Author(s): Sunandana Akkala, Govinda Gopalakrishna Kilaru, Gopi Bandreddy, Suman Baindla Madhusudhan Gutta

Email(s): gopalkilaru@gmail.com

DOI: 10.52711/2231-5691.2024.00031   

Address: Sunandana Akkala, Govinda Gopalakrishna Kilaru, Gopi Bandreddy, Suman Baindla Madhusudhan Gutta*
Vijayasri Organics, IDA Bolloram, Jinnaram, Medak, Telangana-502325.
*Corresponding Author

Published In:   Volume - 14,      Issue - 2,     Year - 2024


ABSTRACT:
Genotoxic impurity free Molnupiravir was synthesised by a novel and an elegant non-enzymatic method, which is simple operationally and ecologically. The genotoxic raw material, Hydroxylamine, was used in the initial stages of synthesis to get the mutagenic impurity free Molnupiravir. A new and sensitive HPLC method was developed and validated for the determination of hydroxylamine in Molnupiravir drug substance according to ICH guidelines. The HPLC method was developed and optimized on Zorbax SB C18 150×4.6mm, 3.5µm column with oven temperature maintained at 40°C. 1.0 mL of Orthophosphoric acid in 1000 mL water was selected as mobile phase in isocratic reverse phase mode. Chromatographic parameters are flow rate: 0.8 ml/min, wavelength detection: 252 nm, injection volume: 10µl and run time: 20 min. Based on the validation data; the method was found to be specific, sensitive, accurate and precise. This method can be used as a good quality control tool for quantification of hydroxylamine at the low level. The experimental data was deliberated in detail in this research paper.


Cite this article:
Sunandana Akkala, Govinda Gopalakrishna Kilaru, Gopi Bandreddy, Suman Baindla Madhusudhan Gutta. Two Steps Non-Enzymatic Synthesis of Molnupiravir, which is Free from Mutagenic Impurity and Analytical Method Development for Estimation of Genotoxic Impurity (Hydroxylamine Hydrochloride Content) by using RP-HPLC Technique. Asian Journal of Pharmaceutical Research. 2024; 14(2):188-6. doi: 10.52711/2231-5691.2024.00031

Cite(Electronic):
Sunandana Akkala, Govinda Gopalakrishna Kilaru, Gopi Bandreddy, Suman Baindla Madhusudhan Gutta. Two Steps Non-Enzymatic Synthesis of Molnupiravir, which is Free from Mutagenic Impurity and Analytical Method Development for Estimation of Genotoxic Impurity (Hydroxylamine Hydrochloride Content) by using RP-HPLC Technique. Asian Journal of Pharmaceutical Research. 2024; 14(2):188-6. doi: 10.52711/2231-5691.2024.00031   Available on: https://www.asianjpr.com/AbstractView.aspx?PID=2024-14-2-16


REFERENCES:
1.    WO2019113462 - n4-hydroxycytidine and derivatives and anti-viral uses related there to painter, George, R.Bluemling, Gregory, R.Natchus, Michael, G.Guthrie, David
2.    CN112608357 - preparation method of antiviral drug molnupiravir
3.    A High-Yielding Synthesis of EIDD-2801 from Uridine Steiner, Alexander; Znidar, Desiree; Oetvoes, Sandor B.; Snead, David R.; Dallinger, Doris; Kappe, C. Oliver
4.    A convenient and cost efficient route suitable for “one-pot” synthesis of molnupiravir Tianwen Hu, 7ac Yuanchao Xie, and B Yin Liu, Bc Haitao Xue, BC Fuqiang Zhu, d Haji A. Aisa, AC and Jingshan Shen. A Concise Route to MK-4482 (EIDD-2801) from Cytidine.
5.    Vasudevan, N.; Ahlqvist, Grace P.; McGeough, Catherine P.; Paymode, Dinesh J.; Cardoso, Flavio S.P.; Lucas, Tobiasc; Dietz, Jule-Phillip; Opatz, Tillc; Jamison, Timothy, F.; Gupton, B. Frank; Snead, David R. Toward a Practical, Two-Step Process for Molnupiravir from Cytidine
6.    Dinesh J. Paymode, Natarajan Vasudevan, Saeed Ahmad, Appasaheb L. Kadam, Flavio S. P. Cardoso, Justina Burns, Daniel W. Cook, Rodger W. Stringham, David Snead
7.    ICH guidelines for mutagenicity, ICH guideline M7(R1) on assessment and control of DNA reactive (mutagenic) impurities in pharmaceuticals to limit potential carcinogenic risk
8.    Determination of Hydroxylamine hydrochloride by modified method based on photoluminescence of   Silver nanoparticles. Tavallali, Hossein; Maharloey, Nargess Rrahnama.
9.    Determination of Hydroxylamine by HPLC, a Mutagenic Impurity in Febuxostat Drug Substance V.Saradhi Venkata Ramana, K. Durga Raja, K.Raghu Babu, M.Padma, Vundavilli Jagadeesh Kumar, K. S. R. Pavan Kumar , Hemant Kumar Sharma
10.    Liquid chromatography method to analyze genotoxic   impurity hydroxylamine in pharmaceutical product. Ajit Anerao, Vikram Dighe, Anand Gupta and Vishal Solse
11.    ICH guidelines for analytical method validations
12.    Quantitative measurement of trace levels of residual hydroxylamine hydrochloride by a simple gas chromatographic mehod and its application in drug substance Prabhune, Swarup; Darsi, Praveen Kumar; Gangrade, Manish; Jaychandran, Jeenet
13.    Spectrophotometric determination of hydroxylamine and its derivatives in pharmaceutical formulations George, Mary; Nagaraja, K. S.; Balasubramanian, N.
14.    Spectrophotometric determination of hydroxylamine and its derivatives in drug formulation using methyl red. George, Mary; Balasubramanian, N.; Nagaraja, K. S.
15.    A selective and sensitive pre-column derivatization HPLC method for the trace analysis of genotoxic impurity hydroxylamine in active pharmaceutical ingredients Song, Min; Wu, Sha; Lu, Ping-bo; Qiao, Ya-nan; Hang, Tai-jun
16.    A Simple and Direct LC–MS Method for Determination of Genotoxic Impurity Hydroxylamine in Pharmaceutical compounds Thangarathinam Kumar, Mohandass Ramya, Viswanathan Srinivasan, and N. Xavier
17.    Simultaneous analysis by LC–MS/MS of 22 ketosteroids with hydroxylamine derivatization and underivatized   estradiol from human plasma, serum and prostate tissue
18.    Determination of hydroxylamine genotoxic impurity by derivatization in penicillamine drug   substance by GCHS-MS.  Ravi Uppala, M. Arthanareeswari
19.    Development and Validation of Estimation of Genotoxic Impurity (Hydroxylamine Hydrochloride Content) in Leflunomide by using RP-HPLC Technique Mohan Bhatale, Neelakandan Kaliyaperumal, Gopalakrishnan Mannathusamy
20.    A Novel RP-HPLC Method Development and     Validation for the Determination of Pioglitazone and Glimepiride in Bulk and Pharmaceutical Formulations. Asian J. Pharm. Ana. 2017; 7(3): 145-150.   Ashwini Parmar, Sandeep Sonawane, Santosh Chhajed, Sanjay Kshirsagar.
21.    Development and Validation of RP-HPLC Method for simultaneous estimation of Telmisartan, Amlodipine Besylate and Hydrochlorthiazide in their tablet dosage form. Asian J. Pharm. Ana. 2017; 7(3): 189-195.O. S. S.Chandana, R. Ravichandra Babu.
22.    Method Development and Validation of Valsartan and Its Impurities by High Performance Liquid Chromatography. Asian J. Pharm. Ana. 2017; 7(2): 87-92. K. Vijaya Sri, S. Sruthi, M.A. Madhuri.
23.    Rapid RP-HPLC Method Development and Validation of Tolvaptan in Bulk and Pharmaceutical Dosage Form for an Internal Standard. Asian J. Pharm. Ana. 2017; 7(1): 36-40. Neeta, Harish Dureja.
24.    Reverse Phase High-Performance Liquid Chromatographic Estimation and In vitro    Cytotoxicity of Boswellic Acids on A-375 Melanoma Cancer Cell lines. Asian J. Pharm. Ana. 2018; 8(1): 13-19.  S. J. Daharwal, Veena D. Singh.
25.    Development of chemometric assisted methods for Simultaneous estimation of Ternary mixture of Telmisartan hydrochloride, Amlodipine besylate and Hydrochlorothiazide. Asian J. Pharm. Tech. 2015; Vol. 5: Issue 2, Pg 122-126. Monika A. Rana, Hasumati A. Raj.
26.    Simple Validated Spectroscopic Method for Estimation of Amlodipine Besylate from Tablet Formulation. Asian J. Research Chem. 2(4): Oct.-Dec. 2009 page 553-555 MD Wandhare, UA Deokate, SS Khadabadi, SP Hadke, HA Sawarkar
27.    Development and Validation of High Performance Liquid Chromatography Method for Levosulpiride and its Intermediate in Synthetic Mixture. Asian J. Pharm. Tech. 2015; Vol. 5: Issue 2, Pg 97-106 Pallavi Salve, Deepali Gharge, Rupali Kirtawade, Pandurang Dhabale, Kishor Burade.
28.    Comparative Estimation of Curcumin Content from Marketed Herbal Anti Rheumatic Tablets Formulation. Asian J. Research Chem. 2(3): July-Sept., 2009, page 340-343.Sunakar Panda, Swapna Sankar Nayak.
29.    Inclusion Complexes of Acridone and Its Semicarbazone Derivative With β- Cyclodextrin: - A Thermodynamic, Spectral and Antimicrobial Study. Asian J. Research Chem. 2(4): Oct.-Dec. 2009 page 539-543.















Recomonded Articles:

Author(s): Hiral A. Makadia, Ami Y. Bhatt, Ramesh B. Parmar, Ms. Jalpa S. Paun, H.M. Tank

DOI:         Access: Open Access Read More

Author(s): Neha Meshram, Mithlesh Ojha, Ajay Singh, Amit Alexander, Ajazuddin, Mukesh Sharma

DOI: 10.5958/2231-5691.2015.00009.X         Access: Open Access Read More

Author(s): Ayesha Anees, Asra Ali Bahazeq, MD. Muzaffar-Ur-Rehman, Syed Akbar, Juveria Mehveen

DOI: 10.5958/2231-5691.2019.00011.X         Access: Open Access Read More

Author(s): Pavan Chavan, Sandip Bandgar, Santosh Gejage, Sagar Patil, Shitalkumar Patil

DOI: 10.5958/2231-5691.2021.00004.6         Access: Open Access Read More

Author(s): Girish Pai K., Vamshi Krishna T., Lalit Kumar, M. Sreenivasa Reddy, G. Shreenidhi, A. Praneeth Reddy

DOI:         Access: Open Access Read More

Author(s): Prabhu Venkatesh Moodbidri, Varadaraji Dhayanithi, Ganesh Belavadi Manjunathashastry, Hari Narayan Pati , Pardhasaradhi Vasireddy

DOI: 10.5958/2231-5691.2015.00027.1         Access: Open Access Read More

Author(s): Tandel Jinal N., Pumbhadiya Dilipkumar A., Chauhan Payal P, Shah Samir K

DOI: 10.5958/2231-5691.2018.00001.1         Access: Open Access Read More

Author(s): Kasad Pinaz A, K.S. Muralikrishna

DOI:         Access: Open Access Read More

Author(s): Anand Gupta, Vaishali Jadhav, Ashish Jain

DOI: 10.5958/2231-5691.2019.00022.4         Access: Open Access Read More

Author(s): Sufiyan Ahmad, Ansari Sajjad, Md. Rageeb Md. Usman, Mohammed Imran, Rashid Akhtar

DOI: 10.5958/2231-5691.2017.00022.3         Access: Open Access Read More

Author(s): Sravani Koralla, Sathish Kumar Konidala, K Govinda Rao, Sheik Mobina Begum

DOI:         Access: Open Access Read More

Author(s): Revathi R, Ethiraj T, Chandru S, Dilip I, Faisul Rahman S

DOI: 10.5958/2231-5691.2019.00012.1         Access: Open Access Read More

Asian Journal of Pharmaceutical Research (AJPRes.) is an international, peer-reviewed journal, devoted to pharmaceutical sciences. AJPRes. publishes Original Research Articles, Short Communications..... Read more >>>

RNI: Not Available                     
DOI: 10.5958/2231–5691 


Recent Articles




Tags