Dr Philip W. Lee, School of Pharmacy, East China University of Science and Technology, Shanghai, Peoples' Republic of China.Dr. Philip W. Lee has more than 35 years of industrial experience in the field of agrochemical research and development. He is currently Professor at School of Pharmacy, East China University of Science and Technology. He has published more than 40 scientific articles in pesticides and drug metabolism and environmental chemistry.Dr. Lee is a contributing editor for the Volume 1 and 2 of the Metabolic Pathways of Agrochemicals, published by Royal Society of Chemistry (RSC) in 1998 and 1999, and is the Editor-in-Chief of a 2-volume Handbook of Residue Analytical Methods for Agrochemicals, published by Wiley in 2003. He is the editor of Pesticide Chemistry: Crop Protection, Public Health and Environmental Safety, conference proceeding book of the 2006 IUPAC International Pesticide Congress, Kobe, Japan, published by Wiley-VCH, 2007.Hiroyasu Aizawa, Hiro Research Consultancy Inc. (HRCI), Toyko, Japan.Lawrence L. Gan, Biogen Idec, Inc., Cambridge, MA, USA.Chandra C. Prakash, Biogen Idec, Inc., Cambridge, MA, USA.Dafang D. Zhong, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, Peoples' Republic of China.Dr. Hiro Aizawa has been active for more than 20 years in the study of animal drug metabolism. Dr Lawrence Gan and Dr. Chandrah Prakash are active with a long experience in the development of human drugs and the study of human drug metabolism.

• Volume 1About the Editors xxxiiiPreface xxxviiList of Contributors of Volumes 1 and 2 xxxixAbbreviations and Acronyms xliA personal and historical perspective on drug metabolism 1Gerald T. Miwa and Arthur K. ChoFundamentals of organic chemistry as applicable to the biotransformation of foreign compounds 27Antonia F. Stepan and Amit S. KalgutkarFunctional group biotransformations 61R. Scott ObachDrugs as victims and perpetrators and the pharmacokinetic concept of maximum exposure 103Brian W. Ogilvie and Andrew ParkinsonDrug-metabolizing enzymes: a group of promiscuous catalysts 125Qiang Ma and Anthony Y.H. LuUnusual metabolic reactions and pathways 147F. Peter Guengerich and Emre M. IsinRole of biotransformation in drug discovery 199Ronald E. WhiteRole of metabolism in drug development 215Role of biotransformation in pesticide discovery and development 233Michael E. Krolski and Stephen C. DacusRole of cytochrome P450 enzymes in biotransformation 249Paul R. Ortiz de MontellanoMajor human conjugative drug-metabolizing enzymes 267Daniel R. Albaugh and Michael B. FisherMetabolic activation and associated drug toxicity 303Thomas A. BaillieIn vitro experimental models for studying drug biotransformation 321Tonika Bohnert and Lawrence L. GanIn vivo experimental models for studying drug biotransformation 383W. Griffith HumphreysVolume 2About the Editors xxxiiiPreface xxxviiList of Contributors of Volumes 1 and 2 xxxixAbbreviations and Acronyms xliTheory and instrumentation of mass spectrometry and its application to drug metabolism 393Stacy L. Gelhaus and Ian A. BlairMass spectral interpretation 419Li-Kang Zhang and Birendra N. PramanikComputational approaches in drug biotransformation studies: metabolite prediction 457Nigel J. Waters and Michelle K. DennehyHigh-throughput metabolite detection and quantitative–qualitative bioanalysis 481Donghui Cui and Sean YuMetabolic stability screen in drug discovery 499Chuang LuApplication of triple-quadrupole and its hybrid mass spectrometers for the identification of drug metabolites 523Zhi-Yi Zhang, Chandra Prakash, and Lin XuRole of ion trap LC-MS techniques for the identification of drug metabolites 553Robert D. Pelletier and W. George LaiDrug metabolite identification with high-resolution mass spectrometry 567Haiying Zhang and Mingshe ZhuStrategies for the identification of unusual and novel metabolites using derivatization, hydrogen–deuterium exchange (HDX), and liquid chromatography-nuclear magnetic resonance (LC-NMR) spectroscopy techniques 591Amin Kamel, Shawn Harriman, and Chandra PrakashThe use of nanoelectrospray mass spectrometry for the quantitation of metabolites in the absence of synthetic standards 619Jing-Tao WuQuantitation of drug metabolites by radioactivity detection including accelerator mass spectrometry (AMS) 633Angus N.R. Nedderman and Mark E. SavageApplication of quantitative NMR in drug metabolism studies 661Abdul E. MutlibEarly assessment of exposure of drug metabolites in humans using mass spectrometry 693Natalia A. Penner, Joanna Zgoda-Pols, and Chandra PrakashProfiling and characterization of bioactive substances of herbal medicine and their metabolites using mass spectrometry 723Xiaoyan ChenApplication of in silico metabolism and environmental degradation data to support chemical PBT assessment 787Sabcho Dimitrov, Gilman Veith, and Ovanes MekenyanVolume 3About the Editors xxxiiiPreface xxxviiList of Data Compilers of Volumes 3–5 xxxixAbbreviations and Acronyms xliAbacavir 809Acebutolol 813Acequinocyl 815Acetaminophen 821Acibenzolar-S -methyl 825Acyclovir 829Adapalene 832Adonifoline 834Albuterol 837Alendronate 840Alfentanil 842Aliskiren 847Alloxan 849Almotriptan 851Alprazolam 856Amantadine 859Ambroxol 861Amiodarone 864Amisulbrom 867Amitriptyline 875Amlodipine 878Amoxicillin 884Amphetamine 887Anastrozole 889trans-Anethole 892Aniracetam 895Antipyrine 898Apixaban 902Apremilast 905Aprepitant 909Aranidipine 913Arbidol 915Aripiprazole 918Asenapine 921Aspirin 924Atazanavir 927Atenolol 931Atomoxetine 933Atorvastatin 937Azelastine 942Barnidipine 945Benazepril 949Bendamustine 952Benfuresate 956Benidipine 959Benthiavalicarb isopropyl 964Benzophenone 969Benzoyl peroxide 972Berberine 974Betaxolol 979Bexarotene 981Bicalutamide 986Bicifadine 990Bimatoprost 994Bisoprolol 996BMS-214778 999Boceprevir 1002Bortezomib 1006Bosentan 1009Brimonidine 1012Brivaracetam 1015Bromhexine 1018Brompheniramine 1024Budesonide 1027Buprenorphine 1030Bupropion 1033Buspirone 1036Butalbital 10413-n-Butylphthalide 1043Caffeine 1047Calcipotriene 1051Candesartan 1054Capecitabine 1057Capravirine 1061Captopril 1067Carazolol 1070Carfilzomib 1072Carvedilol 1076Casopitant 1081Cefdinir 1085Cefepime 1088Celecoxib 1090Cetirizine 1094Chlorpheniramine 1098Chlorpromazine 1102Cholecalciferol 1106Cibenzoline 1110Ciclesonide 1113Cidofovir 1118Cinacalcet 1121Ciprofloxacin 1125Cisapride 1128Cladribine 1136Clebopride 1139Clenbuterol 1142Clindamycin 1145Clobazam 1147Clofarabine 1151Clofibrate 1154Clopidogrel 1156Coumarin 1159Cyclamate 1163Cyclobenzaprine 1165Dabigatran 1170Darifenacin 1174Darunavir 1177Dauricine 1181Degarelix 1186Desloratadine 1190Dexamethasone 1193Dexfenfluramine 1196Dexmethylphenidate 1198Dextroamphetamine 1201Diazepam 1204Diazoxide 1208Dichlobenil 1210Dichlorprop 1212Diclofenac 1214Diclosulam 1218Difloxacin 1220Digoxin 1223Diltiazem 1227Diniconazole-M 1230Dinotefuran 1232Diphenhydramine 1237Dipyridamole 1241Divalproex 1244Domperidone 1249Donepezil 1253Dopamine 1257Doripenem 1260Dorzolamide 1263Doxazosin 1266Doxorubicin 1269Dronabinol 1274Drospirenone 1278Duloxetine 1281Dutasteride 1283Edoxaban 1286Efavirenz 1291Eletriptan 1297Eltrombopag 1299Elzasonan 1302Emtricitabine 1305Enalapril 1308Enfuvirtide 1311Enoxaparin 1315Eplerenone 1318Erdosteine 1322Erlotinib 1324Ertugliflozin 1327Escitalopram 1331Esomeprazole 1335Estazolam 1338Estrogens 1341Ethinylestradiol 1347Ethionamide 1350Ethiprole 1354Ethoxysulfuron 1360Etonogestrel 1362Etoricoxib 1365Etridiazole 1368Exemestane 1370Ezetimibe 1373Ezlopitant 1377Chemical Name Index ICAS Number Index IXVolume 4About the Editors xxxiiiPreface xxxviiList of Data Compilers of Volumes 3–5 xxxixAbbreviations and Acronyms xliFamciclovir 1381Famitinib 1385Famotidine 1391FDDNP 1393Febuxostat 1395Felodipine 1399Fenazaquin 1404Fenofibrate 1406Fenpropimorph 1411Fenproporex 1416Fenpyroximate 1419Fentanyl 1422Fexofenadine 1425Finasteride 1427Fingolimod 1431Flonicamid 1435Fluazinam 1439Fluconazole 1444Flumioxazin 1446Flunarizine 1450Flunitrazepam 1455Fluopicolide 1458Fluoxastrobin 1462Flupyrsulfuron methyl 1467Fluroxypyr 1469Flutamide 1471Fluticasone furoate 1475Fluticasone propionate 1478Fluvastatin 1480Fluvoxamine 1483Forchlorfenuron 1487Fosinopril 1489Furametpyr 1492Gabapentin 1495Galantamine 1497Gambogic acid 1502Ganoderic acid D 1506Garenoxacin 1509Gefitinib 1511Gemfibrozil 1516Gemopatrilat 1522Genipin 1525Glafenine 1527Glatiramer acetate 1531Gliclazide 1533Glipizide 1536Granisetron 1538Harmaline 1541Hexaconazole 1543Hydrochlorothiazide 1546Hydrocodone (oxycodone) 1548Hydroxychavicol 1551Ibandronate 1553Ibuprofen 1555Ilaprazole 1559Iloperidone 1562Imatinib 1567Imazamethabenz-methyl 1571Imazamox 1573Imazosulfuron 1577Imidafenacin 1579Imiprothrin 1582Imiquimod 1584Imrecoxib 1587Indacaterol 1590Indapamide 1593Indinavir 1597Ipconazole 1601Ipratropium 1603Irbesartan 1606Irinotecan 1609Irofulven 1614Isoeugenol 1617Isoxaflutole 1619Isoxicam 1621Ivermectin 1624Ixabepilone 1628Lamivudine 1632Lamotrigine 1634Lansoprazole 1638Lapatinib 1640Laropiprant 1643Lasofoxifene 1647Latanoprost 1651Lefucoxib 1655Lersivirine 1657Letosteine 1660Letrozole 1662Levalbuterol 1665Levocetirizine 1668Levofloxacin 1671Levonorgestrel 1673Levothyroxine 1677Lidocaine 1679Linagliptin 1682Lindane 1685Linezolid 1687Lithocholic acid 1690Lithospermic acid 1693Lopinavir 1696Loratadine 1701Lorazepam 1706Losartan 1710Lovastatin 1715Lufenuron 1719Lumiracoxib 1723Lurasidone 1726Mandipropamid 1732Mebeverine 1738Medroxyprogesterone acetate 1741Meisoindigo 1745Meloxicam 1747Memantine 1752Menadione 1754Mesalamine 1758Mesosulfuron-methyl 1761Mesotrione 1764Metaxalone 1767Metformin 1769Methadone 1771Methoxyfenozide 1775Methyldopa 1780Methylphenidate 1783Metoclopramide 1786Metofluthrin 1790Metoprolol 1792Metoxuron 1795Metronidazole 1797Mexiletine 1800Mianserin 1803Mifepristone 1808Milnacipran 1812Minocycline 1814Mirabegron 1816Misoprostol 1819Modafinil 1821Mometasone furoate 1824Montelukast 1827Moricizine 1830Morinidazole 1833Moxifloxacin 1836Moxonidine 1838Mycophenolate mofetil 1841Nabumetone 1845Naloxone 1847Nateglinide 1850Nevirapine 1853Niacin 1858Nicardipine 1861Nicotine 1865Nifedipine 1870Nilotinib 1874Nilutamide 1878Nimodipine 1881Nizatidine 1885Norelgestromin 1888Norfloxacin 1891Norgestimate 1893Nortriptyline 1897Novaluron 1900Chemical Name Index ICAS Number Index IXVolume 5About the Editors xxxiiiPreface xxxviiList of Data Compilers of Volumes 3–5 xxxixAbbreviations and Acronyms xliOlanzapine 1905Olmesartan medoxomil 1909Olopatadine 1912Omeprazole 1915Ondansetron 1918Ornidazole 1921Orphenadrine 1923Oxadiargyl 1925Oxcarbazepine 1930Oxybenzone 1933Oxycodone 1936Paclitaxel 1940Paclobutrazol 1945Paeonol 1949Paliperidone 1951Pantoprazole 1953Paroxetine 1957Pefloxacin 1960Peliglitazar 1962Penthiopyrad 1965Pentoxazone 1970Perphenazine 1972Phenolphthalein 1976Picolinafen 1978Pindolol 1981Pioglitazone 1984Piperacillin 1988Piroxicam 1991Pirprofen 1993Pitavastatin 1998Pramipexole 2004Pravastatin 2006Prazosin 2012Pregabalin 2016Prochloraz 2018Propafenone 2020Prosulfuron 2024Prothioconazole 202720(S )-Protopanaxadiol 2030Proxyphylline 2033Pseudoephedrine 2035(2S )-Pterosin A 2037Pyraflufen-ethyl 2039Pyrasulfotole 2042Pyrazosulfuron methyl 2045Pyribenzoxim 2047Pyridalyl 2050Pyrimethanil 2055Quetiapine 2058Rabeprazole 2061Raloxifene 2065Ramelteon 2069Ranitidine 2072Repaglinide 2075Rifapentine 2079Risedronate 2082Risperidone 2084Ritonavir 2087Rivaroxaban 2092Rizatriptan 2096Rofecoxib 2100Roflumilast 2105Ropinirole 2107Rosiglitazone 2110Rosuvastatin 2115Rotigotine 2119Ruboxistaurin 2122Rufinamide 2125Ruxolitinib 2127Salmeterol 2130Sameridine 2133Saxagliptin 2136Selegiline 2139Seliciclib 2142Sertraline 2145Silafluofen 2149Sildenafil 2151Simvastatin 2155Sitagliptin 2160Sorafenib 2164Sudoxicam 2166Sulcotrione 2169Sulindac 2172Sumatriptan 2175Sunepitron 2178Tacrolimus 2183Tadalafil 2187Tafluprost 2190Tamoxifen 2193Tamsulosin 2197Telmisartan 2200Temozolomide 2202Tenofovir 2205Tepraloxydim 2208Terazosin 2212Terbinafine 2215Tetraconazole 2219Thalidomide 2222Theophylline 2226Thiamethoxam 2231Ticagrelor 2236Ticlopidine 2239Timolol 2242Tinidazole 2245Tiotropium 2247Tipranavir 2250Tirapazamine 2253Tobramycin 2255Tolbutamide 2257Tolcapone 2261Tolfenpyrad 2265Tolterodine 2267Tolvaptan 2270Topiramate 2274Torcetrapib 2277Tramadol 2281Trandolapril 2284Traxoprodil 2286Triamcinolone 2289Triamcinolone acetonide 2291Triasulfuron 2294Triclosan 2296Trimebutine 2298Tropisetron 2302Vabicaserin 2305Valacyclovir 2310Valdecoxib 2313Valsartan 2317Vardenafil 2319Varenicline 2322Vemurafenib 2325Venlafaxine 2328Verapamil 2332Veratridine 2336Vilanterol 2339Vildagliptin 2343Vinorelbine 2348Vismodegib 2353Warfarin 2357Ximelagatran 2361Zafirlukast 2363Zearalenone 2366Zibotentan 2369Zidovudine 2372Ziprasidone 2375Zofenopril 2382Zolmitriptan 2385Zolpidem 2387Chemical Name Index ICAS Number Index IX

Dr Philip W. Lee, School of Pharmacy, East China University of Science and Technology, Shanghai, Peoples' Republic of China.Dr. Philip W. Lee has more than 35 years of industrial experience in the field of agrochemical research and development. He is currently Professor at School of Pharmacy, East China University of Science and Technology. He has published more than 40 scientific articles in pesticides and drug metabolism and environmental chemistry.Dr. Lee is a contributing editor for the Volume 1 and 2 of the Metabolic Pathways of Agrochemicals, published by Royal Society of Chemistry (RSC) in 1998 and 1999, and is the Editor-in-Chief of a 2-volume Handbook of Residue Analytical Methods for Agrochemicals, published by Wiley in 2003. He is the editor of Pesticide Chemistry: Crop Protection, Public Health and Environmental Safety, conference proceeding book of the 2006 IUPAC International Pesticide Congress, Kobe, Japan, published by Wiley-VCH, 2007.Hiroyasu Aizawa, Hiro Research Consultancy Inc. (HRCI), Toyko, Japan.Lawrence L. Gan, Biogen Idec, Inc., Cambridge, MA, USA.Chandra C. Prakash, Biogen Idec, Inc., Cambridge, MA, USA.Dafang D. Zhong, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, Peoples' Republic of China.Dr. Hiro Aizawa has been active for more than 20 years in the study of animal drug metabolism. Dr Lawrence Gan and Dr. Chandrah Prakash are active with a long experience in the development of human drugs and the study of human drug metabolism.

• Volume 1About the Editors xxxiiiPreface xxxviiList of Contributors of Volumes 1 and 2 xxxixAbbreviations and Acronyms xliA personal and historical perspective on drug metabolism 1Gerald T. Miwa and Arthur K. ChoFundamentals of organic chemistry as applicable to the biotransformation of foreign compounds 27Antonia F. Stepan and Amit S. KalgutkarFunctional group biotransformations 61R. Scott ObachDrugs as victims and perpetrators and the pharmacokinetic concept of maximum exposure 103Brian W. Ogilvie and Andrew ParkinsonDrug-metabolizing enzymes: a group of promiscuous catalysts 125Qiang Ma and Anthony Y.H. LuUnusual metabolic reactions and pathways 147F. Peter Guengerich and Emre M. IsinRole of biotransformation in drug discovery 199Ronald E. WhiteRole of metabolism in drug development 215Role of biotransformation in pesticide discovery and development 233Michael E. Krolski and Stephen C. DacusRole of cytochrome P450 enzymes in biotransformation 249Paul R. Ortiz de MontellanoMajor human conjugative drug-metabolizing enzymes 267Daniel R. Albaugh and Michael B. FisherMetabolic activation and associated drug toxicity 303Thomas A. BaillieIn vitro experimental models for studying drug biotransformation 321Tonika Bohnert and Lawrence L. GanIn vivo experimental models for studying drug biotransformation 383W. Griffith HumphreysVolume 2About the Editors xxxiiiPreface xxxviiList of Contributors of Volumes 1 and 2 xxxixAbbreviations and Acronyms xliTheory and instrumentation of mass spectrometry and its application to drug metabolism 393Stacy L. Gelhaus and Ian A. BlairMass spectral interpretation 419Li-Kang Zhang and Birendra N. PramanikComputational approaches in drug biotransformation studies: metabolite prediction 457Nigel J. Waters and Michelle K. DennehyHigh-throughput metabolite detection and quantitative–qualitative bioanalysis 481Donghui Cui and Sean YuMetabolic stability screen in drug discovery 499Chuang LuApplication of triple-quadrupole and its hybrid mass spectrometers for the identification of drug metabolites 523Zhi-Yi Zhang, Chandra Prakash, and Lin XuRole of ion trap LC-MS techniques for the identification of drug metabolites 553Robert D. Pelletier and W. George LaiDrug metabolite identification with high-resolution mass spectrometry 567Haiying Zhang and Mingshe ZhuStrategies for the identification of unusual and novel metabolites using derivatization, hydrogen–deuterium exchange (HDX), and liquid chromatography-nuclear magnetic resonance (LC-NMR) spectroscopy techniques 591Amin Kamel, Shawn Harriman, and Chandra PrakashThe use of nanoelectrospray mass spectrometry for the quantitation of metabolites in the absence of synthetic standards 619Jing-Tao WuQuantitation of drug metabolites by radioactivity detection including accelerator mass spectrometry (AMS) 633Angus N.R. Nedderman and Mark E. SavageApplication of quantitative NMR in drug metabolism studies 661Abdul E. MutlibEarly assessment of exposure of drug metabolites in humans using mass spectrometry 693Natalia A. Penner, Joanna Zgoda-Pols, and Chandra PrakashProfiling and characterization of bioactive substances of herbal medicine and their metabolites using mass spectrometry 723Xiaoyan ChenApplication of in silico metabolism and environmental degradation data to support chemical PBT assessment 787Sabcho Dimitrov, Gilman Veith, and Ovanes MekenyanVolume 3About the Editors xxxiiiPreface xxxviiList of Data Compilers of Volumes 3–5 xxxixAbbreviations and Acronyms xliAbacavir 809Acebutolol 813Acequinocyl 815Acetaminophen 821Acibenzolar-S -methyl 825Acyclovir 829Adapalene 832Adonifoline 834Albuterol 837Alendronate 840Alfentanil 842Aliskiren 847Alloxan 849Almotriptan 851Alprazolam 856Amantadine 859Ambroxol 861Amiodarone 864Amisulbrom 867Amitriptyline 875Amlodipine 878Amoxicillin 884Amphetamine 887Anastrozole 889trans-Anethole 892Aniracetam 895Antipyrine 898Apixaban 902Apremilast 905Aprepitant 909Aranidipine 913Arbidol 915Aripiprazole 918Asenapine 921Aspirin 924Atazanavir 927Atenolol 931Atomoxetine 933Atorvastatin 937Azelastine 942Barnidipine 945Benazepril 949Bendamustine 952Benfuresate 956Benidipine 959Benthiavalicarb isopropyl 964Benzophenone 969Benzoyl peroxide 972Berberine 974Betaxolol 979Bexarotene 981Bicalutamide 986Bicifadine 990Bimatoprost 994Bisoprolol 996BMS-214778 999Boceprevir 1002Bortezomib 1006Bosentan 1009Brimonidine 1012Brivaracetam 1015Bromhexine 1018Brompheniramine 1024Budesonide 1027Buprenorphine 1030Bupropion 1033Buspirone 1036Butalbital 10413-n-Butylphthalide 1043Caffeine 1047Calcipotriene 1051Candesartan 1054Capecitabine 1057Capravirine 1061Captopril 1067Carazolol 1070Carfilzomib 1072Carvedilol 1076Casopitant 1081Cefdinir 1085Cefepime 1088Celecoxib 1090Cetirizine 1094Chlorpheniramine 1098Chlorpromazine 1102Cholecalciferol 1106Cibenzoline 1110Ciclesonide 1113Cidofovir 1118Cinacalcet 1121Ciprofloxacin 1125Cisapride 1128Cladribine 1136Clebopride 1139Clenbuterol 1142Clindamycin 1145Clobazam 1147Clofarabine 1151Clofibrate 1154Clopidogrel 1156Coumarin 1159Cyclamate 1163Cyclobenzaprine 1165Dabigatran 1170Darifenacin 1174Darunavir 1177Dauricine 1181Degarelix 1186Desloratadine 1190Dexamethasone 1193Dexfenfluramine 1196Dexmethylphenidate 1198Dextroamphetamine 1201Diazepam 1204Diazoxide 1208Dichlobenil 1210Dichlorprop 1212Diclofenac 1214Diclosulam 1218Difloxacin 1220Digoxin 1223Diltiazem 1227Diniconazole-M 1230Dinotefuran 1232Diphenhydramine 1237Dipyridamole 1241Divalproex 1244Domperidone 1249Donepezil 1253Dopamine 1257Doripenem 1260Dorzolamide 1263Doxazosin 1266Doxorubicin 1269Dronabinol 1274Drospirenone 1278Duloxetine 1281Dutasteride 1283Edoxaban 1286Efavirenz 1291Eletriptan 1297Eltrombopag 1299Elzasonan 1302Emtricitabine 1305Enalapril 1308Enfuvirtide 1311Enoxaparin 1315Eplerenone 1318Erdosteine 1322Erlotinib 1324Ertugliflozin 1327Escitalopram 1331Esomeprazole 1335Estazolam 1338Estrogens 1341Ethinylestradiol 1347Ethionamide 1350Ethiprole 1354Ethoxysulfuron 1360Etonogestrel 1362Etoricoxib 1365Etridiazole 1368Exemestane 1370Ezetimibe 1373Ezlopitant 1377Chemical Name Index ICAS Number Index IXVolume 4About the Editors xxxiiiPreface xxxviiList of Data Compilers of Volumes 3–5 xxxixAbbreviations and Acronyms xliFamciclovir 1381Famitinib 1385Famotidine 1391FDDNP 1393Febuxostat 1395Felodipine 1399Fenazaquin 1404Fenofibrate 1406Fenpropimorph 1411Fenproporex 1416Fenpyroximate 1419Fentanyl 1422Fexofenadine 1425Finasteride 1427Fingolimod 1431Flonicamid 1435Fluazinam 1439Fluconazole 1444Flumioxazin 1446Flunarizine 1450Flunitrazepam 1455Fluopicolide 1458Fluoxastrobin 1462Flupyrsulfuron methyl 1467Fluroxypyr 1469Flutamide 1471Fluticasone furoate 1475Fluticasone propionate 1478Fluvastatin 1480Fluvoxamine 1483Forchlorfenuron 1487Fosinopril 1489Furametpyr 1492Gabapentin 1495Galantamine 1497Gambogic acid 1502Ganoderic acid D 1506Garenoxacin 1509Gefitinib 1511Gemfibrozil 1516Gemopatrilat 1522Genipin 1525Glafenine 1527Glatiramer acetate 1531Gliclazide 1533Glipizide 1536Granisetron 1538Harmaline 1541Hexaconazole 1543Hydrochlorothiazide 1546Hydrocodone (oxycodone) 1548Hydroxychavicol 1551Ibandronate 1553Ibuprofen 1555Ilaprazole 1559Iloperidone 1562Imatinib 1567Imazamethabenz-methyl 1571Imazamox 1573Imazosulfuron 1577Imidafenacin 1579Imiprothrin 1582Imiquimod 1584Imrecoxib 1587Indacaterol 1590Indapamide 1593Indinavir 1597Ipconazole 1601Ipratropium 1603Irbesartan 1606Irinotecan 1609Irofulven 1614Isoeugenol 1617Isoxaflutole 1619Isoxicam 1621Ivermectin 1624Ixabepilone 1628Lamivudine 1632Lamotrigine 1634Lansoprazole 1638Lapatinib 1640Laropiprant 1643Lasofoxifene 1647Latanoprost 1651Lefucoxib 1655Lersivirine 1657Letosteine 1660Letrozole 1662Levalbuterol 1665Levocetirizine 1668Levofloxacin 1671Levonorgestrel 1673Levothyroxine 1677Lidocaine 1679Linagliptin 1682Lindane 1685Linezolid 1687Lithocholic acid 1690Lithospermic acid 1693Lopinavir 1696Loratadine 1701Lorazepam 1706Losartan 1710Lovastatin 1715Lufenuron 1719Lumiracoxib 1723Lurasidone 1726Mandipropamid 1732Mebeverine 1738Medroxyprogesterone acetate 1741Meisoindigo 1745Meloxicam 1747Memantine 1752Menadione 1754Mesalamine 1758Mesosulfuron-methyl 1761Mesotrione 1764Metaxalone 1767Metformin 1769Methadone 1771Methoxyfenozide 1775Methyldopa 1780Methylphenidate 1783Metoclopramide 1786Metofluthrin 1790Metoprolol 1792Metoxuron 1795Metronidazole 1797Mexiletine 1800Mianserin 1803Mifepristone 1808Milnacipran 1812Minocycline 1814Mirabegron 1816Misoprostol 1819Modafinil 1821Mometasone furoate 1824Montelukast 1827Moricizine 1830Morinidazole 1833Moxifloxacin 1836Moxonidine 1838Mycophenolate mofetil 1841Nabumetone 1845Naloxone 1847Nateglinide 1850Nevirapine 1853Niacin 1858Nicardipine 1861Nicotine 1865Nifedipine 1870Nilotinib 1874Nilutamide 1878Nimodipine 1881Nizatidine 1885Norelgestromin 1888Norfloxacin 1891Norgestimate 1893Nortriptyline 1897Novaluron 1900Chemical Name Index ICAS Number Index IXVolume 5About the Editors xxxiiiPreface xxxviiList of Data Compilers of Volumes 3–5 xxxixAbbreviations and Acronyms xliOlanzapine 1905Olmesartan medoxomil 1909Olopatadine 1912Omeprazole 1915Ondansetron 1918Ornidazole 1921Orphenadrine 1923Oxadiargyl 1925Oxcarbazepine 1930Oxybenzone 1933Oxycodone 1936Paclitaxel 1940Paclobutrazol 1945Paeonol 1949Paliperidone 1951Pantoprazole 1953Paroxetine 1957Pefloxacin 1960Peliglitazar 1962Penthiopyrad 1965Pentoxazone 1970Perphenazine 1972Phenolphthalein 1976Picolinafen 1978Pindolol 1981Pioglitazone 1984Piperacillin 1988Piroxicam 1991Pirprofen 1993Pitavastatin 1998Pramipexole 2004Pravastatin 2006Prazosin 2012Pregabalin 2016Prochloraz 2018Propafenone 2020Prosulfuron 2024Prothioconazole 202720(S )-Protopanaxadiol 2030Proxyphylline 2033Pseudoephedrine 2035(2S )-Pterosin A 2037Pyraflufen-ethyl 2039Pyrasulfotole 2042Pyrazosulfuron methyl 2045Pyribenzoxim 2047Pyridalyl 2050Pyrimethanil 2055Quetiapine 2058Rabeprazole 2061Raloxifene 2065Ramelteon 2069Ranitidine 2072Repaglinide 2075Rifapentine 2079Risedronate 2082Risperidone 2084Ritonavir 2087Rivaroxaban 2092Rizatriptan 2096Rofecoxib 2100Roflumilast 2105Ropinirole 2107Rosiglitazone 2110Rosuvastatin 2115Rotigotine 2119Ruboxistaurin 2122Rufinamide 2125Ruxolitinib 2127Salmeterol 2130Sameridine 2133Saxagliptin 2136Selegiline 2139Seliciclib 2142Sertraline 2145Silafluofen 2149Sildenafil 2151Simvastatin 2155Sitagliptin 2160Sorafenib 2164Sudoxicam 2166Sulcotrione 2169Sulindac 2172Sumatriptan 2175Sunepitron 2178Tacrolimus 2183Tadalafil 2187Tafluprost 2190Tamoxifen 2193Tamsulosin 2197Telmisartan 2200Temozolomide 2202Tenofovir 2205Tepraloxydim 2208Terazosin 2212Terbinafine 2215Tetraconazole 2219Thalidomide 2222Theophylline 2226Thiamethoxam 2231Ticagrelor 2236Ticlopidine 2239Timolol 2242Tinidazole 2245Tiotropium 2247Tipranavir 2250Tirapazamine 2253Tobramycin 2255Tolbutamide 2257Tolcapone 2261Tolfenpyrad 2265Tolterodine 2267Tolvaptan 2270Topiramate 2274Torcetrapib 2277Tramadol 2281Trandolapril 2284Traxoprodil 2286Triamcinolone 2289Triamcinolone acetonide 2291Triasulfuron 2294Triclosan 2296Trimebutine 2298Tropisetron 2302Vabicaserin 2305Valacyclovir 2310Valdecoxib 2313Valsartan 2317Vardenafil 2319Varenicline 2322Vemurafenib 2325Venlafaxine 2328Verapamil 2332Veratridine 2336Vilanterol 2339Vildagliptin 2343Vinorelbine 2348Vismodegib 2353Warfarin 2357Ximelagatran 2361Zafirlukast 2363Zearalenone 2366Zibotentan 2369Zidovudine 2372Ziprasidone 2375Zofenopril 2382Zolmitriptan 2385Zolpidem 2387Chemical Name Index ICAS Number Index IX

Dr Philip W. Lee, School of Pharmacy, East China University of Science and Technology, Shanghai, Peoples' Republic of China.Dr. Philip W. Lee has more than 35 years of industrial experience in the field of agrochemical research and development. He is currently Professor at School of Pharmacy, East China University of Science and Technology. He has published more than 40 scientific articles in pesticides and drug metabolism and environmental chemistry.Dr. Lee is a contributing editor for the Volume 1 and 2 of the Metabolic Pathways of Agrochemicals, published by Royal Society of Chemistry (RSC) in 1998 and 1999, and is the Editor-in-Chief of a 2-volume Handbook of Residue Analytical Methods for Agrochemicals, published by Wiley in 2003. He is the editor of Pesticide Chemistry: Crop Protection, Public Health and Environmental Safety, conference proceeding book of the 2006 IUPAC International Pesticide Congress, Kobe, Japan, published by Wiley-VCH, 2007.Hiroyasu Aizawa, Hiro Research Consultancy Inc. (HRCI), Toyko, Japan.Lawrence L. Gan, Biogen Idec, Inc., Cambridge, MA, USA.Chandra C. Prakash, Biogen Idec, Inc., Cambridge, MA, USA.Dafang D. Zhong, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, Peoples' Republic of China.Dr. Hiro Aizawa has been active for more than 20 years in the study of animal drug metabolism. Dr Lawrence Gan and Dr. Chandrah Prakash are active with a long experience in the development of human drugs and the study of human drug metabolism.

• Volume 1About the Editors xxxiiiPreface xxxviiList of Contributors of Volumes 1 and 2 xxxixAbbreviations and Acronyms xliA personal and historical perspective on drug metabolism 1Gerald T. Miwa and Arthur K. ChoFundamentals of organic chemistry as applicable to the biotransformation of foreign compounds 27Antonia F. Stepan and Amit S. KalgutkarFunctional group biotransformations 61R. Scott ObachDrugs as victims and perpetrators and the pharmacokinetic concept of maximum exposure 103Brian W. Ogilvie and Andrew ParkinsonDrug-metabolizing enzymes: a group of promiscuous catalysts 125Qiang Ma and Anthony Y.H. LuUnusual metabolic reactions and pathways 147F. Peter Guengerich and Emre M. IsinRole of biotransformation in drug discovery 199Ronald E. WhiteRole of metabolism in drug development 215Role of biotransformation in pesticide discovery and development 233Michael E. Krolski and Stephen C. DacusRole of cytochrome P450 enzymes in biotransformation 249Paul R. Ortiz de MontellanoMajor human conjugative drug-metabolizing enzymes 267Daniel R. Albaugh and Michael B. FisherMetabolic activation and associated drug toxicity 303Thomas A. BaillieIn vitro experimental models for studying drug biotransformation 321Tonika Bohnert and Lawrence L. GanIn vivo experimental models for studying drug biotransformation 383W. Griffith HumphreysVolume 2About the Editors xxxiiiPreface xxxviiList of Contributors of Volumes 1 and 2 xxxixAbbreviations and Acronyms xliTheory and instrumentation of mass spectrometry and its application to drug metabolism 393Stacy L. Gelhaus and Ian A. BlairMass spectral interpretation 419Li-Kang Zhang and Birendra N. PramanikComputational approaches in drug biotransformation studies: metabolite prediction 457Nigel J. Waters and Michelle K. DennehyHigh-throughput metabolite detection and quantitative–qualitative bioanalysis 481Donghui Cui and Sean YuMetabolic stability screen in drug discovery 499Chuang LuApplication of triple-quadrupole and its hybrid mass spectrometers for the identification of drug metabolites 523Zhi-Yi Zhang, Chandra Prakash, and Lin XuRole of ion trap LC-MS techniques for the identification of drug metabolites 553Robert D. Pelletier and W. George LaiDrug metabolite identification with high-resolution mass spectrometry 567Haiying Zhang and Mingshe ZhuStrategies for the identification of unusual and novel metabolites using derivatization, hydrogen–deuterium exchange (HDX), and liquid chromatography-nuclear magnetic resonance (LC-NMR) spectroscopy techniques 591Amin Kamel, Shawn Harriman, and Chandra PrakashThe use of nanoelectrospray mass spectrometry for the quantitation of metabolites in the absence of synthetic standards 619Jing-Tao WuQuantitation of drug metabolites by radioactivity detection including accelerator mass spectrometry (AMS) 633Angus N.R. Nedderman and Mark E. SavageApplication of quantitative NMR in drug metabolism studies 661Abdul E. MutlibEarly assessment of exposure of drug metabolites in humans using mass spectrometry 693Natalia A. Penner, Joanna Zgoda-Pols, and Chandra PrakashProfiling and characterization of bioactive substances of herbal medicine and their metabolites using mass spectrometry 723Xiaoyan ChenApplication of in silico metabolism and environmental degradation data to support chemical PBT assessment 787Sabcho Dimitrov, Gilman Veith, and Ovanes MekenyanVolume 3About the Editors xxxiiiPreface xxxviiList of Data Compilers of Volumes 3–5 xxxixAbbreviations and Acronyms xliAbacavir 809Acebutolol 813Acequinocyl 815Acetaminophen 821Acibenzolar-S -methyl 825Acyclovir 829Adapalene 832Adonifoline 834Albuterol 837Alendronate 840Alfentanil 842Aliskiren 847Alloxan 849Almotriptan 851Alprazolam 856Amantadine 859Ambroxol 861Amiodarone 864Amisulbrom 867Amitriptyline 875Amlodipine 878Amoxicillin 884Amphetamine 887Anastrozole 889trans-Anethole 892Aniracetam 895Antipyrine 898Apixaban 902Apremilast 905Aprepitant 909Aranidipine 913Arbidol 915Aripiprazole 918Asenapine 921Aspirin 924Atazanavir 927Atenolol 931Atomoxetine 933Atorvastatin 937Azelastine 942Barnidipine 945Benazepril 949Bendamustine 952Benfuresate 956Benidipine 959Benthiavalicarb isopropyl 964Benzophenone 969Benzoyl peroxide 972Berberine 974Betaxolol 979Bexarotene 981Bicalutamide 986Bicifadine 990Bimatoprost 994Bisoprolol 996BMS-214778 999Boceprevir 1002Bortezomib 1006Bosentan 1009Brimonidine 1012Brivaracetam 1015Bromhexine 1018Brompheniramine 1024Budesonide 1027Buprenorphine 1030Bupropion 1033Buspirone 1036Butalbital 10413-n-Butylphthalide 1043Caffeine 1047Calcipotriene 1051Candesartan 1054Capecitabine 1057Capravirine 1061Captopril 1067Carazolol 1070Carfilzomib 1072Carvedilol 1076Casopitant 1081Cefdinir 1085Cefepime 1088Celecoxib 1090Cetirizine 1094Chlorpheniramine 1098Chlorpromazine 1102Cholecalciferol 1106Cibenzoline 1110Ciclesonide 1113Cidofovir 1118Cinacalcet 1121Ciprofloxacin 1125Cisapride 1128Cladribine 1136Clebopride 1139Clenbuterol 1142Clindamycin 1145Clobazam 1147Clofarabine 1151Clofibrate 1154Clopidogrel 1156Coumarin 1159Cyclamate 1163Cyclobenzaprine 1165Dabigatran 1170Darifenacin 1174Darunavir 1177Dauricine 1181Degarelix 1186Desloratadine 1190Dexamethasone 1193Dexfenfluramine 1196Dexmethylphenidate 1198Dextroamphetamine 1201Diazepam 1204Diazoxide 1208Dichlobenil 1210Dichlorprop 1212Diclofenac 1214Diclosulam 1218Difloxacin 1220Digoxin 1223Diltiazem 1227Diniconazole-M 1230Dinotefuran 1232Diphenhydramine 1237Dipyridamole 1241Divalproex 1244Domperidone 1249Donepezil 1253Dopamine 1257Doripenem 1260Dorzolamide 1263Doxazosin 1266Doxorubicin 1269Dronabinol 1274Drospirenone 1278Duloxetine 1281Dutasteride 1283Edoxaban 1286Efavirenz 1291Eletriptan 1297Eltrombopag 1299Elzasonan 1302Emtricitabine 1305Enalapril 1308Enfuvirtide 1311Enoxaparin 1315Eplerenone 1318Erdosteine 1322Erlotinib 1324Ertugliflozin 1327Escitalopram 1331Esomeprazole 1335Estazolam 1338Estrogens 1341Ethinylestradiol 1347Ethionamide 1350Ethiprole 1354Ethoxysulfuron 1360Etonogestrel 1362Etoricoxib 1365Etridiazole 1368Exemestane 1370Ezetimibe 1373Ezlopitant 1377Chemical Name Index ICAS Number Index IXVolume 4About the Editors xxxiiiPreface xxxviiList of Data Compilers of Volumes 3–5 xxxixAbbreviations and Acronyms xliFamciclovir 1381Famitinib 1385Famotidine 1391FDDNP 1393Febuxostat 1395Felodipine 1399Fenazaquin 1404Fenofibrate 1406Fenpropimorph 1411Fenproporex 1416Fenpyroximate 1419Fentanyl 1422Fexofenadine 1425Finasteride 1427Fingolimod 1431Flonicamid 1435Fluazinam 1439Fluconazole 1444Flumioxazin 1446Flunarizine 1450Flunitrazepam 1455Fluopicolide 1458Fluoxastrobin 1462Flupyrsulfuron methyl 1467Fluroxypyr 1469Flutamide 1471Fluticasone furoate 1475Fluticasone propionate 1478Fluvastatin 1480Fluvoxamine 1483Forchlorfenuron 1487Fosinopril 1489Furametpyr 1492Gabapentin 1495Galantamine 1497Gambogic acid 1502Ganoderic acid D 1506Garenoxacin 1509Gefitinib 1511Gemfibrozil 1516Gemopatrilat 1522Genipin 1525Glafenine 1527Glatiramer acetate 1531Gliclazide 1533Glipizide 1536Granisetron 1538Harmaline 1541Hexaconazole 1543Hydrochlorothiazide 1546Hydrocodone (oxycodone) 1548Hydroxychavicol 1551Ibandronate 1553Ibuprofen 1555Ilaprazole 1559Iloperidone 1562Imatinib 1567Imazamethabenz-methyl 1571Imazamox 1573Imazosulfuron 1577Imidafenacin 1579Imiprothrin 1582Imiquimod 1584Imrecoxib 1587Indacaterol 1590Indapamide 1593Indinavir 1597Ipconazole 1601Ipratropium 1603Irbesartan 1606Irinotecan 1609Irofulven 1614Isoeugenol 1617Isoxaflutole 1619Isoxicam 1621Ivermectin 1624Ixabepilone 1628Lamivudine 1632Lamotrigine 1634Lansoprazole 1638Lapatinib 1640Laropiprant 1643Lasofoxifene 1647Latanoprost 1651Lefucoxib 1655Lersivirine 1657Letosteine 1660Letrozole 1662Levalbuterol 1665Levocetirizine 1668Levofloxacin 1671Levonorgestrel 1673Levothyroxine 1677Lidocaine 1679Linagliptin 1682Lindane 1685Linezolid 1687Lithocholic acid 1690Lithospermic acid 1693Lopinavir 1696Loratadine 1701Lorazepam 1706Losartan 1710Lovastatin 1715Lufenuron 1719Lumiracoxib 1723Lurasidone 1726Mandipropamid 1732Mebeverine 1738Medroxyprogesterone acetate 1741Meisoindigo 1745Meloxicam 1747Memantine 1752Menadione 1754Mesalamine 1758Mesosulfuron-methyl 1761Mesotrione 1764Metaxalone 1767Metformin 1769Methadone 1771Methoxyfenozide 1775Methyldopa 1780Methylphenidate 1783Metoclopramide 1786Metofluthrin 1790Metoprolol 1792Metoxuron 1795Metronidazole 1797Mexiletine 1800Mianserin 1803Mifepristone 1808Milnacipran 1812Minocycline 1814Mirabegron 1816Misoprostol 1819Modafinil 1821Mometasone furoate 1824Montelukast 1827Moricizine 1830Morinidazole 1833Moxifloxacin 1836Moxonidine 1838Mycophenolate mofetil 1841Nabumetone 1845Naloxone 1847Nateglinide 1850Nevirapine 1853Niacin 1858Nicardipine 1861Nicotine 1865Nifedipine 1870Nilotinib 1874Nilutamide 1878Nimodipine 1881Nizatidine 1885Norelgestromin 1888Norfloxacin 1891Norgestimate 1893Nortriptyline 1897Novaluron 1900Chemical Name Index ICAS Number Index IXVolume 5About the Editors xxxiiiPreface xxxviiList of Data Compilers of Volumes 3–5 xxxixAbbreviations and Acronyms xliOlanzapine 1905Olmesartan medoxomil 1909Olopatadine 1912Omeprazole 1915Ondansetron 1918Ornidazole 1921Orphenadrine 1923Oxadiargyl 1925Oxcarbazepine 1930Oxybenzone 1933Oxycodone 1936Paclitaxel 1940Paclobutrazol 1945Paeonol 1949Paliperidone 1951Pantoprazole 1953Paroxetine 1957Pefloxacin 1960Peliglitazar 1962Penthiopyrad 1965Pentoxazone 1970Perphenazine 1972Phenolphthalein 1976Picolinafen 1978Pindolol 1981Pioglitazone 1984Piperacillin 1988Piroxicam 1991Pirprofen 1993Pitavastatin 1998Pramipexole 2004Pravastatin 2006Prazosin 2012Pregabalin 2016Prochloraz 2018Propafenone 2020Prosulfuron 2024Prothioconazole 202720(S )-Protopanaxadiol 2030Proxyphylline 2033Pseudoephedrine 2035(2S )-Pterosin A 2037Pyraflufen-ethyl 2039Pyrasulfotole 2042Pyrazosulfuron methyl 2045Pyribenzoxim 2047Pyridalyl 2050Pyrimethanil 2055Quetiapine 2058Rabeprazole 2061Raloxifene 2065Ramelteon 2069Ranitidine 2072Repaglinide 2075Rifapentine 2079Risedronate 2082Risperidone 2084Ritonavir 2087Rivaroxaban 2092Rizatriptan 2096Rofecoxib 2100Roflumilast 2105Ropinirole 2107Rosiglitazone 2110Rosuvastatin 2115Rotigotine 2119Ruboxistaurin 2122Rufinamide 2125Ruxolitinib 2127Salmeterol 2130Sameridine 2133Saxagliptin 2136Selegiline 2139Seliciclib 2142Sertraline 2145Silafluofen 2149Sildenafil 2151Simvastatin 2155Sitagliptin 2160Sorafenib 2164Sudoxicam 2166Sulcotrione 2169Sulindac 2172Sumatriptan 2175Sunepitron 2178Tacrolimus 2183Tadalafil 2187Tafluprost 2190Tamoxifen 2193Tamsulosin 2197Telmisartan 2200Temozolomide 2202Tenofovir 2205Tepraloxydim 2208Terazosin 2212Terbinafine 2215Tetraconazole 2219Thalidomide 2222Theophylline 2226Thiamethoxam 2231Ticagrelor 2236Ticlopidine 2239Timolol 2242Tinidazole 2245Tiotropium 2247Tipranavir 2250Tirapazamine 2253Tobramycin 2255Tolbutamide 2257Tolcapone 2261Tolfenpyrad 2265Tolterodine 2267Tolvaptan 2270Topiramate 2274Torcetrapib 2277Tramadol 2281Trandolapril 2284Traxoprodil 2286Triamcinolone 2289Triamcinolone acetonide 2291Triasulfuron 2294Triclosan 2296Trimebutine 2298Tropisetron 2302Vabicaserin 2305Valacyclovir 2310Valdecoxib 2313Valsartan 2317Vardenafil 2319Varenicline 2322Vemurafenib 2325Venlafaxine 2328Verapamil 2332Veratridine 2336Vilanterol 2339Vildagliptin 2343Vinorelbine 2348Vismodegib 2353Warfarin 2357Ximelagatran 2361Zafirlukast 2363Zearalenone 2366Zibotentan 2369Zidovudine 2372Ziprasidone 2375Zofenopril 2382Zolmitriptan 2385Zolpidem 2387Chemical Name Index ICAS Number Index IX