble in methanol.

Route of administration: Oral route.

Storage: Stored in a closed container at room temperature

Dose: Movfor(200mg)

Principle:                                                                 

Molnupiravir by using 1,10-Phenanthroline involves two steps. Initially the   solution of the drug Under investigation is allowed to react with 1,10-Phenanthroline and Ferric chloride (at   elevated Temperature). During this process, the drug gets oxidized and results in the generation of ferrous Iron [i.e., ferric chloride converted to ferrous chloride. The ferrous   now complexes with 1,10- Phenanthroline to form an orange red colored complex

Step:1

Step:2

Experimental Work

UV-Visible Spectrometry for Molnupiravir

Preparation of Solutions

Preparation of Stock solution: 10mg of Molnupiravir was taken in a 10ml volumetric flask, dissolved in 2ml of Methanol and made upto 10ml with Distilled water. (1mg/ml or 1000µg/ml)

Preparation of Standard solution: 1ml of stock solution was taken in a 10 ml volumetric flask, and made upto 10 ml with Distilled water (100µg/ml)

 Preparation Of 0.5% 1,10-Phenanthroline: 500mg 0f 1,10-Phenanthroline was taken in a 100ml volumetric flask , dissolved in 2 ml of methanol and made upto 10ml with Distilled water.

Preparation Of 0.3% Fecl3 : 300mg of Fecl3 was taken in a 100ml volumetric flask , dissolved in 2 ml of methanol and made upto 10ml with Distilled water.

Method Development

Determination Of Λ Max of Molnupiravir

Preparation of solution: 1ml of standard drug solution (100µg/ml) was taken in a 10ml volumetric flask, 1ml of ferric chloride and 1,10-phenanthroline reagent (0.5%) was added. It was heated for 15mins in a water bath for colour development and was allowed to cool. Then it was made up to 10ml with distilled water.

Preparation of blank solution: 1ml of ferric chloride and 1,10-phenanthroline was taken in 10ml of volumetric flask, then it was heated for 15mins. Then it was allowed to cool and made upto 10ml with distilled water.

Fig:  λmax of Molnupiravir using 1,10-Phenanthroline

S. No

Wavelength(nm)

Absorbance

1

400

0.284

2

405

0.293

3

410

0.305

4

415

0.312

5

420

0.329

6

425

0.341

7

430

0.353

8

435

0.384

9

440

0.402

10

445

0.419

11

450

0.443

12

455

0.465

13

460

0.478

14

465

0.504

15

470

0.526

16

475

0.537

17

480

0.564

18

485

0.583

19

490

0.607

20

495

0.635

21

500

0.672

22

505

0.724

23

510

0.748

24

515

0.735

25

520

0.712

26

525

0.698

27

530

0.683

28

535

0.492

29

540

0.398

30

545

0.378

31

550

0.238

32

555

0.202

33

560

0.158

Absorption Spectrum of Molnupiravir

Result: The absorption maximum (λmax) of Molnupiravir was found to be 510 nm

Optimization Of (0.3%) Fecl3 Solution

S. No

Contents in flask

Absorbance

Blank

Sample

  1.  

0.5 ml of FeCl3 +1ml of 1,10-PTL then heat it for 15min and made up to 10ml with distilled water

1ml working standard solution + 0.5ml of FeCl3 +1ml of 1,10- PTL then heat it for 15 min and made up to 10ml with distilled water

0.122

  1.  

1 ml of FeCl3 +1ml of 1,10-   PTL then heat it for 15 min and made up to 10ml with distilled water

1ml working standard solution + 1ml of FeCl3 +1ml of 1,10- PTL then heat it for 15 min and made up to 10ml with distilled water

0.259

  1.  

1.5 ml of FeCl3 +1ml of 1,10- PTL then heat it for 15 min and made up to 10ml with distilled water

1ml working standard solution + 1.5ml of FeCl3 +1ml of 1,10- PTL then heat it for 15 min and made up to 10ml with distilled water

0.135

  1.  

2 ml of FeCl3 +1ml of 1,10-   PTL of then heat it for 15 min and made up to 10ml with distilled water

1ml working standard solution+ 2ml of FeCl3 +1ml of 1,10- PTL then heat it for 15 min and made up to 10ml with distilled water

0.142

  1.  

2.5 ml of FeCl3 +1ml of 1,10- PTL then heat it for 15 min and made up to 10ml with distilled water

1ml working standard solution+ 2.5ml of FeCl3 +1ml of 1,10- PTL then heat it for 15 min and made up to 10ml with distilled water

0.156

Result: The optimium volume of 0.3% Fecl3 was found to be 1.0.ml

Optimization Of 0.5% 1,10- Phenanthroline Solution

S. No

Contents in flask

Absorbance

Blank

Sample

  1.  

1ml of FeCl3+0.5ml of 1,10-PTL then heat it for 15 min and made up to 10ml with distilled water

1ml stock solution + 1 ml of FeCl3+0.5ml of 1,10- PTL then heat it for 15 min and made up to 10ml with distilled water

0.129

  1.  

1ml of FeCl3+1ml of 1,10-PTL then heat it for 15 min and made up to 10ml with distilled water

1ml stock solution+ 1 ml of FeCl3 +1ml of 1,10- PTL then heat it for 15 min and made up to 10ml with distilled water

0.156

  1.  

1 ml of FeCl3 +1.5ml of 1,10- PTL then heat it for 15 min and made up to 10ml with distilled water

1ml stock solution+1ml of                                                FeCl3 +1.5ml of 1,10- PTL then heat it for 15 min and made up to 10ml with distilled water

0.228

  1.  

1ml of FeCl3 +2ml of 1,10- PTL of then heat it for 15 min and made up to 10ml with distilled water

1ml stock solution+1ml of FeCl3 +2ml of 1,10- PTL then heat it for 15 min and made up to 10ml with distilled water

0.285

  1.  

1ml of FeCl3 +2.5ml of 1,10-PTL then heat it for 15 min and made up to 10ml with distilled water

1ml stock solutio+1ml of FeCl3+2.5ml of 1,10-PTL then heat it for 15min and made up to 10ml with distilled water

0.240

Result: The optimum volume of 0.5% 1,10 Phenanthroline was found to be 2.0.ml

Method Validation

Linearity

Preparation of linearity solutions:

1mcg/ml Solution: 0.1ml of standard solution was taken, 1ml of fecl3(0.3%) and 2ml of 1,10-PTL (0.5%) was added. It was heated for 15 mins in a water bath for colour development and it was allowed to cool. Then it was made upto 10ml with distilled water.

2mcg/ml Solution: 0.2ml of standard solution was taken, 1ml of fecl3(0.3%) and 2ml of 1,10- PTL (0.5%) was added. It was heated for 15 mins in a water bath for colour development and it was allowed to cool. Then it was made upto 10ml with distilled water.

3mcg/ml Solution: 0.3ml of standard solution was taken, 1ml of fecl3(0.3%) and 2ml of 1,10- PTL (0.5%) was added. It was heated for 15 mins in a water bath for colour development and it was allowed to cool. Then it was made upto 10ml with distilled water.

4mcg/ml Solution: 0.4ml of standard solution was taken, 1ml of fecl3(0.3%) and 2ml of 1,10-PTL (0.5%) was added. It was heated for 15 mins in a water bath for colour development and it was allowed to cool. Then it was made upto 10ml with distilled water.

5mcg/ml Solution: 0.5ml of standard solution was taken, 1ml of fecl3(0.3%) and 2ml of 1,10-PTL (0.5%) was added. It was heated for 15 mins in a water bath for colour development and it was allowed to cool. Then it was made upto 10ml with distilled water.

Preparation of blank solution: 1ml of fecl3(0.3%) and 2ml of 1,10- PTL (0.5%) was added and then heated for 15 mins. Then it was allowed to cool and made upto 10ml with distilled water.

The absorbances of the solutions were observed.

Linearity data of Molnupiravir

Concentration(µg/ml)

Absorbance

1.0

0.174

2.0

0.359

3.0

0.541

4.0

0.732

5.0

0.909

A calibration curve or standard curve was plotted by taking concentration (mcg/ml) on X-axis and absorbance on Y-axis. Linearity equation (y=mx+c) and correlation coefficient (R2) was determined from the calibration curve.

Result: The linearity range- 1-5µg/ml

Correlation coefficient (R2) value obtained was 0.999

Precision

Preparation of 3mcg/ml solution: 0.3ml of standard solution was taken, 1ml of fecl3(0.3%) and 2ml of 1,10- PTL (0.5%) was added. It was heated for 15 mins in a water bath for colour development and it was allowed to cool. Then it was made upto 10ml with distilled water.

Preparation of Blank: 1ml of fecl3(0.3%) and 2ml of 1,10- PTL (0.5%) was added and then heated for 15 mins. Then it was allowed to cool and made upto 10ml with distilled water.

Intraday precision: 6 determinations of 0.3mcg/ml solution were done 3 times in a day and observed for absorbance.

Intraday precision data of Molnupiravir

S.NO

Morning

Afternoon

Evening

  1.  

0.545

0.539

0.537

  1.  

0.540

0.538

0.536

  1.  

0.542

0.540

0.539

  1.  

0.544

0.543

0.542

  1.  

0.539

0.538

0.537

  1.  

0.546

0.544

0.543

% RSD

1.1%

1.1%

1.4%

Result: %RSD for intraday precision was found to be 1.2%

Interday precision: 6 determinations of 0.3mcg/ml solution were done 3 consecutive days and observed for absorbance.

S.NO

Day– 1

Day– 2

Day-3

  1.  

0.550

0.546

0.544

  1.  

0.546

0.543

0.538

  1.  

0.543

0.540

0.536

  1.  

0.548

0.544

0.543

  1.  

0.541

0.539

0.537

  1.  

0.540

0.538

0.537

Result: %RSD for interday precision was found to be 0.71%.

Robustness: 6 determinations of 0.3mcg/ml solution were done and observed for absorbance at different wavelength (nm) with respect to optimized wavelength.

Robustness data of Molnupiravir

508nm

510nm

512nm

0.542

0.544

0.545

0.534

0.539

0.540

0.540

0.538

0.538

0.535

0.543

0.544

0.533

0.536

0.537

0.531

0.545

0.546

Result: %RSD for wavelength of 508nm was found to be 0.7%

              %RSD for wavelength of 510nm was found to be 0.7%

              %RSD for wavelength of 512nm was found to be 1.1%

Ruggedness: 6 determinations of 0.3mcg/ml solution was done by two different analysts and observed for absorbances.

Ruggedness data of Molnupiravir

Analyst– 1

Analyst-2

0.544

0.543

0.545

0.544

0.537

0.536

0.546

0.545

0.538

0.538

0.540

0.539

Result: %RSD for analyst-1 was found to be 1.1%

             %RSDforanalyst-2 was found to be 0.9%

Limit of Detection:

LOD=3.3σ/S
    σ=standard deviation of intercept S = slope

    σ=standard error of intercept* √N

SD intercept= 0.003232

Slope = 0.182886

LOD =3.3 ×SD intercept / Slope

=3.3×0.003232÷0.182886

=0.05831

Limit of Quantification:

LOQ=10σ/S
σ=standard deviation of intercept S = slope

σ=standard error of intercept*√N

SD intercept= 0.003232

Slope = 0.182886

LOQ =10×SDintercept/ Slope

=10 ×0.003232÷0.182886

=0.17672

RESULTS AND DISCUSSION

Parameters

Molnupiravir

Wavelength (nm)

510nm

Linearity range (μg/ml)

1-5μg/ml

Regression equation

Slope (m)

Intercept(c)

Y= 0.182x-0.004

0.182

0.004

Correlation coefficient

0.999

Precision (%RSD)

1. Intra day

2.Inter day

 

1.2%

0.9%

Robustness (%RSD)

  1. Wavelength 508nm
  2. Wavelength 510nm
  3. Wavelength 512nm

 

0.7%

0.7%

1.1%

Ruggedness (%RSD)

  1. Analyst-1
  2. Analyst-2

 

1.1%

0.9%

Limit of detection(µg/ml)

0.05831

Limit of quantification (µg/ml)

0.17672

CONCLUSION:

A simple, sensitive, linear, precise and robust Visible Spectrophotometric method was developed for the determination of Molnupiravir using 1,10phenantroline reagent. The developed method was validated as per ICH guidelines. The % RSD for precision. robustness and ruggedness were found to be within the limits. The developed method has lower range of linearity which indicates that the method is more sensitive even at lower concentrations. Therefore, the developed method can be recommended for routine analysis of Molnupiravir.                                          

REFERENCE

  1. A Textbook of Pharmaceutical Analysis. Dr. S. Ravi Shankar. Edition – 4. Pg. No: 1-1, 1-4 & 1-5.
  2. Instrumental Analysis. Skoog, Holler, Crouch. Pg. No: 13-14.
  3. Instrumental Method of Analysis. Gurdeep R. Chatwal, Sham K. Anand. Himalaya Publishing House. Revised 5th edition. Pg. No: 2.107 - 2.112.
  4. Instrumental Method of Analysis. Willard, Merritt, Dean, Settle. 7th Edition. Pg. No: 118– 154.
  5. Pharmaceutical Drug Analysis. Ashutosh Khar. New Age International Publishers Revised 2nd Edition. Pg. No: 303-304.
  6. N. Karnakar, H. Ramana, P. Amani, D. Sri Tharun, M. Nagaraju, Saurabh Bodhgaya Sharma. International Journal of Multidisciplinary Research and Development. 2020, 7, 23-24.
  7. Panchumarthy Ravisankar, MD. Shaheem Sulthana, P. S. Babu, SK. Afzal Basha, R. Aswini, V. Swathi, SK. Mahamuda Sultana, M. Sri Lakshmi Prasanna, N. Navyasri, I. M. Thanuja. Comprehensive Review of Important Analytical Reagents used in Spectrophotometry. Indo American Journal of Pharmaceutical Research. 2017, 7(5), 8716-8744.
  8. Sujan Banik, MD Masud Kaisar, Mohammad Salim Hussain. Development and validation of simple UV Spectrophotometric method for estimation of Linagliptin in Bulk and Marketed dosage form. Indian Journal of Novel Drug Delivery. 2013, 5(4), 221-224.
  9. Amruta Dalal, Dr.Varsha Tegeli and Rajashri Waghmode. Development and validation of simple UV Spectrophotometric method for estimation of Linagliptin in Bulk and Marketed dosage form. Der Pharma Chemica. 2022, 14(2).
  10. Deepika Joshi, Bhavana Singh, Archana Rautela and Nidhi Semwal. Analytical method Development and Validation of UV Visible Spectrophotometric method for estimation of Linagliptin. Global Journal of Nanomedicine. 2021, 5(5).
  11. Manish Mishra and Govinda Verma. Analytical method Development and Validation for Determination of Linagliptin in Bulk and Dosage form by UV Spectroscopy. Journal of Emerging Technologies and Innovative Research. 2018, 5(7), 908-912.
  12. K. Vijaya Sri, A. Anusha, M. Sudhakar. UV-Spectrophotometry Method for the Estimation of Linagliptin in Bulk and Pharmaceutical Formulations. Asian J. Research Chem. 2016, 9(1), 47-50.
  13. Zalte Amar Gangadhar, Ravindranath Bhanudas Saudagar, Pramod Nanasaheb Katkade. Validated UV- Spectroscopic estimation of Linagliptin Concentration in Bulk and Dosage form. Research J. Pharm. and Tech. 2016, 9(5), 490-492.
  14. Sunitha Gurrala, Panikumar Durga Anumolu, Sahitya Menkana, Nikitha Gandla, Keerthi Toddi. hai Journal of Pharmaceutical Sciences. 2020, 44 (4), 245-250.
  15. Lujain Sahloul & Maisam Salami. Development and validation of a new analytical method for determination of linagliptin in bulk by visible spectrophotometer. Scientific Reports. 2023, 13, 4083.
  16. https://en.wikipedia.org › wiki › Linagliptin
  17. Maisha Kelly Freeman. Efficacy and Safety of Linagliptin (Tradjenta) in Adults with Type-2 Diabetes Mellitus. Pharmacy and Therapeutics. 2011, 36(12), 807-812
  18. Stefan Blech, Eva Ludwig-Schwellinger, Eva Ulrike Gräfe - Mody, Barbara Withopf and Klaus Wagner. The Metabolism and Disposition of the Oral Dipeptidyl Peptidase-4 Inhibitor, Linagliptin, in Humans. Drug Metabolism and Disposition. 2010, 38 (4), 667-678.
  19. Ulrike Graefe-Mody, Silke Retlich, Christian Friedrich. Clinical pharmacokinetics and Pharmacodynamics of linagliptin. Clin Pharmacokinet. 2012, 51(7), 411-27
  20. Linagliptin Oral: Uses, Side Effects, Interactions, Pictures, Warnings & Dosing -WebMD.

Reference

  1. A Textbook of Pharmaceutical Analysis. Dr. S. Ravi Shankar. Edition – 4. Pg. No: 1-1, 1-4 & 1-5.
  2. Instrumental Analysis. Skoog, Holler, Crouch. Pg. No: 13-14.
  3. Instrumental Method of Analysis. Gurdeep R. Chatwal, Sham K. Anand. Himalaya Publishing House. Revised 5th edition. Pg. No: 2.107 - 2.112.
  4. Instrumental Method of Analysis. Willard, Merritt, Dean, Settle. 7th Edition. Pg. No: 118– 154.
  5. Pharmaceutical Drug Analysis. Ashutosh Khar. New Age International Publishers Revised 2nd Edition. Pg. No: 303-304.
  6. N. Karnakar, H. Ramana, P. Amani, D. Sri Tharun, M. Nagaraju, Saurabh Bodhgaya Sharma. International Journal of Multidisciplinary Research and Development. 2020, 7, 23-24.
  7. Panchumarthy Ravisankar, MD. Shaheem Sulthana, P. S. Babu, SK. Afzal Basha, R. Aswini, V. Swathi, SK. Mahamuda Sultana, M. Sri Lakshmi Prasanna, N. Navyasri, I. M. Thanuja. Comprehensive Review of Important Analytical Reagents used in Spectrophotometry. Indo American Journal of Pharmaceutical Research. 2017, 7(5), 8716-8744.
  8. Sujan Banik, MD Masud Kaisar, Mohammad Salim Hussain. Development and validation of simple UV Spectrophotometric method for estimation of Linagliptin in Bulk and Marketed dosage form. Indian Journal of Novel Drug Delivery. 2013, 5(4), 221-224.
  9. Amruta Dalal, Dr.Varsha Tegeli and Rajashri Waghmode. Development and validation of simple UV Spectrophotometric method for estimation of Linagliptin in Bulk and Marketed dosage form. Der Pharma Chemica. 2022, 14(2).
  10. Deepika Joshi, Bhavana Singh, Archana Rautela and Nidhi Semwal. Analytical method Development and Validation of UV Visible Spectrophotometric method for estimation of Linagliptin. Global Journal of Nanomedicine. 2021, 5(5).
  11. Manish Mishra and Govinda Verma. Analytical method Development and Validation for Determination of Linagliptin in Bulk and Dosage form by UV Spectroscopy. Journal of Emerging Technologies and Innovative Research. 2018, 5(7), 908-912.
  12. K. Vijaya Sri, A. Anusha, M. Sudhakar. UV-Spectrophotometry Method for the Estimation of Linagliptin in Bulk and Pharmaceutical Formulations. Asian J. Research Chem. 2016, 9(1), 47-50.
  13. Zalte Amar Gangadhar, Ravindranath Bhanudas Saudagar, Pramod Nanasaheb Katkade. Validated UV- Spectroscopic estimation of Linagliptin Concentration in Bulk and Dosage form. Research J. Pharm. and Tech. 2016, 9(5), 490-492.
  14. Sunitha Gurrala, Panikumar Durga Anumolu, Sahitya Menkana, Nikitha Gandla, Keerthi Toddi. hai Journal of Pharmaceutical Sciences. 2020, 44 (4), 245-250.
  15. Lujain Sahloul & Maisam Salami. Development and validation of a new analytical method for determination of linagliptin in bulk by visible spectrophotometer. Scientific Reports. 2023, 13, 4083.
  16. https://en.wikipedia.org › wiki › Linagliptin
  17. Maisha Kelly Freeman. Efficacy and Safety of Linagliptin (Tradjenta) in Adults with Type-2 Diabetes Mellitus. Pharmacy and Therapeutics. 2011, 36(12), 807-812
  18. Stefan Blech, Eva Ludwig-Schwellinger, Eva Ulrike Gräfe - Mody, Barbara Withopf and Klaus Wagner. The Metabolism and Disposition of the Oral Dipeptidyl Peptidase-4 Inhibitor, Linagliptin, in Humans. Drug Metabolism and Disposition. 2010, 38 (4), 667-678.
  19. Ulrike Graefe-Mody, Silke Retlich, Christian Friedrich. Clinical pharmacokinetics and Pharmacodynamics of linagliptin. Clin Pharmacokinet. 2012, 51(7), 411-27
  20. Linagliptin Oral: Uses, Side Effects, Interactions, Pictures, Warnings & Dosing -WebMD.

Photo
B. Rama Madhuri
Corresponding author

Department of Pharmaceutical Analysis and Quality Assurance, Viswanadha Institute of Pharmaceutical Sciences, Visakhapatnam, A.P, India

Photo
Dr. P. V. Madhavi Latha
Co-author

Department of Pharmaceutical Analysis and Quality Assurance, Viswanadha Institute of Pharmaceutical Sciences, Visakhapatnam, A.P, India

Photo
M. Swapna
Co-author

Department of Pharmaceutical Analysis and Quality Assurance, Viswanadha Institute of Pharmaceutical Sciences, Visakhapatnam, A.P, India

B. Rama Madhuri*, Dr. P. V. Madhavi Latha, M. Swapna, Visible Spectrophotometric Method for the Estimation of Molnupiravir Using 1,10 Phenanthroline Reagent, Int. J. Sci. R. Tech., 2025, 2 (11), 101-110. https://doi.org/10.5281/zenodo.17530391

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