ANTIVIRAL DRUGS FOR INFLUENZA VIRUSES
Keywords:Antiviral Drugs, Influenza Viruses, Oseltamivir, Laninamivir, Zanamivir, Peramivir, Metabolite, HPLC, UPLC, LCMS
Antiviral drugs have significant action against influenza viruses A and B. Virus spread deadly disease in which many people die, and the country economy greatly suffer. Presently, most of the people need to get vaccination, which is depending on the dose limit in humans. It reacts directly or sometimes indirectly in the form of metabolites. However, it is mandatory to know how much drug is absorbed or metabolites concentration after administered. Therefore, pharmacokinetics data is very crucial for all drugs. Our review discusses the mechanism of drugs action and their activity and also describes how antiviral drugs and their metabolites is determined using a highly sensitive instrument such as high-performance liquid chromatography (HPLC), ultra-pressure liquid chromatography (UPLC), mass spectrometry (MS). Therefore, the present review gives brief information about antiviral drugs, their activity, biotransformation and analytical methods for quantification and this information will be helpful for any future studies done by experts in this field and will be beneficial for research scientists and influenza experts of all over the globe.
Zhu HY, Han L, Shi XL, Wang BL, Huang H, Wang X, et al. Baicalin inhibits autophagy induced by influenza a virus H3N2. Antiviral Res 2015;113:62-70.
Fiore AE, Shay DK, Broder K, Iskander JK, Uyeki TM, Mootrey G, et al. Centers for disease control and prevention (CDC), advisory committee on immunization practices (ACIP). Prevention and control of influenza: recommendations of the advisory committee on immunization practices (ACIP). MMWR Recomm Rep 2008;57(RR-7):1–60.
Chang SC, Cheng YY, Shih SR. Avian influenza virus: the threat of a pandemic. Chang Gung Med J 2006;29:130–4.
Liu Y, Zhang J, Xu W. Recent progress in rational drug design of neuraminidase inhibitors. Curr Med Chem 2007;14:2872–91.
Zhang Z. Spatio-temporal data comparisons for global highly pathogenic avian influenza (HPAI) H5N1 outbreaks. PLoS One 2010;5:e15314.
Tanaka T. Safety of neuraminidase inhibitors against novel influenza A (H1N1) in pregnant and breastfeeding women. Can Med Assoc J 2009;181:55–8.
Laver WG, Bischofberger N, Webster RG. Disarming flu viruses. Sci Am 1999;280:78–87.
Laver WG, Bischofberger N, Webster RG. The origin and control of pandemic influenza. Perspect Biol Med 2000;43:173–92.
Palese P, Schulman JL, Bodo G, Meindl P. Inhibition of influenza and parainfluenza virus replication in tissue culture by 2-deoxy-2,3-dehydro-N-trifluoro-acetylneuraminic acid (FANA). Virology 1974;59:490–8.
Russell RJ. The structure of H5N1 avian influenza neuraminidase suggests new opportunities for drug design. Nature 2006;443:45–9.
Pinto LH, Holsinger LJ, Lamb RA. Influenza virus M2 protein has ion channel activity. Cell 1992;69:517–28.
Hayden FG. Amantadine and rimantadine-clinical aspects. In: Richman DD. editor. Antiviral Drug Resistance. New York: John Wiley and Sons, Inc; 1996. p. 59-77.
Hay AJ, Wolstenholme AJ, Skehel JJ. The molecular basis of the specific anti-influenza action of amantadine. The EMBO J 1985;4:3021–4.
Sidwell RW, Huffman JH, Barnard DL. Inhibition of influenza virus infections in mice by GS4104, an orally effective influenza virus neuraminidase inhibitor. Antiviral Res 1998;37:107–20.
Monto AS, Fleming DM, Henry D. Efficacy and safety of the neuraminidase inhibitor zanamivirin the treatment of influenza A and B virus infections. J Infect Dis 1999;180:254–61.
Monto AS. The role of antivirals in the control of influenza. Vaccine 2003;21:1796–800.
McKimm BJL. Management of influenza virus infections with neuraminidase inhibitors: detection, incidence, and implications of drug resistance. Treat Respir Med 2005;4:107–16.
Wade RC. Flu and structure-based drug design. Structure 1997;5:1139–45.
Gubareva LV, Kaiser L, Hayden FG. Influenza virus neuraminidase inhibitors. Lancet 2000;355:827–35.
Laver WG. From the great barrier reef to a "Cure" for the flu: tall tales, but true. Perspect Biol Med 2004;47:590–6.
Muthuri SG. Effectiveness of neuraminidase inhibitors in reducing mortality in patients admitted to hospital with influenza A H1N1pdm09 virus infection: a meta-analysis of individual participant data. Lancet Resp Med 2014;2:395–404.
Heneghan CJ. Neuraminidase inhibitors for influenza: a systematic review and meta-analysis of regulatory and mortality data. Health Technol Assess 2016;20:1-242.
Luo M. Structural biology: antiviral drugs fit for a purpose. Nature 2006;443:37–38.
McLaughlin MM, Skoglund EW, Ison MG. Peramivir: an intravenous neuraminidase inhibitor. Expert Opin Pharmacother 2015;16:1889–900.
Yamashita M. CS-8958, a prodrug of the new neuraminidase inhibitor R-125489, shows long-acting anti-influenza virus activity. Antimicrob Agents Chemother 2009;53:186–92.
Burger RA. Immunological effects of the orally administered neuraminidase inhibitor oseltamivir in influenza virus-infected and uninfected mice. Immun Pharma 2000;47:45–52.
Klumpp K, Graves BJ. Optimization of small molecule drugs binding to highly polar target sites: lessons from the discovery and development of neuraminidase inhibitors. Curr Top Med Chem 2006;6:423–34.
Vavricka CJ. Structural and functional analysis of laninamivir and its octanoate prodrug reveals group specific mechanisms for influenza NA inhibition. PLoS Pathog 2011;7:e1002249.
Bright RA, Medina MJ, Xu X, Perez Oronoz G, Wallis TR. Incidence of adamantane resistance among influenza A (H3N2) viruses isolated worldwide from 1994 to 2005: a cause for concern. Lancet 2005;366:1175–81.
Bright RA, Shay DK, Shu B, Cox NJ, Klimov A. Adamantane resistance among influenza viruses isolated early during the 2005–2006 influenza season in the United States. JAMA: J Am Med Assoc 2006;295:891–4.
Duque MD, Valverde E, Barniol M, Guardiola S, Rey M. Inhibitors of the M2 channel of influenza a virus. Recent Adv Pharm Sci 2011;2:35–64.
Govorkova EA, McCullers JA. Therapeutics against influenza. Curr Top Microbiol Immunol 2013;370:273–300.
Helenius A. Unpacking the incoming influenza virus. Cell 1992;69:577–8.
Wattanagoon Y, Stepniewska K, Lindegardh N. Pharmacokinetics of high-dose oseltamivir in healthy volunteers. Antimicrob Agents Chemother 2009;53:945-52.
Dutkowski R, Smith JR, Davies BE. Safety and pharmacokinetics of oseltamivir at standard and high dosages. Int J Antimicrob Agents 2010;35:461-7.
Sharma PP, Roy RK, Anurag. Neuraminidase inhibitors: Oseltamivir, Peramivir, synthesis and profile. J Pharm Res 2010;3:1602-6.
He G, Massarella J, Ward P. Clinical pharmacokinetics of the prodrug oseltamivir and its active metabolite Ro 64-0802. Clin Pharmacokinet 1999;37:471-84.
Doucette KE, Aoki FY. Oseltamivir: a clinical and pharmacological perspective. Expert Opin Pharmacother 2001;2:1671-83.
Glaxo Smith Kline. Safety study to assess IV zanamivir for treatment of influenza infection in patients who are in hospital (NAI113678). Available from: http://clinicaltrials. gov/ct2/show/NCT01014988. [Last accessed on 11 Feb 2011]
Glaxo Smith Kline. A study of intravenous zanamivir versus oral oseltamivir in adults and adolescents hospitalized with influenza (ZORO). Available from: http://clinicaltrials.gov/ ct2/show/NCT01231620. [Last accessed on 11 Feb 2011]
Cass LM, Brown J, Pickford M. Pharmacoscintigraphic evaluation of lung deposition of inhaled zanamivir in healthy volunteers. Clin Pharmacokinet 1999;36(Suppl 1):21-31.
Bergstrom M, Cass LM, Valind S. Deposition and disposition of [11C] zanamivir following administration as an intranasal spray: evaluation with positron emission tomography. Clin Pharmacokinet 1999;36(Suppl 1):33-9.
Peng AW, Milleri S, Stein DS. Direct measurement of the antiinfluenza agent zanamivir in the respiratory tract following inhalation. Antimicrob Agents Chemother 2000;44:1974-6.
Calfee DP, Peng AW, Cass LM, Lobo M, Hayden FG. Safety and efficacy of intravenous zanamivir in preventing experimental human influenza a virus infection. Antimicrob Agents Chemother 1999;43:1616-20.
Bantia S, Parker CD, Ananth SL, et al. Comparison of the antiinfluenza virus activity of RWJ-270201 with those of oseltamivir and zanamivir. Antimicrob Agents Chemother 2001;45:1162-7.
Kohno S, Kida H, Mizuguchi M, Shimada J. Efficacy and safety of intravenous peramivir for treatment of seasonal influenza virus infection. Antimicrob Agents Chemother 2010;54:4568-74.
Itoh Y, Shinya K, Kiso M. In vitro and in vivo characterization of new swine-origin H1N1 influenza viruses. Nature 2009;460:1021-5.
Yamashita M, Tomozawa T, Kakuta M, Tokumitsu A, Nasu H, Kubo S. CS-8958, a prodrug of the new neuraminidase inhibitor R-125489, shows long-acting anti-influenza virus activity. Antimicrob Agents Chemother 2009;53:186-92.
Yamashita M. Laninamivir and its prodrug, CS-8958:long-acting neuraminidase inhibitors for the treatment of influenza. Antivir Chem Chemother 2010;21:71-84.
Koyama K, Ogura Y, Nakai D, Watanabe M, Munemasa T, Oofune Y, et al. Identification of bioactivating enzymes involved in the hydrolysis of laninamivir octanoate, a long-acting neuraminidase inhibitor, in human pulmonary tissue. Drug Metab Dispos 2014;42:1031–8.
B1eidner WE, Harmon JB, Hewes WE, Lynes TE, Hermann EC. Absorption, distribution and excretion of amantadine hydrochloride. J Pharmacol Exp Ther 1965;150:484-90.
Montanari C, Ferrari P, Bavazzano A. Urinary excretion of amantadine by the elderly. Eur J Clin Pharm 1975;8:349-51.
Koppel C, Tenczer J. A revision of the metabolic disposition of Amantadine. Biomed Mass Spectro 1985;12:499–501.
Hayden FG, Minocha A, Spyker DA, Hoffman HE. Comparative single dose pharmacokinetics of amantadine hydrochloride and rimantadine hydrochloride in young and elderly adults. Antimicrob Agents Chemother 1985;28:216-21.
Wills RJ. The clinical pharmacokinetics of rimantadine. J Respir Dis 1987;8(Suppl 11A):S39-44.
Capparelli EV, Stevens RC, Chow MS, Izard M, Wills RJ. Rimantadine pharmacokinetics in healthy subjects and patients with end-stage renal failure. Clin Pharmacol Ther 1988;43:536-41.
Rubio FR, Fukuda EK, Garland WA. Urinary metabolites of rimantadine in humans. Drug Metab Dispos BioI Fate Chern 1988;16:773-7.
Wills RJ, Belshe R, Tomlinsin D, De Grazia F, Lin A, Wells S. Pharmacokinetics of rimantadine hydrochloride in patients with chronic liver disease. Clin Pharmacol Ther 1987;42:449-54.
Rubio FR, Fukuda EK, Garland WA. Urinary metabolites of rimantadine in humans. Drug Metab Dispos 1988;16:773-7.
Wills RJ. Update on rimantadine's clinical pharmacokinetics. J Respir Dis 1989;10(Suppl):S20-5.
Rubio FA, Choma N, Fukuda EK. Determination of rimantadine and its hydroxylated metabolites in human plasma and urine. J Chromatogr 1989;497:147–57.
Brown SY, Garland WA, Fukuda EK. Isolation and characterization of an unusual glucuronide conjugate of rimantadine. Drug Metab Dispos BioI Fate Chern 1990;18:546-7.
Youssef RM, El-Yazbi EA, Khamis EF, Younis SE. Validated spectrophotometric methods for the evaluation of oseltamivir counterfeit pharmaceutical capsules; Bull Facul Pharm Cairo Uni 2014;52:63–9.
Bano T, Yadav G, Dudhe R. Development and validation of oseltamivir phosphate API by UV-spectrophotometer. Global J Pharm 2013;7:294-7.
Raut CS, Gharge DS, Dhabale PN, Gonjari ID, Hosmani AH, Hosmani AH. Development and validation of oseltamivir phosphate in fluvir® by UV-spectrophotometer. Int J PharmTech Res 2010;2:363-6.
Kumar JVS, Prasanthi S, Guravaiah M, Sekaran CB. Application of potassium permanganate to the spectrophotometric determination of oseltamivir phosphate in bulk and capsules. Asian J Pharm Clin Res 2012;5:18–22.
Nebsen M, Fattah SAA, Hassan DW, Youssef NF. Spectrophotometric and spectrofluorimetric determination of oseltamivir phosphate using 4-chloro-7-nitrobenzo-2-oxa 1, 3-diazole. Anal Chem Indian J 2011;10:336-41.
Reddy CMB, GV Reddy GVS. UV visible spectrophotometric estimation of Zanamvir. J Chem Pharm Res 2017;9:189-92.
Reddy CMB, Reddy GVS. A validated UV spectrophotometric determination of an antiviral drug zanamvir from tablet formulations. J Chem Pharm Res 2012;4:3624–7.
Omara HA, Amin AS. Extractive-spectrophotometric methods for determination of anti-parkinsonian drug in pharmaceutical formulations and in biological samples using sulphonphthalein acid dyes. J Saudi Chem Soc 2012;16:75-81.
Mahmoud AM, Khalil NY, Darwish IA, Aboul-Fadl T. Selective spectrophotometric and spectrofluorimetric methods for the determination of amantadine hydrochloride in capsules and plasma via derivatization with 1, 2-naphthoquinone-4-sulphonate. Int J Anal Chem 2009;810104:8. Doi:10.1155/ 2009/810104.
Gursoy A, Ozkirimli S, Ersoy O. Spectrophotometric determination of amantadine hydrochloride in capsules. J Fac Pharm Istanbul 1998;32:63–8.
Choi K, Choi JK, Yoo GS. Spectrophotometric determination of amantadine sulfate after ion-pairing with methyl orange. Arch Pharm Res 1991;14:285-9.
Muszalska I, Sobczak A, Kiaszewicz I, Rabiega K, Lesniewska MA, Jelińska A. 1, 2-Naphthoquinone-4-sulfonic acid sodium salt as a reagent for spectrophotometric determination of rimantadine and memantine. J Anal Chem 2015;70:320–7.
Bano T, Dudhe R, Kumar N. Development and validation of rp-hplc method for the determination of oseltamivir phosphate API. J Progr Res Chem 2015;2:69–73.
Kumar NM, Abbulu K, Narayana BV. Development and validation of stability indicating rp-hplc method for the determination of oseltamivir phosphate in oseltamivir phosphate capsules. Int J Res Chem Environ 2015;5:44–53.
Junaidy MAQ, Haque MA, Bakshi V. Rp-hplc method development and validation for the estimation of oseltamivir phosphate in bulk form and pharmaceutical formulations. Int J Innov Pharma Sci Res 2014;2:2786–91.
Ameti A, Slavkovska J, Starkoska K, Sarafinovska ZA. A simple isocratic rp-hplc method for quality control of oseltamivir capsules. Maced J Chem Eng 2012;31:205–15.
Sharma YK, Agarwal DD, Bhure S, Rathore SS, Rawat C, Mukharjee R. Synthesis, isolation and characterization of process–related impurities in oseltamivir phosphate. E-J Chem 2012;9:113–20.
Malipatil SM, Jahan K, Patil SK. Development and validation of rp-hplc method for the determination of oseltamivir phosphate in bulk drug and in dosage. Indo-Global J Pharma Sci 2011;1:57–62.
Sharma MC, Sharma S. Dissolution assessment and hplc method development and validation of oseltamivir phosphate in pharmaceutical formulation. Afr J Basic Appl Sci 2011;3:323–8.
Zeynep A, Sena C, Sıdıka T. Rp-hplc method for determination of oseltamivir phosphate in capsules and spiked plasma. Anal Lett 2010;43:2200–9.
Nagarajan JSK, Muralidharan S. A validated RP-HPLC method for estimation of Oseltamivir in pharmaceutical formulation. Der Pharm Lett 2009;1:162–8.
Green MD, Nettey H, Wirtz RA. Determination of oseltamivir quality by colorimetric and liquid chromatographic methods. Emer Infect Dis 2008;14;552–6.
Narasimhan B, Abida K, Srinivas K. Stability indicating RP-HPLC method development and validation for oseltamivir API. Chem Pharm Bull 2008;56:413–7.
Raghuram P, Raju IVS, Reddy R, Sriramulu J. A stability indicating LC method for oseltamivir phosphate. Anal Chem Indian J 2008;7:617–24.
Bahrami G, Mohammadi B, Kiani A. Determination of oseltamivir carboxylic acid in human serum by solid phase extraction and high performance liquid chromatography with UV detection. J Chromatogr B 2008;864:38–42.
Charles JJ, Geneste C, Kummer EL, Gheyouche R, Boudis H, Dubost JP. Development and validation of a rapid HPLC method for the determination of oseltamivir phosphate in Tamiflu and generic versions. J Pharma Biomed Anal 2007;44:1008–13.
Rajendran R, Devika S, Sura RS, Sunil V, Kumar MB, Gopinath P, et al. RP-HPLC pda method for estimation of zanamivir in api and pharmaceutical formulation. Indo Am J Pharm Sci 2018;5:2110–6.
Bhirud CH, Nandal DH. Stability indicating RP-HPLC and HPTLC methods for the determination of zanamivir in bulk and dosage form. Int J Pharm Sci 2016;8:249–56.
Reddy YR, Harika KSL, Sowjanya KS, Swathi E, Soujanya B, Reddy SS. Estimation of zanamivir drug present in tablets using RP-HPLC method. Int J PharmTech Res 2011;3:180–6.
Boonyapiwat B, Sarisuta N, Ma Y, Steventon GB. A validated HPLC method for zanamivir and its application to in vitro permeability study in caco-2 culture model. Indian J Pharm Sci 2011;73:564–8.
Erk N. A validated HPLC method for the determination of the neuraminidase inhibitor, zanamivir (gg167), in spiked human plasma and in pharmaceutical formulations. J Liq Chromatogr Related Tech 2004;27:1541–52.
Wang F, Zhang S, Sheng C, Zhao X, You J. Sensitive determination of amantadine in microdialysis samples from rat plasma by HPLC with fluorescence detection. J Liq Chromatogr Relat Technol 2015;38:1622–8.
Yanamadala G, Lavanya N, Srikumar PP. A pre-column derivatization technique for the development and validation of a HPLC-UV method for the determination of amantadine hydrochloride in bulk and formulations by using (2-napthoxy) acetyl chloride. Acta Chim Pharm Indica 2014;4:170–9.
Vemuri SK, Krishna NR, Mohammad MJ, Nalluri BN. Analysis of amantadine hydrochloride-phenyl isothiocyanate complex in bulk and pharmaceutical dosage forms by RP HPLC-PDA method. Br J Pharma Res 2014;4:278–88.
Darwish IA, Aboul FT, Khalil NY, Mahmoud AM, Al-Obaid AM. New sensitive hplc method for evaluation of the pharmacokinetics of new amantadine prodrugs as hepatic delivery systems to enhance its activity against HCV. Int J Res Pharm Sci 2010;1:151–7.
Yihua Z, Jianguo J, Xuejing H, Shiliang Z. Simultaneous determination of three components in pediatric paracetamol and amantadine hydrochloride granules using high performance liquid chromatography with gradient elution and dual wavelength detection. Chin J Chromatogr 2010;28:1005–8.
Shuangjin C, Fang F, Han L, Ming M. New method for high-performance liquid chromatographic determination of amantadine and its analogues in rat plasma. J Pharma Biomed Anal 2007;44:1100–5.
Higashi Y, Uemori I, Fujii Y. Simultaneous determination of amantadine and rimantadine by hplc in rat plasma with pre-column derivatization and fluorescence detection for pharmacokinetic studies. Biomed Chromatogr 2005;19:655–62.
Mamatha J, Devanna N. Development and validation of a rp–hplc method for the analysis of rimantadine hydrochloride in medicinal form. Rasayan J Chem 2018;11:300–6.
Zacharis CK, Tzanavaras PD, Vlessidis AG. Determination of rimantadine in human urine by hplc using a monolithic stationary phase and on-line post-column derivatization. J Sep Sci 2013;00:1–6.
Bhirud CH, Nandal DH. Development and validation of stability indicating hptlc method for the determination of oseltamivir phosphate in bulk and dosage form. Int J Pharm Pharma Res 2017;9:299–311.
Al Bratty M, Saleh SF, Alhazmi HA, Javed SA, Ahmed AM, Ahsan W. A validated hptlc densitometric method for quantitative determination of zanamivir in bulk and pharmaceutical formulation. Eur J Chem 2018;9:115–20.
Kummer EL, Gaudin K, Charles JJ, Gheyouche R, Boudis H, Dubost JP. Development and validation of a rapid capillary electrophoresis method for the determination of oseltamivir phosphate in Tamiflu and generic versions. J Pharma Biomed Anal 2009;50:544–6.
Pazourek J, Revilla AL, Gajdosova D, Havel J. Validation of a capillary zone electrophoresis method for determination of rimantadine hydrochloride in rimantadine 100 tablets and the method application to dissolution test monitoring. Drug Dev Ind Pharm 2004;30:125–34.
Revilla AL, Hamacek J, Lubal P, Havel J. Determination of rimantadine in pharmaceutical preparations by capillary zone electrophoresis with indirect detection or after derivatization. Chromatogr 1998;47:433-9.
Rashed NS, Abdallah OM, Said NS. Validated stability–indicating methods for determination of oseltamivir phosphate. Br J Pharma Res 2017;16:1-9.
Mehta SD, Paliwal S. Phytochemical analysis, liquid chromatography, and mass spectroscopy and in vitro anticancer activity of annona squamosa seeds linn. Asian J Pharm Clin Res 2018;11:101–3.
Nagappan K, Yamjala K, Sathyaseelan M, Byran G. Stability evaluation of tartrazine by liquid chromatography-diode array detector and high-resolution electron spray ionization quadrupole time-of-flight mass spectrometry/mass spectrometry analysis. Asian J Pharm Clin Res 2017;10:295–9.
Virani P, Sojitra R, Raj H, Jain V. Chromatographic method for irbesartan and its combination with other drug. J Crit Rev 2015;2:7-11.
Pradeep PS, Shrungesh KTO, Prashantha N, Mahadevan KM. Synthesis, in vitro antibacterial, toxicity and molecular docking anticancer activity of novel n-[(2-chloroquinolin-3-yl) methylidene]-2-aniline Schiff bases. Int J Curr Pharm Res 2015;7:37-46.
Yahdiana H, Norma A, Harmita. Method development and validation of lercanidipine in human plasma by liquid chromatography tandem-mass spectrometry. Int J Appl Pharm 2018;10:87-91.
Bhadoriya A, Rathnam S, Dasandi B, Parmar D, Sanyal M, Shrivastav PS. Sensitive and rapid determination of amantadine without derivatization in human plasma by LC–MS/MS for a bioequivalence study. J Pharma Anal 2018;8:202–7.
Wang K, Chen M, Weng H, Gao Y, Zhao H, Lin Z. Validation of a robust and high-throughput HPLC-MS/MS method to determine Amantadine levels in human plasma. J Appl Bioanal 2018;4:51-61.
Tsuruoka Y, Nakajima T, Kanda M, Hayashi H, Matsushima Y, Yoshikawa S, et al. Simultaneous determination of amantadine, rimantadine, and memantine in processed products, chicken tissues, and eggs by liquid chromatography with tandem mass spectrometry. J Chromatogr B 2017;1044–1045:142–8.
Turnipseed SB, Storey JM, Andersen WC, Filigenzi MS, Heise AS, Lohne JJ, et al. Determination and confirmation of the antiviral drug amantadine and its analogues in chicken jerky pet treats. J Agric Food Chem 2015;63:6968−78.
Lindberg RH, Fedorova G, Blum KM, Pulit-Prociak J, Gillman A, Jarhult J, et al. Online solid phase extraction liquid chromatography using bonded zwitterionic stationary phases and tandem mass spectrometry for rapid environmental trace analysis of highly polar hydrophilic compounds–application for the antiviral drug Zanamivir. Talanta 2015;141:164–9.
Janiwarad S, Haq KU, Choudhary D. A selective and sensitive liquid chromatographic/tandem mass spectrometric method for simultaneous estimation of oseltamivir and its metabolite oseltamivir carboxylic acid in human plasma for bioavailability or bioequivalence studies. World J Pharma Res 2014;3:4598-614.
Zhao S, Li D, Qiu J, Wang M, Yang S, Chen D. Simultaneous determination of amantadine, rimantadine and chlorpheniramine in animal derived food by liquid chromatography-tandem mass spectrometry after fast sample preparation. Anal Methods 2014;6:7062–7.
Hu ZY, Laizure SC, Meibohm B, Herring VL, Parker RB. Simple and sensitive assay for quantification of oseltamivir and its active metabolite oseltamivir carboxylate in human plasma using high-performance liquid chromatography coupled with electrospray ionization tandem mass spectrometry: improved applicability to pharmacokinetic study. J Pharma Biomed Anal 2013;72:245–50.
Gupta A, Guttikar S, Shrivastav PS, Sanyal M. Simultaneous quantification of prodrug oseltamivir and its metabolite oseltamivir carboxylate in human plasma by LC–MS/MS to support a bioequivalence study. J Pharma Anal 2013;3:149–60.
Lin CC, Yen JC, Wu YT, Lin LC, Tsai TH. Chemical analysis and transplacental transfer of oseltamivir and oseltamivir carboxylic acid in pregnant rats. PLoS One 2012;7:e46062.
Berendsen BJA, Wegh RS, Essers ML, Stolker AAM, Weigel S. Quantitative trace analysis of a broad range of antiviral drugs in poultry muscle using column-switch liquid chromatography coupled to tandem mass spectrometry. Anal Bioanal Chem 2012;402:1611–23.
Kromdijk W, Rosing H, Van den Broek MPH, Beijnen JH, Huitema ADR. Quantitative determination of oseltamivir and oseltamivir carboxylate in human fluoride EDTA plasma including the ex vivo stability using high-performance liquid chromatography coupled with electrospray ionization tandem mass spectrometry. J Chromatogr B 2012;891–892:57–63.
Lindegardh N, Hanpithakpong W, Kamanikom B, Farrar J, Hien TT, Singhasivanon P, et al. Quantification of the anti-influenza drug zanamivir in plasma using high-throughput HILIC–MS/MS. Bioanal 2011;3:157–65.
Kanneti R, Bhavesh D, Paramar D, Shivaprakash R, Bhatt PA. Development and validation of a high-throughput and robust LC–MS/MS with electrospray ionization method for simultaneous quantitation of oseltamivir phosphate and its oseltamivir carboxylate metabolite in human plasma for pharmacokinetic studies. Biomed Chromatogr 2011;25:727–33.
Baughman TM, Wright WL, Hutton KA. Determination of zanamivir in rat and monkey plasma by positive ion hydrophilic interaction chromatography (HILIC)/tandem mass spectrometry. J Chromatogr B 2007;852:505–11.
Arndt T, Guessregen B, Hohl A, Reis J. Determination of serum amantadine by liquid chromatography-tandem mass spectrometry. Clin Chim Acta 2005;359:125–31.
Jia Q, Li D, Wang X, Yang S, Qian Y, Qiu J. Simultaneous determination of amantadine and rimantadine in feed by liquid chromatography-Qtrap mass spectrometry with information-dependent acquisition. Anal Bioanal Chem 2018;410:5555–65.
Mu P, Xu N, Chai T, Jia Q, Yin Z, Yang S, et al. Simultaneous determination of 14 antiviral drugs and relevant metabolites in chicken muscle by UPLC–MS/MS after QuEChERS preparation. J Chromatogr B 2016;1023–1024:17–23.
Azuma T, Ishiuchi H, Inoyama T, Teranishi Y, Yamaoka M, Sato T, et al. Detection of peramivir and laninamivir, new anti-influenza drugs, in sewage effluent and river waters in japan. PloS One 2015;10:e0131412.
Takanami R, Ozaki H, Giri RR, Taniguchi S, Hayashi S. Antiviral drugs zanamivir and oseltamivir found in wastewater and surface water in Osaka, Japan. J Water Environ Tech 2012;10:57–68.
Takanami R, Ozaki H, Giri RR, Taniguchi S, Hayashi S. Detection of antiviral drugs oseltamivir phosphate and oseltamivir carboxylate in neya river, Osaka, Japan. J Water Environ Tech 2010;8:363–72.
Yan H, Liu X, Cui F, Yun H, Li J, Ding S, et al. Determination of amantadine and rimantadine in chicken muscle by QuEChERS pretreatment method and UHPLC coupled with LTQ Orbit rap mass spectrometry. J Chromatogr B 2013;938:8–13.
Wu YL, Chen RX, Xue Y, Yang T, Zhao J, Zhu Y. Simultaneous determination of amantadine, rimantadine and memantine in chicken muscle using multi-walled carbon nanotubes as a reversed-dispersive solid phase extraction sorbent. J Chromatogr B 2014;965:197–205.
Hooff GP, Meesters RJW, Van Kampen JJA, Van Huizen NA, Koch B, Al Hadithy AFY, et al. Dried blood spot UHPLC-MS/MS analysis of oseltamivir and oseltamivir carboxylate—a validated assay for the clinic. Anal Bioanal Chem 2011;400:3473–79.