• S. PRASANTHI Department of Engineering Chemistry, AUCE (A), Andhra University, Visakhapatnam 530003, India
  • G. HIMABINDU Department of Engineering Chemistry, AUCE (A), Andhra University, Visakhapatnam 530003, India
  • YAGATI VAMSI KUMAR Department of Chemistry, Govt. Degree College (Men), Srikakulam 532001, India



Ribociclib, Letrozole, Development, Validation, Rabbit plasma


Objective: An easy, quick, precise, active and reproducible UPLC technique was developed for the bioanalytical method of Ribociclib and Letrozole using Lapatinib as the internal standard.

Methods: This article summarizes the recent progress on bioanalytical UPLC method using phenyl column (100x2.1 mm, 1.7µ) column and an organic mobile phase of 0.1% Tri fluoro acetic acid and Acetonitrile in 50:50 with a flow of 0.5 ml/min. An injection volume of 5 microliters was used. Lapatinib was used as an internal standard.

Results: The drugs were found at Letrozole (m/z 435.46/216.55), Ribociclib (m/z 506.34/167.43) and Lapatinib (internal standard, m/z 582.37/184.29), respectively. Tests were performed in less than five minutes on Ribociclib (r2 = 0.99953; concentration range: 2 to 40 ng/ml) and Letrozole (r2 = 0.99915; concentration range: 0.025 to 0.5 ng/ml). The study's precision and recovery results were determined to be accurate. Accuracy, precision, recovery, matrix effect and stability results were found to be within the suitable limits. Simple and efficient method was developed and utilized in pharmacokinetic studies to see the investigated analyte in body fluids.

Conclusion: The application denotes all the parameters of system suitability, specificity, linearity and accuracy are in good agreement with USFDA guidelines and applied effectively for the investigation of pharmacokinetic studies in rabbit.


Download data is not yet available.


Minghao W, Xiujuan W, Fan C, Yi Z, Jun J. Plasma prolactin and breast cancer risk: a meta-analysis. Sci Rep. 2016;6:25998.

Jarde T, Perrier S, Vasson MP, Caldefie Chezet F. Molecular mechanisms of leptin and adiponectin in breast cancer. Eur J Cancer. 2011;47(1):33-43. doi: 10.1016/j.ejca.2010.09.005, PMID 20889333.

Tan RB, Guay AT, Hellstrom WJ. Clinical use of aromatase inhibitors in adult males. Sex Med Rev. 2014;2(2):79-90. doi: 10.1002/smrj.23, PMID 27784593.

Riggins RB, Bouton AH, Liu MC, Clarke R. Antiestrogens, aromatase inhibitors, and apoptosis in breast cancer. Vitam Horm. 2005;71:201-37. doi: 10.1016/S0083-6729(05)71007-4, PMID 16112269.

Raymond EG, Grossman D, Weaver MA, Toti S, Winikoff B. Mortality of induced abortion, other outpatient surgical procedures and common activities in the United States. Contraception. 2014;90(5):476-9. doi: 10.1016/ j.contraception.2014.07.012, PMID 25152259.

Lee VCY, Ng EHY, Yeung WSB, Ho PC. Misoprostol with or without letrozole pretreatment for termination of pregnancy: a randomized controlled trial. Obstet Gynecol. 2011;117(2 Pt 1):317-23. doi: 10.1097/AOG.0b013e3182073fbf, PMID 21252745.

Thiruchelvam P, Walker JN, Rose K, Lewis J, Al-Mufti R. Gynaecomastia. BMJ. 2016;354:i4833. doi: 10.1136/bmj.i4833, PMID 27659195.

Chau A, Jafarian N, Rosa M. Male breast: clinical and imaging evaluations of benign and malignant entities with histologic correlation. Am J Med. 2016;129(8):776-91. doi: 10.1016/j.amjmed.2016.01.009, PMID 26844632.

Berookhim BM, Schlegel PN. Azoospermia due to spermatogenic failure. Urol Clin North Am. 2014;41(1):97-113. doi: 10.1016/j.ucl.2013.08.004, PMID 24286770.

Lotti F, Maggi M. Ultrasound of the male genital tract in relation to male reproductive health. Hum Reprod Update. 2015;21(1):56-83. doi: 10.1093/humupd/dmu042, PMID 25038770.

Schulze W. Evidence of a wave of spermatogenesis in human testis. Andrologia. 1982;14(2):200-7. doi: 10.1111/j.1439-0272.1982.tb03124.x, PMID 7103139.

Eshet R, Maor G, Ben Ari T, Ben Eliezer M, Gat-Yablonski G, Phillip M. The aromatase inhibitor letrozole increases epiphyseal growth plate height and tibial length in peripubertal male mice. J Endocrinol. 2004;182(1):165-72. doi: 10.1677/ joe.0.1820165, PMID 15225141.

Pedicelli S, Peschiaroli E, Violi E, Cianfarani S. Controversies in the definition and treatment of idiopathic short stature (ISS). J Clin Res Pediatr Endocrinol. 2009;1(3):105-15. doi: 10.4008/ jcrpe.v1i3.53, PMID 21274395.

Zhou P, Shah B, Prasad K, David R. Letrozole significantly improves growth potential in a pubertal boy with growth hormone deficiency. Pediatrics. 2005;115(2):e245-8. doi: 10.1542/peds.2004-1536, PMID 15653791.

Bulletti C, Coccia ME, Battistoni S, Borini A. Endometriosis and infertility. J Assist Reprod Genet. 2010;27(8):441-7. doi: 10.1007/s10815-010-9436-1, PMID 20574791.

Sylvestre VT, Dunton CJ. Treatment of recurrent endometrial stromal sarcoma with letrozole: a case report and literature review. Horm Cancer. 2010;1(2):112-5. doi: 10.1007/s12672-010-0007-9, PMID 21761354.

Passier A, van Puijenbroek E. Mirtazapine-induced arthralgia. Br J Clin Pharmacol. 2005;60(5):570-2. doi: 10.1111/j.1365-2125.2005.02481.x, PMID 16236049.

Meczekalski B, Podfigurna Stopa A, Genazzani AR. Hypoestrogenism in young women and its influence on bone mass density. Gynecol Endocrinol. 2010;26(9):652-7. doi: 10.3109/09513590.2010.486452, PMID 20504098.

Golob AL, Laya MB. Osteoporosis: screening, prevention, and management. Med Clin North Am. 2015;99(3):587-606. doi: 10.1016/j.mcna.2015.01.010, PMID 25841602.

Muntean AG, Pang L, Poncz M, Dowdy SF, Blobel GA, Crispino JD. Cyclin D-Cdk4 is regulated by GATA-1 and is required for megakaryocyte growth and polyploidization. Blood. 2007;109(12):5199-207. doi: 10.1182/blood-2006-11-059378, PMID 17317855.

Grossel MJ, Hinds PW. Beyond the cell cycle: a new role for Cdk6 in differentiation. J Cell Biochem. 2006;97(3):485-93. doi: 10.1002/jcb.20712, PMID 16294322.

Owen LJ, Monaghan PJ, Armstrong A, Keevil BG, Higham C, Salih Z, Howell S. Oestradiol measurement during fulvestrant treatment for breast cancer. Br J Cancer. 2019;120(4):404-6. doi: 10.1038/s41416-019-0378-9, PMID 30679781.

Szostakowska M, Trębinska Stryjewska A, Grzybowska EA, Fabisiewicz A. Resistance to endocrine therapy in breast cancer: molecular mechanisms and future goals. Breast Cancer Res Treat. 2019;173(3):489-97. doi: 10.1007/s10549-018-5023-4. PMID 30382472.

Lee SK. 011 CDK inhibitor showing early promise in drug-resistant cancers. Oncology Times. 2014;36:39-40.

Stein J, Connor S, Virgin G, Ong DE, Pereyra L. Anemia and iron deficiency in gastrointestinal and liver conditions. World J Gastroenterol. 2016;22(35):7908-25. doi: 10.3748/ wjg.v22. i35.7908, PMID 27672287.

Newburger PE, Dale DC. Evaluation and management of patients with isolated neutropenia. Semin Hematol. 2013;50(3):198-206. doi: 10.1053/j.seminhematol.2013.06.010, PMID 23953336.

Liang Q, Yao X, Tang S, Zhang J, Yau TO, Li X, Tang CM, Kang W, Lung RW, Li JW, Chan TF, Xing R, Lu Y, Lo KW, Wong N, To KF, Yu C, Chan FK, Sung JJ, Yu J On. Integrative identification of epstein–barr virus–associated mutations and epigenetic alterations in gastric cancer. Gastroenterology. 2014;147(6):1350-62.e4. doi: 10.1053/j.gastro.2014.08.036, PMID 25173755.

Balaban CD, Yates BJ. What is nausea? A historical analysis of changing views. Auton Neurosci. 2017;202:5-17. doi: 10.1016/j.autneu.2016.07.003, PMID 27450627.

DuPont HL. Acute infectious diarrhea in immunocompetent adults. N Engl J Med. 2014;370(16):1532-40. doi: 10.1056/ NEJMra1301069, PMID 24738670.

Vary JC Jr. Selected disorders of skin appendages-acne, Alopecia, Hyperhidrosis. Med Clin North Am. 2015;99(6):1195-211. doi: 10.1016/j.mcna.2015.07.003, PMID 26476248.

Potturi Ramadevi, Kantipudi Rambabu. Bioanalytical method development and validation for ezetimibe and pitavastain and its applications to pharmacokinetic studies in rabbit plasma by using LCMS/MS. IJRPS 2021;11(4):7854-62. doi: 10.26452/ ijrps.v11i4.4670.

Eluru A. Surendra Babu K. Bioanalytical method development and validation for Aplidine in rat plasma and their pharmacokinetic studies by LCMS. WJPPS. 2019;8:1201-9.

Ramchandran D, Kethipalli A, Krishnamurthy M. Bioanalytical method development and validation of daunorubicin and cytrarabine in rat plasma by LC-MS/MS and its application in pharmacokinetic studies. J Pharm Sci Res. 2020;12:381-6.

Naykode MD, Bhagwat DA, Jadhav SD, More HN. Analytical and bioanalytical method for quantification of pure azilsartan, not its salts by RP-HPLC. Res J Pharm Technol. 2017;10(3):708-14. doi: 10.5958/0974-360X.2017.00133.0.

Mayanka Singh M, Manoj Charde M, Rajesh Shukla R, Rita MC. Determination of calcipotriene in calcipotriene cream 0.05% w/w by RP-HPLC method development and validation. Research J Pharm and Technol. 2011;4:1219-23.

Malathi S, Arunadevi N. Development and validation of stability-indicating simultaneous estimation of metformin and alogliptin in tablets by high-performance thin-layer chromatography. Int J Pharm Pharm Sci. 2020;12:68-73.

Senthil Rajan D, Muruganathan G, Shivkumar K, Ganesh T. Development and validation of HPLC method for simultaneous quantification of vasicine, glycyrrhizin and piperine in poly herbal cough syrup. Int J Curr Pharm Res. 2020;12:15-9.

Palani Shanmugasundaram, Kamarapu SK, Shanmugasundaram P, Kamarapu SK. RP-HPLC method for the simultaneous estimation and validation of amlodipine besylate and atenolol in bulk and tablet dosage form in biorelevant dissolution medium (Fassif). Research J Pharm and Technol. 2017;10(10):3379-85. doi: 10.5958/0974-360X.2017.00601.1.

Gomathy S, Narenderan ST, Meyyanathan SN, Gowramma B. Development and validation of HPLC method for the simultaneous estimation of apigenin and luteolin in commercial formulation. Crit Rev. 2020;7:4785-90.

Kumar AS, Manidipa Debnath, Seshagiri Rao JVLN, Gowri Sankar D. Development and validation of a sensitive RP-HPLC method for simultaneous estimation of rosuvastatin and fenofibrate in tablet dosage form by using PDA detector in gradient mode. Research J Pharm and Tech 2016;9:549-54.

Malak Y, Al-Bathish AA, Gazy MK. El-Jamal. Rp-hplc and chemometric methods for the determination of two anti-diabetic mixtures; metformin hydrochloride-canagliflozin and metformin hydrochloride-gliclazide in their pharmaceutical formulation. Int J Pharm Pharm Sci. 2020;12:83-94.

Gadhvi MP, Bhandari A, Suhagia BN, Desai UH. Development and validation of RP-HPLC method for simultaneous estimation of atazanavir and ritonavir in their combined tablet dosage form. Research J Pharm and Technol. 2013;6:200-3.

Koya Prabhakara Rao NL, A Amara Babu, Kalyani Koganti, Babji Palakeeti. Koduri SV Srinivas. Relat subst method dev validation LC-Ms/MS method for the quantification of selexipag and its related impurities in rat plasma and its application to pharmacokinetic studies. SN Applied Sciences. 2021;3:321.

Hasanah YIF, Harahap Y, Suryadi H. Development and validation method of cyclophosphamide and 4-hydroxy cyclophosphamide with 4-hydroxy cyclophosphamide-D4 as internal standard in dried blood spots using UPLC-MS/MS. Int J Appl Pharm. 2021;13:148-52.

Naveen VMK, Veeraswami B, Srinivasa Rao G. High response bioanalytical validation approach of nadolol and bendroflumethiazide by LC-MS/MS on rat plasma. Int J Res Pharma Sci. 2020;11:2272-9.

Gowri Kusuma Kumari GK, Rambabu Kantipudi R. Bio analytical method development and validation for avapritinib in rat plasma by LC-MS/MS. J Pharm Sci Res. 2021;13:134-7.

Hemanth Kumar AK, Sudha V, Vijayakumar A, Padmapriyadarsini C. Simultaneous method for the estimation of bidaquiline and delamanid in human plasma using high-performance liquid chromatography. Int J Pharm Pharm Sci. 2021;13:36-40.

Siva Madhu Chaitanya, Srinath Nissankararao, Satya Lakshmi Gandham. A sort of validated bioanalytical method developed for the estimation of etoposide and cisplatin in rat plasma by using two different advanced liquid chromatographic techniques like HPLC and UPLC and its application in bioequivalence studies. IJRPS 2021;12(1):708-17. doi: 10.26452/ijrps.v12i1.4167.

Syed Rafi S, Kantipudi Rambabu K. Bio-analytical method development and validation of avelumab, axitinib and its application to pharmacokinetic studies in rabbit plasma by using LCMS/MS. Int J App Pharm. 2021;13:198-204. doi: 10.22159/ijap.2021v13i5.42415.



How to Cite




Original Article(s)