Determination of Venlafaxine in Bulk and Pharmaceutical Formulations Using Stability Indicating RP-HPLC Method with UV Detector

Author(s): Satish S. Reddi, Gautam Singhvi*, Archana Khosa, Kowthavarapu V. Krishna, Ranendra N. Saha

Journal Name: Current Pharmaceutical Analysis

Volume 15 , Issue 3 , 2019

Become EABM
Become Reviewer
Call for Editor

Graphical Abstract:


Background: A robust and validated analytical method is a key component at various stages of pharmaceutical product development to ensure identity, purity and quality of drugs and formulations.

Objective: The aim of proposed work was to develop and validate a simple, sensitive and stability indicating high performance liquid chromatographic method for the estimation of venlafaxine hydrochloride in bulk and formulations for routine analysis as well as for preformulation studies.

Methods: Efficient chromatographic separation has been performed on a HpyercloneTM 5µm BDS C18 column using a mobile phase consisting of a mixture of phosphate buffer (25 mM, pH 3.0) and acetonitrile (70:30 v/v) at a flow rate of 1 ml min-1. Venlafaxine hydrochloride was analyzed using UV detector at 225nm. Developed method was validated as per ICH guidelines.

Results: The method has demonstrated linearity over the range of 100 to 2000 ng ml-1 with regression equation, mean peak area (y) = 93.32 x concentration - 322.00 (R2 = 1). The method has demonstrated good and consistent recovery (99.34 to 101.16%). Precision of the method reflected by the relative standard deviation values at intra-day and inter-day levels was less than 1.79%. The detection and quantitation limits were 6.55 ng ml-1 and 19.84 ng ml-1 respectively indicating sensitivity of the method. The method was successfully applied for the estimation of venlafaxine hydrochloride in marketed and inhouse formulations. Also, developed method was successfully used in drug-excipients compatibility studies for VEN.

Conclusion: The method was found to be accurate, precise, sensitive and selective for the determination venlafaxine hydrochloride in bulk and pharmaceutical formulations.

Keywords: Venlafaxine, stability indicating, high performance liquid chromatography, analytical method, validation. drugexcipient compatibility.

Chidambaram, M.; Krishnasamy, K. Drug-drug/drug-excipient compatibility studies on curcumin using non-thermal methods. Adv. Pharm. Bull., 2014, 4(3), 309-312.
Balestrieri, F.; Magrì, A.D.; Magrì, A.L.; Marini, D.; Sacchini, A. Application of differential scanning colorimetry to the study of drug-excipient compatibility. Thermochim. Acta, 1996, 285(2), 337-345.
Rozet, E.; Ceccato, A.; Hubert, C.; Ziemons, E.; Oprean, R.
Rudaz, S.; Boulanger, B.; Hubert, P. Analysis of recent pharmaceutical regulatory documents on analytical method validation. J. Chromatogr. A, 2007, 1158, 111-125.
Alsante, K.M.; Ando, A.; Brown, R.; Ensing, J.; Hatajik, T.D.; Kong, W.; Tsuda, Y. The role of degradant profiling in active pharmaceutical ingredients and drug products. Adv. Drug Deliver. Rev., 2007, 59, 29-37.
Bakshi, M.; Singh, S. Development of validated stability-indicating assay methods -critical review. J. Pharm. Biomed. Anal., 2002, 28, 1011-1040.
Gutierrez, M.A.; Stimmel, G.L.; Aiso, J.Y. Venlafaxine: a 2003 update. Clin. Ther., 2003, 25, 2138-2154.
Rudaz, S.; Stella, C.; Balant-Gorgia, A.E.; Fanali, S.; Veuthey, J.L. Simultaneous stereoselective analysis of venlafaxine and O-desmethylvenlafaxine enantiomers in clinical samples by capillary electrophoresis using charged cyclodextrins. J. Pharm. Biomed. Anal., 2000, 23, 107-115.
Rudaz, S.; Veuthey, J.L.; Desiderio, C.; Fanali, S. Enantioseparation of venlafaxine and O-desmethylvenlafaxine by capillary electrophoresis with mixed cyclodextrins. Chromatographia, 1999, 50, 369-372.
Vu, R.L.; Helmeste, D.; Albers, L.; Reist, C. Rapid determination of venlafaxine and O-desmethylvenlafaxine in human plasma by high-performance liquid chromatography with fluorimetric detection. J. Chromatogr. B, 1997, 703, 195-201.
Bhatt, J.; Jangid, A.; Venkatesh, G.; Subbaiah, G.; Singh, S. Liquid chromatography-tandem mass spectrometry (LC-MS-MS) method for simultaneous determination of venlafaxine and its active metabolite O-desmethylvenlafaxine in human plasma. J. Chromatogr. B, 2005, 829, 75-81.
Liu, W.; Cai, H.; Li, H. High performance liquid chromatography - electrospray ionization mass spectrometry (HPLC-MS/ESI) method for simultaneous determination of venlafaxine and its three metabolites in human plasma. J. Chromatogr. B, 2007, 850, 405-411.
Patel, B.N.; Sharma, N.; Sanyal, M.; Shrivastav, P.S. Liquid chromatography tandem mass spectrometry assay for the simultaneous determination of venlafaxine and O-desmethylvenlafaxine in human plasma and its application to a bioequivalence study. J. Pharm. Biomed. Anal., 2008, 47, 603-611.
Makhija, S.N.; Vavia, P.R. Stability indicating LC method for the estimation of venlafaxine in pharmaceutical formulations. J. Pharm. Biomed. Anal., 2002, 28, 1055-1059.
Rao, R.N.; Raju, A.N. Simultaneous separation and determination of process-related substances and degradation products of venlafaxine by reversed-phase HPLC. J. Sep. Sci., 2006, 29, 2733-2744.
Chhalotiya, U.K.; Patel, H.B.; Bhatt, K.K. Development and validation of an ultra-performance liquid chromatography method for venlafaxine hydrochloride in bulk and capsule dosage form. Indian J. Pharm. Sci., 2010, 72(6), 814-818.
Baldania, S.L.; Bhatt, K.K.; Mehta, R.S.; Shah, D.A.; Gandhi, T.R. RP-HPLC estimation of venlafaxine hydrochloride in tablet dosage forms. Indian J. Pharm. Sci., 2008, 70(1), 124-128.
Asafu-Adjaye, E.B.; Faustino, P.J.; Tawakkul, M.A.; Anderson, L.W.; Lawrence, X.Y.; Kwon, H.; Volpe, D.A. Validation and application of a stability-indicating HPLC method for the in vitro determination of gastric and intestinal stability of venlafaxine. J. Pharm. Biomed. Anal., 2007, 43(5), 1854-1859.
ICH Q2(R1) guideline - Validation of analytical procedures: text and methodology. ICH_Products/Guidelines/Quality/Q2_R1/Step4/Q2_R1__Guideline.pdf (Accessed on: August 16, 2016)
Singhvi, G.; Gampa, G.; Saha, R.N. Development and validation of a stability indicating liquid chromatographic method for the determination of milnacipran in bulk and its formulations. Curr. Pharm. Anal., 2013, 9(2), 191-198.
Singhvi, G.; Kumar, V.; Ukawala, R.; Saha, R.N. Development of bioanalytical hplc method for estimation of milnacipran hydrochloride in rabbit plasma using solid phase extraction technique and its application in pharmacokinetic investigation. Curr. Pharm. Anal., 2017, 6, 574-580.
Bolton, S. Pharmaceutical statistics: practical and clinical applications. 3rd ed. New York: Marcel Dekker, 199.
Verma, R.K.; Garg, S. Compatibility studies between isosorbide mononitrate and selected excipients used in the development of extended release formulations. J. Pharm. Biomed. Anal., 2004, 35, 449-458.
McDaid, F.M.; Barker, S.A.; Fitzpatrick, S.; Petts, C.R.; Craig, D.Q.M. Further investigations into the use of high sensitivity differential scanning calorimetry as a means of predicting drug-excipient interactions. Int. J. Pharm., 2003, 252, 235-240.
Balestrieri, F.; Magri, A.D.; Magri, A.L.; Marini, D.; Sacchini, A. Application of differential scanning calorimetry to the study of drug-excipient compatibility. Thermochim. Acta, 1996, 285, 337-345.
Schmitt, E.A.; Peck, K.; Sun, Y.; Geoffroy, J.M. Rapid, practical and predictive excipient compatibility screening using isothermal microcalorimetry. Thermochim. Acta, 2001, 380, 175-183.
Pani, N.R.; Nath, L.K.; Acharya, S.; Bhuniya, B. Application of DSC, IST, and FTIR study in the compatibility testing of nateglinide with different pharmaceutical excipients. J. Therm. Anal. Calorim., 2012, 108, 219-226.
Pharmaceutical development report - example QbD for IR generic drugs; The United States Food and Drug Administration: Maryland, USA, 2012, pp. 25-28.

Rights & PermissionsPrintExport Cite as

Article Details

Year: 2019
Published on: 11 February, 2019
Page: [258 - 265]
Pages: 8
DOI: 10.2174/1573412914666171228162205
Price: $65

Article Metrics

PDF: 34
PRC: 1