ESTIMATION OF ETONOGESTREL IN HUMAN PLASMA BY USING LC–ESI–MS/MS METHOD


Satish Ramanatham Velamakanni, Venkateswarlu Padala

Abstract


Objective: The aspiration of the present study was to develop simple, robust and reliable liquid chromatography/electro spray ionization tandem mass spectrometry (LC-MS/MS) (Agilent Technologies) assay method for the quantification of etonogestrel in human serum by using etonogestrel d6 as internal standard (IS).

Methods: An easy Liquid-Liquid Extraction (LLE) sample processing method was used to extract etonogestrel from plasma and chromatographic method was developed with run time 3.5min with linear calibration curve ranges from 50-3604 pg/mL for both etonogestrel and etonogestrel d6 and chromatographic method validated by determining carryover test, sensitivity, matrix effect, linearity, precision, accuracy, recovery, dilution integrity and stability. The developed method was used for pharmacokinetic study of 75mcg desogestrel tablet formulation under fasting condition in healthy females.

Results: The validation showed the developed method was accurate with the results of validated parameters were met acceptance criteria as per Food and Drug Administration (FDA) guidelines. The validated method successfully was used for pharmacokinetic study of 75mcg desogestrel tablet in healthy females and quantified the amount of etonogestrel and IS.

Conclusion: The developed method for etonogestrel in human plasma has been validated and used in pharmacokinetic studies. 


Keywords


Etonogestrel, human plasma, liquid–liquid extraction, LC–MS/MS, Pharmacokinetics

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References


Milsom I, T Korver. Ovulation incidence with oral contraceptives: a literature review. J Fam Plann Reprod Health Care 2008;34:237-46.

Makarainen L, Van Beek A, Tuomivaara L, Asplund B, Bennink HC. Ovarian function during the use of a single contraceptive implant; Implanon compared with Norplant. Fertil Steril 1998; 69:714–21.

Timmer CJ, TM Mulders. Pharmacokinetics of etonogestrel and ethinylestradiol released from a combined contraceptive vaginal ring. TMT Clin Pharmacokinet 2000;39:233-42.

Timmer CJ, Srivastava N, Dieben TO, Cohen AF. Bioavailability and bioequivalence of etenogestrel from two oral formulations of desogestrel: Cerazette and Liseta. Eur J Metab Pharmacokinet 1999;24:335-43.

Thomas T, Petrie K, Shim J, Abildskov KM, Westhoff CL, Cremers S. A UPLC-MS-MS method for therapeutic drug monitoring of etonogestrel. Ther Drug Monit 2013;35:10.

Liu XF, Ding CG, Ge QH, Zhou Z, Zhi XJ. Simultaneous determination of gestodene, etonogestrel and ethinylestradiol in plasma by LC-MS/MS following derivatization. Yao Xue Xue Bao 2010;45:87-92.

Irving Institute for clinical and translational research. Available from: http://irvinginstitute.columbia.edu/resources/assays/ etonogestrel.html. [Last accessed on 20 Jul 2016]

Pena MA, Sanz E, Francisco S, Alonso A, Abajo Z, Felipe I, et al. Randomized, crossover and single-dose bioequivalence study of two oral desogestrel formulations (film-coated tablets of 75 µg) in healthy female volunteers. Sci Pharm 2012;80:419-31.

Moser C, Zoderer D, Luef G, Rauchenzauner M, Wildt L, Griesmacher A, et al. Simultaneous online SPE-LC-MS/MS quantification of six widely used synthetic progestins in human plasma. Anal Bioanal Chem 2012;403:961-72.

Bleeker JS, WJ Hogan. Thrombocytosis: diagnostic evaluation, thrombotic Risk stratification, and risk-based management strategies. Thrombosis 2011;1-16. http://dx.doi.org/10.1155/ 2011/536062

Castro AD, Concheiro M, Shakleya DM, Huestis MA. Simultaneous quantification of methadone, cocaine, opiates, and metabolites in human placenta by liquid chromatography-mass spectrometry. J Anal Toxicol 2009;33:243–52.

US DHHS FDA CDER. Guidance for Industry: Bioanalytical Method Validation US Department of Health and Human Services Food and Drug Administration Center for Drug Evaluation and Research CDER Center for Veterinary Medicine CV; 2001.

De Boer T, J Wieling. Incurred sample accuracy assessment: design of experiments based on standard addition. Bioanalysis 2011;3:983–92.

Matta MK, Pilli NR, Inamadugu JK, Burugula L, Rao JVLNS. Simultaneous quantification of lamivudine, zidovudine and nevirapine in human plasma by liquid chromatography-tandem mass spectrometry and its application to a pharmacokinetic study. Acta Pharm Sin B 2012;2:472-80.

Matta MK, Pilli NR, Rao JVLNS. A validated liquid chromatography and tandem mass spectrometric method for simultaneous quantitation of tenofovir, emtricitabine and efavirenz in human plasma and its pharmacokinetic application. Acta Chromatographica 2015;27:27-39.

Matta MK, Pilli NR, Rao JVLNS. Bioanalysis of raltegravir, an integrase inhibitor in human plasma by novel SPE–ESI–LC–MS/MS method and its pharmacokinetic application. Am J PharmaTech Res 2013;3:575-86.

Dalia Zidan, Omnia A Ismaiel, Wafaa S Hassan, Abdalla Shalaby. Rapid and validated HPLC-UV method for determination of gemifloxacin in human urine. Int J Pharm Pharm Sci 2015;7:104-8.

ICH Q2B Validation of Analytical Procedures: Methodology. International Conference on Harmonisation, IFPMA, Geneva; 1996.

Athavia BA, Dedania ZR, Dedania RR, Vijayendra Swamy SM, Prajapati CB. Stability indicating HPLC method for determination of vilazodone hydrochloride. Int J Curr Pharm Res 2017;9:123-9.

Comparative LC-MS Stability Indicating Assays of Ondansetron Hydrochloride/Naloxone Hydrochloride and Metoclopramide Hydrochloride/Naloxone Hydrochloride Used In Palliative Care; 2015.

US Department of Health and Human Services, Food and Drug Administration; 2001. Available from: http:// www.fda.gov/cder/guidance/4252fnl.htm. [Last accessed on 25 Jun 2017].




About this article

Title

ESTIMATION OF ETONOGESTREL IN HUMAN PLASMA BY USING LC–ESI–MS/MS METHOD

Keywords

Etonogestrel, human plasma, liquid–liquid extraction, LC–MS/MS, Pharmacokinetics

DOI

10.22159/ijpps.2017v9i12.20946

Date

01-12-2017

Additional Links

Manuscript Submission

Journal

International Journal of Pharmacy and Pharmaceutical Sciences
Vol 9, Issue 12, 2017 Page: 147-154

Online ISSN

0975-1491

Statistics

39 Views | 6 Downloads

Authors & Affiliations

Satish Ramanatham Velamakanni
Bioanalytical lab, Vimta Labs Limited, Cherlapally, Hyderabad 500051, India
India

Venkateswarlu Padala
University College of Chemistry, Jawaharlal Nehru Technological University, Kukatpally, Hyderabad 500085, India
India


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