A Systematic Review on Analytical Methods to Determine Chiral and Achiral Forms of Venlafaxine and its Metabolite O-desmethylvenlafaxine

Author(s): Sunil K. Dubey*, Monika Jindal, Shakti Nagpal, Ranendra N. Saha, Gautam Singhvi*, Amit Anand, Kowthavarapu V. Krishna

Journal Name: Current Pharmaceutical Analysis

Volume 16 , Issue 5 , 2020


Become EABM
Become Reviewer
Call for Editor

Graphical Abstract:


Abstract:

Background: Venlafaxine (VEN) is a bicyclic phenylethylamine derivative and possesses a marked structural difference from other antidepressant drugs present in the market. It works by eliciting the neurotransmitter action in CNS. It occurs in two enantiomeric forms i.e. R and S VEN. After the first pass metabolism, it gets metabolized into more active form O-desmethylvenlafaxine (ODV) which also exist in the enantiomeric forms. So it is important to develop a suitable analytical and bioanalytical method for the determination of VEN and its metabolite to quantify them accurately.

Methods and Results: The current review summarizes methods to determine chiral and achiral forms of VEN and ODV. According to the literature, it is clear that most widely used method for the determination of VEN and ODV is liquid chromatography-mass spectroscopy, other methods used for routine analysis include UV spectroscopy, reverse phase high-performance liquid chromatography with PDA detector. For the determination of enantiomeric forms of VEN and ODV, different chiral columns have been utilized. Capillary electrophoresis with charged cyclodextrins is also used to determine the enantiomeric forms.

Conclusion: Various analytical methods for determining VEN and its metabolite in different matrices have been discussed thoroughly in the present review.

Keywords: Venlafaxine, O-desmethylvenlafaxine, stereoselective, HPLC, LC-MS/MS, spectrophotometry.

[1]
Rang, H.; Dale, M.; Ritter, J.; Flower, R. Rang & Dale’s Pharmacology, (6th ed.); , 2007, pp. 457-459.
[2]
Bhowmik, D.; Sampath Kumar, K.P.; Srivastava, S.; Paswan, S.; Dutta, A.S. Depression - Symptoms, Causes, Medications and Therapies. Pharm. Innov., 2012, 1(3), 37-51.
[3]
Liu, Y.; Sun, Y.; Sun, J.; Zhao, N.; Sun, M.; He, Z. Preparation and in vitro/in vivo evaluation of sustained-release venlafaxine hydrochloride pellets. Int. J. Pharm., 2012, 426(1-2), 21-28.
[http://dx.doi.org/10.1016/j.ijpharm.2011.12.053] [PMID: 22266529]
[4]
Whittington, C.J.; Kendall, T.; Fonagy, P.; Cottrell, D.; Cotgrove, A.; Boddington, E. Selective serotonin reuptake inhibitors in childhood depression: systematic review of published versus unpublished data. Lancet, 2004, 363(9418), 1314-1345.
[http://dx.doi.org/10.1016/S0140-6736(04)16043-1]
[5]
Verdu, B.; Decosterd, I.; Buclin, T.; Stiefel, F.; Berney, A. Antidepressants for the treatment of chronic pain. Drugs, 2008, 68(18), 2611-2632.
[http://dx.doi.org/10.2165/0003495-200868180-00007] [PMID: 19093703]
[6]
Rudorfer, M.V.; Potter, W.Z. The Role of Metabolites of Antidepressants in the Treatment of Depression. CNS Drugs, 1997, 7(4), 273-312.
[http://dx.doi.org/10.2165/00023210-199707040-00003] [PMID: 27520753]
[7]
Biglia, N.; Torta, R.; Roagna, R.; Maggiorotto, F.; Cacciari, F.; Ponzone, R.; Kubatzki, F.; Sismondi, P. Evaluation of low-dose venlafaxine hydrochloride for the therapy of hot flushes in breast cancer survivors. Maturitas, 2005, 52(1), 78-85.
[http://dx.doi.org/10.1016/j.maturitas.2005.01.001] [PMID: 16143229]
[8]
Sheorey, S.D.; Vachhani, U.D.; Vaghani, S.S.; Pandya, A.; Soni, H.; Shah, S. Analytical Method Validation for the Determination and Quantification of Venlafaxine Hydrochloride and Its Stress Degradation Studies. Int. J. Pharm. Chem. Sci., 2012, 1(4), 1951-1959.
[9]
Karani, A.; Pingale, P. Analytical method development & validation of venlafaxine hydrochloride in solid dosage forms using uv spectrophotometer. J. Pharm. Res., 2009, 2(7), 1246-1249.
[10]
Sowmya, C.; Reddy, Y.P.; Kumar, K.M.; Raja, S.M. Development and validation of spectrophotometric method for the estimation of venlafaxine in bulk and formulations. Int. J. Chem. Sci., 2011, 1(9), 52-58.
[11]
Shahnawaz, S.; Siddiqui, Z.; Hoda, Q. Sensitive spectrofluorimetric method of analysis for venlafaxine in spiked rat plasma and formulations. J. Fluoresc., 2010, 20(4), 821-825.
[http://dx.doi.org/10.1007/s10895-010-0624-2] [PMID: 20191378]
[12]
Raghubabu, K.; Swarup, L.S.; Kalyanaramu, B.; Rao, M.N. Simple and Inexpensive Methods Development for Determination of Venlafaxine Hydrochloride from Its Solid Dosage Forms by Visible Spectrophotometry. J. Chem., 2012, 9(3), 1645-1654.
[13]
Ardeshna, H.H.; Moradiya, R.M.; Shah, A.P.; Nakrani, S.R.; Patel, G.K.; Gandhi, R.T. Spectroflourimetric determination of venlafaxine hydrochloride and odesmethylvenlafaxine. Pharma Chem., 2012, 4(5), 1956-1961.
[14]
Lavanya, K.; Sunitha, P.; Kumar, A.A.; Ramana, K.V. New simple UV spectrophotometric method for determination of Venlafaxine hydrochloride in Bulk and pharmaceutical dosage forms. Int. J. Pharmaceut. Qual. Assurance, 2013, 4(1), 1-3.
[15]
Du, L. Wei; Lei; Wang; Gong, Q.; Wang, A fluorescence method for the determination of venlafaxine hydrochloride. J. Anal. Methods, 2014, 6(4), 1108-1113.
[http://dx.doi.org/10.1039/C3AY41694A]
[16]
Eswarudu, M.M.; Anitha, V.; Babu, P.S. New simple UV spectrophotometric method for determination of venlafaxine hydrochloride in pure and pharmaceutical formulation. J. Pharm. Pharm. Sci., 2017, 6(7), 1292-1300.
[17]
Edla, S.a. A novel RP-HPLC method for the determination of venlafaxine in pharmaceutical drug products. Int. J. Sci. Tec., 2012, 1(1), 11-21.
[18]
Rosado, T.; Gonçalves, A.; Martinho, A.; Alves, G.; Duarte, A.P.; Domingues, F.; Silvestre, S.; Granadeiro, B.; Oliveira, V.; Leitão, C.; Gallardo, E. Simultaneous Quantification of Antidepressants and Metabolites in Urine and Plasma Samples by GC–MS for Therapeutic Drug Monitoring. J. Chromatographia., 2017, 80(2), 301-328.
[http://dx.doi.org/10.1007/s10337-017-3240-3]
[19]
Pan, P.P.; Wang, S.H.; Wang, J.; Luo, J.; Geng, P.W.; Zhou, Y.F.; Hu, G.X. Simultaneous Determination of Methadone, Fluoxetine, Venlafaxine and Their Metabolites in Rat Plasma by UPLC–MS/MS for Drug Interaction Study. J. Chromatographia, 2016, 78(9-10), 601-608.
[http://dx.doi.org/10.1007/s10337-016-3062-8]
[20]
Rao, K.B.; Manjula, R.K.; Babu, S.K.; Rambabu, C. Validation of stability indicating RP-HPLC method for the assay of venlafaxine in pharmaceutical dosage form. Scholars Res. Lib., 2015, 7(3), 247-256.
[21]
Berm, E.J.; Brummel-Mulder, E.; Paardekooper, J.; Hak, E.; Wilffert, B.; Maring, J.G. Determination of venlafaxine and O-desmethylvenlafaxine in dried blood spots for TDM purposes, using LC-MS/MS. Anal. Bioanal. Chem., 2014, 406(9-10), 2349-2353.
[http://dx.doi.org/10.1007/s00216-014-7619-9] [PMID: 24493333]
[22]
Kang, H.K.; Kang, M.A.; Kim, H.J.; Park, Y.S.; Kim, Y.S.; Kang, J.S. Development of a LC-MS/MS for Quantification of Venlafaxine in Human Plasma and Application to Bioequivalence Study in healthy Korean Subjects. Transl. Clin. Pharmacol., 2014, 22(1), 35-42.
[http://dx.doi.org/10.12793/tcp.2014.22.1.35]
[23]
Magalhães, P.; Alves, G.; Rodrigues, M.; LLerena, A.; Falcão, A. First MEPS/HPLC assay for the simultaneous determination of venlafaxine and O-desmethylvenlafaxine in human plasma. Bioanalysis, 2014, 6(22), 3025-3038.
[http://dx.doi.org/10.4155/bio.14.222] [PMID: 25496255]
[24]
Dubey, N.P.; Agrawal, N.; Kumar, V.; Bose, D. simultaneous determination of venlafaxine, duloxetine, quetiapine,ibuprofen and paracetamol: a case study. Int. J. Chromatogr. Sci., 2014, 4(1), 6-10.
[25]
Reddy, D.C.; Bapuji, A.T.; Rao, V.S.; Himabindu, V.; Ravinder, S. High throughput and sensitive LC-MS/MS method for the estimation of venlafaxine and its active metabolite o-desmethyl venlafaxine in human plasma and its application to a pharmacokinetic study. J. Liq. Chromatogr. Relat. Technol., 2012, 36(7), 897-913.
[http://dx.doi.org/10.1080/10826076.2012.678455]
[26]
Dubey, S.K.; Saha, R.N.; Jangala, H.; Pasha, S. Rapid sensitive validated UPLC-MS method for determination of venlafaxine and its metabolite in rat plasma: Application to pharmacokinetic study. J. Pharm. Anal., 2013, 3(6), 466-471.
[http://dx.doi.org/10.1016/j.jpha.2013.05.002] [PMID: 29403857]
[27]
Uřinovská, R.; Brozmanová, H.; Sištík, P.; Silhán, P.; Kacířová, I.; Lemr, K.; Grundmann, M. Liquid chromatography-tandem mass spectrometry method for determination of five antidepressants and four atypical antipsychotics and their main metabolites in human serum. J. Chromatogr. B Analyt. Technol. Biomed. Life Sci., 2012, 907(1), 101-107.
[http://dx.doi.org/10.1016/j.jchromb.2012.09.009] [PMID: 23026228]
[28]
Moussa, B.A.; El-Bagary, I.R.; Al-Eryani, Y.A. Development and validation of a stability-indicating HPLC method for the analysis of desvenlafaxine succinate in the presence of its acidic induced degradation product in bulk and pharmaceutical preparation. J. Chem. Pharm. Res., 2011, 3(5), 425-437.
[29]
Bokka, R.; Narayana, P.; Reddy, A. Stability-indicating HPTLC method for analysis of venlafaxine hydrochloride, and use of the method to study degradation kinetics. J. Planar Chromatogr. Mod. TLC, 2011, 24(2), 160-165.
[http://dx.doi.org/10.1556/JPC.24.2011.2.15]
[30]
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.
[http://dx.doi.org/10.4103/0250-474X.84605] [PMID: 21969762]
[31]
Ardakani, Y.H.; Foroumadi, A.; Rouini, M.R. Development and validation of a rapid HPLC- fluorescence method for simultaneous determination of venlafaxine and its major metabolites in human plasma. Daru, 2010, 18(2), 97-102.
[PMID: 22615601]
[32]
Qin, F.; Li, N.; Qin, T.; Zhang, Y.; Li, F. Simultaneous quantification of venlafaxine and O-desmethylvenlafaxine in human plasma by ultra performance liquid chromatography-tandem mass spectrometry and its application in a pharmacokinetic study. J. Chromatogr. B Analyt. Technol. Biomed. Life Sci., 2010, 878(7-8), 689-694.
[http://dx.doi.org/10.1016/j.jchromb.2010.01.007] [PMID: 20133212]
[33]
Favretto, D.; Stocchero, G.; Vogliardi, S.; Frison, G.; Trevisanuto, D.; Castagna, F.; Ferrara, S.D. Neonatal hair analysis by liquid chromatography-high-resolution mass spectrometry to reveal gestational exposure to venlafaxine. Ther. Drug Monit., 2010, 32(1), 30-39.
[http://dx.doi.org/10.1097/FTD.0b013e3181c01e16] [PMID: 19855313]
[34]
Rajasekhar, D.; Kumar, I.J.; Venkateswarlu, P. Rapid high-performance liquid chromatography-tandem mass spectrometry method for simultaneous measurement of venlafaxine and O-desmethylvenlafaxine in human plasma and its application in comparative bioavailability study. Biomed. Chromatogr., 2009, 23(12), 1300-1307.
[http://dx.doi.org/10.1002/bmc.1253] [PMID: 19517423]
[35]
Shah, G.R.; Thaker, B.T.; Surati, K.R.; Parabia, M.H. Simultaneous determination of venlafaxine and its main active metabolite O-desmethyl venlafaxine in rat plasma by LC-MS/MS. Anal. Sci., 2009, 25(10), 1207-1210.
[http://dx.doi.org/10.2116/analsci.25.1207] [PMID: 19822964]
[36]
Bernardi, L.S.; Oliveira, P.R.; Murakami, F.S.; Borgmann, S.H.; Arend, M.Z.; Cardoso, S.G. Development and validation of a stability-indicating LC method for the determination of venlafaxine in extended-release capsules and dissolution kinetic studies. J. Chromatogr. Sci., 2009, 47(9), 770-776.
[http://dx.doi.org/10.1093/chromsci/47.9.770] [PMID: 19835686]
[37]
Suenaga, E.M.; Ifa, D.R.; Cruz, A.C.; Pereira, R.; Abib, E.; Tominga, M.; Nakaie, C.R. Automated determination of venlafaxine in human plasma by on-line SPE-LC-MS/MS. Application to a bioequivalence study. J. Sep. Sci., 2009, 32(4), 637-643.
[http://dx.doi.org/10.1002/jssc.200800629] [PMID: 19212975]
[38]
Qin, X.Y.; Meng, J.; Li, X.Y.; Zhou, J.; Sun, X.L.; Wen, A.D. Determination of venlafaxine in human plasma by high-performance liquid chromatography using cloud-point extraction and spectrofluorimetric detection. J. Chromatogr. B Analyt. Technol. Biomed. Life Sci., 2008, 872(1-2), 38-42.
[http://dx.doi.org/10.1016/j.jchromb.2008.06.052] [PMID: 18675598]
[39]
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(3), 603-611.
[http://dx.doi.org/10.1016/j.jpba.2008.02.015] [PMID: 18387768]
[40]
Mandrioli, R.; Mercolini, L.; Cesta, R.; Fanali, S.; Amore, M.; Raggi, M.A. Analysis of the second generation antidepressant venlafaxine and its main active metabolite O-desmethylvenlafaxine in human plasma by HPLC with spectrofluorimetric detection. J. Chromatogr. B Analyt. Technol. Biomed. Life Sci., 2007, 856(1-2), 88-94.
[http://dx.doi.org/10.1016/j.jchromb.2007.05.046] [PMID: 17581798]
[41]
Wei, Z.; Bing-Ren, X.; Cai-Yun, W. Liquid chromatography-mass spectrometry method for the determination of venlafaxine in human plasma and application to a pharmacokinetic study. Biomed. Chromatogr., 2007, 21(3), 266-272.
[http://dx.doi.org/10.1002/bmc.748] [PMID: 17230450]
[42]
Nageswara Rao, R.; Narasa Raju, A. Simultaneous separation and determination of process-related substances and degradation products of venlafaxine by reversed-phase HPLC. J. Sep. Sci., 2006, 29(18), 2733-2744.
[http://dx.doi.org/10.1002/jssc.200600225] [PMID: 17305234]
[43]
Dubey, S.K.; Anand, A.; Saha, R.N. Stability indicating high performance thin layer chromatographic method for quantitation of venlafaxine in bulk and pharmaceutical dosage form. Drug Dev. Therap., 2015, 6(1), 33.
[http://dx.doi.org/10.4103/2394-2002.148891]
[44]
Matoga, M.; Pehourcq, F.; Titier, K.; Dumora, F.; Jarry, C. Rapid high-performance liquid chromatographic measurement of venlafaxine and O-desmethylvenlafaxine in human plasma. Application to management of acute intoxications. J. Chromatogr. B Biomed. Sci. Appl., 2001, 760(2), 213-218.
[http://dx.doi.org/10.1016/S0378-4347(01)00270-5] [PMID: 11530979]
[45]
Frahnert, C.; Rao, M.L.; Grasmäder, K. Analysis of eighteen antidepressants, four atypical antipsychotics and active metabolites in serum by liquid chromatography: a simple tool for therapeutic drug monitoring. J. Chromatogr. B Analyt. Technol. Biomed. Life Sci., 2003, 794(1), 35-47.
[http://dx.doi.org/10.1016/S1570-0232(03)00393-3] [PMID: 12888196]
[46]
Hicks, D.R.; Wolaniuk, D.; Russell, A.; Cavanaugh, N.; Kraml, M. A high-performance liquid chromatographic method for the simultaneous determination of venlafaxine and O-desmethylvenlafaxine in biological fluids. Ther. Drug Monit., 1994, 16(1), 100-107.
[http://dx.doi.org/10.1097/00007691-199402000-00016] [PMID: 8160247]
[47]
Wille, S.M.; De Letter, E.A.; Piette, M.H.; Van Overschelde, L.K.; Van Peteghem, C.H.; Lambert, W.E. Determination of antidepressants in human postmortem blood, brain tissue, and hair using gas chromatography-mass spectrometry. Int. J. Legal Med., 2009, 123(6), 451-458.
[http://dx.doi.org/10.1007/s00414-008-0287-6] [PMID: 18839201]
[48]
Ahmad Panahi, H.; Alaei, H.S. β-Cyclodextrin/thermosensitive containing polymer brushes grafted onto magnetite nano-particles for extraction and determination of venlafaxine in biological and pharmaceutical samples. Int. J. Pharm., 2014, 476(1-2), 178-184.
[http://dx.doi.org/10.1016/j.ijpharm.2014.09.051] [PMID: 25278039]
[49]
Dziurkowska, E.; Wesolowski, M. Simultaneous quantitation of venlafaxine and its main metabolite, O-desmethylvenlafaxine, in human saliva by HPLC. J. Sep. Sci., 2013, 36(11), 1726-1733.
[http://dx.doi.org/10.1002/jssc.201300087] [PMID: 23495235]
[50]
Madrakian, T.; Haryani, R.; Ahmadi, M.; Afkhami, A. A sensitive electrochemical sensor for rapid and selective determination of venlafaxine in biological fluids using carbon paste electrode modified with molecularly imprinted polymer-coated magnetite nanoparticles. J. Iran. Chemical Soc., 2016, 13(2), 243-251.
[http://dx.doi.org/10.1007/s13738-015-0731-8]
[51]
J, H. A.; Lawati, A. I.; Varma, G. B.; Suliman, F. E. O. High-throughput method for the analysis of venlafaxine in pharmaceutical formulations and biological fluids, using a tris(2,2′-bipyridyl) ruthenium(II)–peroxydisulphate chemiluminescence system in a two-chip device. J. Biol. Chemical Lumin., 2013, 28(1), 44-49.
[52]
Dziurkowska, E.; Wesolowski, M.; Dziurkowski, M. Salivary cortisol in women with major depressive disorder under selective serotonin reuptake inhibitors therapy. Arch. Women Ment. Health, 2013, 16(2), 139-147.
[http://dx.doi.org/10.1007/s00737-013-0329-z] [PMID: 23371518]
[53]
Al-bedair. Lamia A. Determination of venlafaxine hydrochloride in biological fluids using prepared ion selective electrode. Int. J. Pharma Sci., 2016, 37(2), 244-248.
[54]
Al-bedair. Lamia A. Ion-selective electrode determination of venlafaxine hydrochloride in pure form and capsules. Env. Pharmacol. Life Sci, 2016, 5(6), 48-52.
[55]
Ding, L.; Li, L.; You, W.; Gao, Z.; Yanga, T. Electrocatalytic oxidation of venlafaxine at a multiwall carbon nanotubes-ionic liquid gel modified glassy carbon electrode and its electrochemical determination. Croat. Chem. Acta, 2015, 88(1), 81-87.
[http://dx.doi.org/10.5562/cca2420]
[56]
Morais, S.; Ryckaert, C.; Delerue-Matos, C. Adsorptive stripping voltammetric determination of venlafaxine in urine with a mercury film microelectrode. Anal. Lett., 2013, 36(11), 2515-2526.
[http://dx.doi.org/10.1081/AL-120024339]
[57]
Sanghavi, B.J.; Srivastava, A.K. Adsorptive stripping differential pulse voltammetric determination of venlafaxine and desvenlafaxine employing Nafion–carbon nanotube composite glassy carbon electrode. Electrochim. Acta, 2011, 56, 4188-4196.
[http://dx.doi.org/10.1016/j.electacta.2011.01.097]
[58]
Chen, J.W.; Duan, C.Q.; Gao, Z.N. Electrocatalytic oxidation and electrochemical determination of venlafaxine at acetylene black-ionic liquid modified glassy carbon electrode. Yaowu Fenxi Zazhi, 2012, 32(3), 515-519.
[59]
Lima, J.L.; Loo, D.V.; Delerue-Matos, C.; da Silva, A.S. Electrochemical behaviour of Venlafaxine and its determination in pharmaceutical products using square wave voltammetry. Farmaco, 1999, 54(3), 145-148.
[http://dx.doi.org/10.1016/S0014-827X(99)00007-5] [PMID: 10371026]
[60]
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(1), 107-115.
[http://dx.doi.org/10.1016/S0731-7085(00)00280-6] [PMID: 10898160]
[61]
Fanali, S.; Rudaz, S.; Veuthey, J.L.; Desiderio, C. Use of vancomycin silica stationary phase in packed capillary electrochromatography. II. Enantiomer separation of venlafaxine and O-desmethylvenlafaxine in human plasma. J. Chromatogr. A, 2001, 919(1), 195-203.
[http://dx.doi.org/10.1016/S0021-9673(01)00781-6] [PMID: 11459304]
[62]
Kingbäck, M.; Josefsson, M.; Karlsson, L.; Ahlner, J.; Bengtsson, F.; Kugelberg, F.C.; Carlsson, B. Stereoselective determination of venlafaxine and its three demethylated metabolites in human plasma and whole blood by liquid chromatography with electrospray tandem mass spectrometric detection and solid phase extraction. J. Pharm. Biomed. Anal., 2010, 53(3), 583-590.
[http://dx.doi.org/10.1016/j.jpba.2010.03.043] [PMID: 20435422]
[63]
Liu, W.; Wang, F.; Li, H.D.; Wang, F. Simultaneous stereoselective analysis of venlafaxine and O-desmethylvenlafaxine enantiomers in human plasma by HPLC-ESI/MS using a vancomycin chiral column. J. Chromatogr. B Analyt. Technol. Biomed. Life Sci., 2007, 850(1-2), 183-189.
[http://dx.doi.org/10.1016/j.jchromb.2006.11.021] [PMID: 17140867]
[64]
Dubey, S.K.; Anand, A.; Saha, R.N. Enantioselective disposition of venlafaxine and its metabolite o-desmethylvenlafaxine in rats. Int. J., 2017, 2(1), 39-45.
[65]
Kingbäck, M.; Karlsson, L.; Zackrisson, A.L.; Carlsson, B.; Josefsson, M.; Bengtsson, F.; Ahlner, J.; Kugelberg, F.C. Influence of CYP2D6 genotype on the disposition of the enantiomers of venlafaxine and its major metabolites in postmortem femoral blood. Forensic Sci. Int., 2012, 214(1-3), 124-134.
[http://dx.doi.org/10.1016/j.forsciint.2011.07.034] [PMID: 21840145]


Rights & PermissionsPrintExport Cite as

Article Details

VOLUME: 16
ISSUE: 5
Year: 2020
Published on: 15 June, 2020
Page: [474 - 486]
Pages: 13
DOI: 10.2174/1573412915666190204144202
Price: $65

Article Metrics

PDF: 19
HTML: 2