APPENDIX H

pKa's OF DRUGS AND REFERENCE COMPOUNDS

Name pKa Reference Name Amobarbital Amoxicillin pKa 8.0 2.4 (carboxyl) 7.4 (amine) 9.6 (phenol) 9.8 5.7 (carboxyl) 10.0 (amine) 2.7 7.3 (amine) 3.7 7.5 4.6 4.1 10.0 7.2 1.4 2.2 1.4 7.0 8.9 7.8 7.6 9.5 (phenol) 4.2 11.6 3.5 9.7 Reference 22 23

A
Acenocoumarol Acetaminophen Acetanilid Acetarsone 4.7 9.9 (phenol) 0.5 3.7 (acid) 7.9 (phenol) 9.3 (acid) 8.8 (acetamido) 7.2 4.8 8.3 9.3 6.1 5.2 6.9 8.2 4.4 8.2 9.3 10.3 7.5 9.4 10.7 7.6 8.7 9.6 8.7 10.8 2.4 (amine) 4.9 4.4 10.8 3.6 2.3 (carboxyl) 4.9 (amine) 5.0 5.5 (heterocyclic ring) 5.0 1.7 (amine) 3.9 9.4 9.3 1 2 3 4

Amphetamine Amphotericin B Ampicillin Anileridine Aniline Anisindione Antazoline Antifebrin Antipyrine Apomorphine Aprobarbital Arecoline Arsthinol Ascorbic Acid Aspirin Atropine

24 25 26 16 6 27 28 16 29 29 29 30 32 10 31 4 18 7 30

Acetazolamide Acetic Acid "-Acetylmethodol Acetylpromazine N4 -Acetylsulfadiazine N4 -Acetylsulfametiazole N4 -Acetylsulfamethoxypyridazine N4 -Acetylsulfapyridine N4 -Acetylsulfisoxazole Adriamycin Albuterol Allobarbital Allopurinol Allylamine Allybarbituric Acid Alphaprodine Alprenolol Amiloride Amantadine p-Aminobenzoic Acid Aminocaproic Acid Aminohippuric acid 6-Aminopenicillanic Acid Aminophylline Aminopterin Aminopyrine Aminosalicylic Acid Amitriptyline Ammonia

5 40 6 7 8 9 9 9 9 9 41 30 10 11 12 13 14 15 15 16 17 18 15 19 42 20 6 17 21 12

B
Barbital Barbituric Acid Bemegride Bendroflumethiazide Benzilic Acid Benzocaine Benzoic Acid Benzphetamine Benzquinamide Benzylamine Betahistine Bethanidine 7.8 4.0 11.2 8.5 3.0 2.8 4.2 6.6 5.9 9.3 3.5 9.7 10.6 32 32 33 34 12 30 7 35 36 12 29 52

Name Biscoumacetic Acid Bromazepam Bromodiphenhydramine p-Bromophenol Bromothen 8-Bromotheophylline Brucine Bupivacaine Burimamide Butabarbital Butethal Butylparaben Butyric Acid

pKa 3.1 7.8 (enol) 11.0 2.9 8.6 9.2 8.6 5.5 8.0 8.1 7.5 7.9 8.1 8.4 4.8

Reference 1 174 53 37 38 28 13 6 39 29 15 40 41 12

Name Chlorambucil Chlorcyclizine Chlordiazepoxide Chlorindione Chlormethiazole Chloroquine Chlorothen 8-Chlorotheophylline Chlorothiazide Chlorpheniramine Chlorphentermine Chlorpromazine Chlorpromazine Sulfoxide Chlorpropamide Chlorprothixene Chlortetracycline

pKa 5.8 7.8 8.2 4.8 3.6 3.2 8.1 9.9 8.4 5.3 8.2 6.7 9.5 9.2 9.6 9.2 9.0 5.0 8.4 3.3 7.4 9.3 9.4 8.3 6.8 4.2 (1st) 8.4 (2nd) 4.0 (1st) 8.2 (2nd) 4.5 3.1 (1st) 4.8 (2nd) 6.4 (3rd) 7.5 3.0 (acid) 10.5 (1-position) 1.5 (4-position) 8.0 2.7 8.5 8.4 7.9 1.7 10.3 10.1

Reference 48 37 59 49 27 30 50 54 51 60 52 37 35 53 44 54 55 56

C
Caffeine Camphoric Acid Capreomycin 14.0 0.6 (amine) 4.7 6.2 8.2 10.1 13.3 4.8 2.6 2.7 6.7 7.1 8.1 6.4 (1st) 10.4 (2nd) 2.3 3.6 5.25 7.1 2.5 4.6 7.1 3.4 2.4 2.2 2.6 (carboxyl) 7.3 (amine) 10.0 42 12 32

Carbachol Carbenicillin Carbenoxolone Carbinoxamine Carbonic Acid Cefazolin Cephalexin

16 29 30 43 6 44 45 36 45 56 46 45 15 47 34

Chlorthalidone Chlorzoxazone Cimetidine Cinchonidine Cinchonine Cinnamic Acid Citric Acid

42 15 115 3 30 12 57

Clindamycin Clofibrate Clonazepam Clonidine Cloxacillin Cobefrin Cocaine Codeine Colchicine o-Cresol m-Cresol

58 15 59 60 19 24 3 42 18 17 17

Cephaloglycin L-Cephaloglycin Cephaloridine Cephalothin Cephapirin Cephradine Chloral Hydrate

Name p-Cresol Cromolyn Cyanic Acid Cyanopromazine Cyclizine Cyclobarbital Cyclopentamine Cyclopentolate Cycloserine Cyclothiazide Cytarabine

pKa 10.3 2.0 3.8 9.3 8.2 7.5 3.5 11.5 7.9 4.5 7.4 9.1 10.5 4.3

Reference 61 30 12 62 63 8 64 50 65 16 33 30

Name p-Diethylaminosalicylic Acid Dihydrocodeine Dihydroergocornine Dihydroergocriptine Dihydroergocristine Dihydroergotamine Dihydroergotamine mesylate Dihydrostreptomycin 3,5-Diiodo-L-Tyrosine

pKa 3.8 8.8 6.9 6.9 6.9 6.9 8.0 7.8 2.5 (amine) 6.5 7.5 (phenol) 10.7 5.1 3.8 7.1 8.1 4.1 4.9 8.4 9.0 7.1 4.4 6.4 8.4 8.0 8.2 10.2 3.4 7.7 9.3 9.2 7.6

Reference 73 3 69 69 69 69 16 15 32

D
Dacarbazine Dantrolene Dapsone Daunomycin Debrisoquin Dehydrocholic Acid Demeclocycline 4.4 7.5 1.3 2.5 8.2 11.9 5.0 3.3 7.2 9.3 6.7 10.2 8.3 7.0 12.1 3.4 3.3 8.5 8.5 7.4 8.6 1.3 2.8 4.4 (1st) 8.0 (2nd) 8.9 11.0 6.2 42 66 50 41 67 68 56

Dimenhydrinate Dimethylamine p-Dimethylaminobenzoic Acid p-Dimethylaminosalicylic Acid Dimethylbarbituric Acid Dimethylhydantoin 2,4-Dinitrophenol Dinoprost Diperodon Diphenhydramine Diphenoxylate Dipyridamole Disopyramide Doxepin Doxorubicin Doxycycline

35, 60 12 73 73 12 3 74 116 75 37 76 60 16 117 42 77 78

Deserpidine Desipramine Dextromethorphan Dextromoramide Dextrose Diatrizoic Acid Diazepam Diazoxide Dibucaine Dichlorphenamide Dichloroacetic Acid Dicloxacillin Dicumarol Diethanolamine Diethylamine p-Diethylaminobenzoic Acid

32 21 43 29 23 69 49 42 70 42 42 26 71 72 12 73

Doxylamine Droperidol

37 79

E
Emetine Ephedrine Epinephrine Equilenin Ergometrine Ergonovine Ergotamine 8.2 7.4 9.6 8.7 (phenol) 9.9 (amine) 9.8 7.3 6.8 6.3 7.3 32 7 80 61 29 11 81 29

Name Erythromycin Erythromycin Estolate 17"-Estradiol Estriol Ethacrynic Acid Ethambutol Ethanolamine Ethoheptazine citrate Ethopropazine Ethosuximide p-Ethoxybenzoic Acid p-Ethoxysalicylic Acid Ethoxazolamide Ethylamine Ethylbarbituric Acid Ethyl Biscoumacetate Ethylenediamine Ethylmorphine Ethylparaben Ethylphenylhydantoin Etidocaine -Eucaine

pKa 8.8 6.9 10.7 10.4 3.5 6.6 9.5 9.5 8.5 9.6 9.3 4.5 3.2 8.1 10.7 4.4 3.1 6.8 (1st) 9.9 (2nd) 7.9 8.4 8.5 7.7 9.4

Reference 82 83 61 61 18 84 72 73 28 15 73 73 42 12 12 1 72 16 41 85 39 3

Name Flurazepam Formic Acid Fumaric Acid Furaltadone Furosemide Fusidic Acid

pKa 8.2 1.9 3.7 3.0 (1st) 4.4 (2nd) 5.0 4.7 3.9 5.4

Reference 90 12 42 91 92 76 32

G
Gallic Acid Gentamicin Glibenclamide Gluconic Acid Glucuronic Acid Glutamic Acid Glutarimide Glutethimide Glyburide Glycerophosphoric Acid Glycine Glycollic Acid Guanethidine Guanidine Guanoxan 4.2 8.2 6.5 3.6 3.2 4.3 11.4 11.8 4.5 5.3 1.5 (1st) 6.2 (2nd) 2.4 9.8 (amine) 3.8 11.9 13.6 12.3 38 77 54 18 93 12 16 94 37 30 42 42 12 67 3 52

F
Fenfluramine Fenoprofen Flucloxacillin Flucytosine Flufenamic Acid Flumizole Flunitrazepam p-Fluorobenzoic Acid Fluorouracil Fluopromazine Fluorouracil Fluphenazine 9.1 4.5 2.7 10.7 (amide) 2.9 (amine) 3.9 10.7 1.8 4.2 8.0 13.0 9.2 8.0 13.0 8.1 (1st) 9.9 (2nd) 3.9 3.5 8.2 35 86 30 87 74 75 59 38 88 61 34 53 34 89

H
Haloperidol Heroin Hexachlorophene Hexetidine Hexobarbital Hexylcaine Hippuric Acid Histamine Homatropine Hydantoin Hydralazine 8.3 7.8 5.7 8.3 8.3 9.1 3.6 9.9 (side chain) 6.0 (imidazole) 9.7 9.1 0.5 (ring N) 6.9 (hydrazine) 95 14 74 96 85 70 97 98 3 17 99

Fluphenazine Enanthate

Name Hydrochlorothiazide Hydrocodone Hydrocortisone Hemisuccinate Acid Hydroflumethiazide Hydrogen Peroxide Hydromorphine Hydromorphone Hydroxyamphetamine p-Hydroxybenzoic Acid o-Hydroxycinnamic Acid m-Hydroxycinnamic Acid p-Hydroxycinnamic Acid Hydroxylamine p-Hydroxysalicylic Acid Hydroxyzine

pKa 7.0 9.2 8.9 5.1 8.9 10.5 11.3 7.8 8.2 9.6 4.1 4.7 4.5 4.4 6.0 3.2 1.8 2.1 7.1 9.3

Reference 18 16 100 101 12 3 73 24 38 38 38 38 6 73 102 81, 82 16

Name

pKa

Reference

K
Kanamycin Ketamine 7.2 7.5 15 110

L
Lactic Acid Leucovorin 3.9 3.1 4.8 10.4 (phenol) 6.9 4.5 8.7 (phenol) 9.7 (amine) 8.72(OH) >12(OH) 2.3 (carboxyl) 8.7 (amine) 9.7 (1st phenol) 13.4 (2nd phenol) 2.31(COOH) 9.74(OH) 13.40(OH) 9.2 8.9 2.2(COOH) 6.7(OH) 10.1 4.6 7.9 7.5 8.4 (phenol) 11.5 1.3 6.6 18 18

Levallorphan Tartrate Levarterenol Levarterenol Bitartrate Levodopa

111 34 112 33 113 113 37

Hyoscyamine

Levodopa

I
Ibuprofen Idoxuridine Imidazole Imipramine Indomethacin Indoprofen Indoramin Iodipamide Iophenoxic Acid Iprindole Isocarboxazid Isomethadone Isoniazid 5.2 8.3 7.0 9.5 4.5 5.8 7.7 3.5 7.5 8.2 10.4 8.1 10.8 (pyridine) 11.2 (hydrazide) 2.0 3.9 3.6 8.7 (amine) 9.9 (phenol) 9.8 8.0 103 104 72 21 18 105 29 106 1 29 107 14 108 84 12 109 30 Levomepromazine Levorphanol Levothyroxine

64 14 37

Levulinic Acid Lidocaine Lincomycin Liothyronine Lorazepam Loxapine

12 114 115 116 117 42

M
Malamic Acid Maleic Acid Malic Acid Malonic Acid Mandelic Acid Mecamylamine 3.6 1.9 3.5 (1st) 5.1 (2nd) 2.8 3.8 3.4 11.2 12 12 57 12 97 32 7

Isophthalic Acid Isoproterenol Isoxsuprine

Name Meclizine Medazepam Mefenamic Acid Mepazine Meperidine Mephentermine Mephenytoin Mephobarbital Mepivacaine Mercaptomerin Mercaptopurine Metaproterenol Metaraminol Methacycline

pKa 3.1 6.2 6.2 4.4 4.3 9.3 8.7 10.3 8.1 7.7 7.6 3.7 5.1 7.8 8.8 11.8 8.6 3.5 7.6 9.2 8.3 9.5 3.7 8.9 (side chain) 2.5 8.2 7.3 7.5 4.9 2.8 2.3 9.2 8.3 9.4 4.8 5.5 3.8 9.2 9.2 3.5 4.2 4.2 4.7 4.5 4.9

Reference 118 119 7 74 53 14 35 120 85 39 42 121 15 30 29 15

Name Methyclothiazide Methylamine 1-Methylbarbituric Acid Methyldopa

pKa 9.4 10.6 4.4 2.2 10.6 (amine) 9.2 (1st phenol) 12.0 (2nd phenol) 9.3 6.7 9.2 10.5 8.4 8.8 2.6 6.0 9.4 12.0 6.6 9.7 8.1 9.7 2.6 6.9 2.8 5.0 7.8 9.5 6.9 2.9 8.0 9.6 (phenol)

Reference 125 12 17 126

N-Methylephedrine Methylergonovine N-Methylglucamine Methylhexylamine Methylparaben Methylphenidate Methylprednisolone-21-phosphate Methylpromazine Methyprylon Methysergide Metolazone Metopon Metoprolol Metronidazole Miconazole Minocycline

127 81 126 64 41 128 129 62 130 81 42 14 15 131 132 15

Methadone Methamphetamine Methapyrilene Methaqualone Metharbital Methazolamide Methdilazine Methenamine Methicillin L-Methionine Methohexital Methopromazine Methotrexate

14 43 3 122 85 18 15 29 19 32 123 62 124 37 50 64 12 38 38 38 38 38

Molindone Monochloroacetic Acid Morphine

133 42 32

N
Nafcillin Nalidixic Acid Nalorphine Naloxone Naphazoline 1-Naphthol 2-Naphthol Naproxen Narcotine Neostigmine 2.7 6.0 (amine) 1.0 7.8 7.9 3.9 10.1 9.2 9.4 4.2 5.9 12.0 26 134 14 42 64 50 38 38 135 3 94

Methotrimeprazine Methoxamine Methoxyacetic Acid o-Methoxybenzoic Acid m-Methoxybenzoic Acid o-Methoxycinnamic Acid m-Methoxycinnamic Acid p-Methoxycinnamic Acid

Name Nicotinamide Nicotine Nicotine Methiodide Nicotinic Acid Nitrazepam o-Nitrobenzoic Acid m-Nitrobenzoic Acid p-Nitrobenzoic Acid Nitrofurantoin Nitrofurazone Nitromethane o-Nitrophenol m-Nitrophenol p-Nitrophenol 8-Nitrotheophylline Nordefrin Norhexobarbital Norketamine Norparamethadione Nortrimethadione Nortriptyline Noscapine Novobiocin

pKa 0.5 3.4 3.1 8.0 3.2 4.8 10.8 3.2 3.2 3.6 3.7 7.2 10.0 11.0 7.2 8.3 7.1 2.1 8.5 7.9 6.7 6.1 6.2 9.7 6.2 4.3 9.1

Reference 11 136 136 18 117 38 38 38 91 137 12 38 38 38 51 72 123 110 85 85 42 18 18

Name

pKa

Reference

P
Pamaquine Papaverine Pargyline Penicillamine 8.7 5.9 6.9 1.8 (carboxyl) 7.9 (amino) 10.5 (thiol) 2.8 2.7 5.2 4.8 8.8 8.0 7.8 3.7 2.2 6.9 8.5 7.6 2.7 11.8 3.1 8.3 4.1 9.3 8.5 7.5 9.9 9.7 7.9 6.9 3.1 10.1 7.7 4.4 5.5 9.8 (amine) 8.8 (phenol) 9.8 9.4 9.9 9.1 5.9 8.3 3.8 3 42 15 18

Penicillin G Penicillin V Penicilloic Acid Pentachlorophenol Pentazocine Pentobarbital Perphenazine Phenacetin Phenadoxane Phenazocine Phendimetrazine Phenethicillin Phenformin Phenindamine Phenindione Pheniramine Phenmetrazine Phenobarbital Phenol Phenolphthalein Phenolsulfonphthalein Phenoxypropazine Phenoxyacetic Acid Phentermine Phentolamine Phenylbutazone Phenylbutazone (isopropyl analog) Phenylephrine Phenylethylamine Phenylpropanolamine Phenylpropylmethylamine Phenyltoloxamine Phenyramidol Phenytoin o-Phthalamic Acid

O
Ornidazole Orphenadrine Oxacillin Oxamic Acid Oxazepam Oxycodone Oxymorphone Oxyphenbutazone Oxypurinol Oxytetracycline 2.6 8.4 2.8 2.1 1.8 11.1 8.9 9.3 8.5 4.5 10.0 (phenol) 7.7 3.3 7.3 9.1 131 15 85 12 138 16 16 93 42 56

42 19 139 74 73 32 21 60 29 14 73 35 19 140 36 37 27 37 35 13 7 16 18 16 12 35 16 141 142 143 24 109 24 16 18 144 12

Name Phthalic Acid Phthalimide Physostigmine Picolinic Acid Picric Acid Pilocarpine Pimozide Pindolol Piperazine Piperidine Pirbuterol

pKa 2.9 7.4 2.0 8.1 5.3 0.4 1.6 7.1 7.3 8.8 5.7 10.0 11.2 3.0 (pyridine) 7.0 (pyridol) 10.3 (amine) 3.5 10.1 8.9 8.9 9.5 3.0 6.5 7.9 8.0 3.4 9.2 9.0 6.8 3.6 7.5 9.4 9.1 2.7 6.6 4.9 8.6 6.3 9.5 10.6 10.6 10.5 8.4 7.8 9.9

Reference 6 12 3 38 42 3 32 30 30 6 145

Name Pyrathiazine Pyrazinamide Pyridine Pyridoxine

pKa 8.9 0.5 5.2 2.7 5.0 (amine) 9.0 (phenol) 4.0 8.9 7.2 9.4 8.8 2.5

Reference 64 18 6 153 153 154 3 1 53 37 18

Pyrilamine Pyrimethamine Pyrimethazine Pyrrobutamine Pyruvic Acid

Q
Quinacrine Quinethazone Quinidine Quinine 8.0 10.2 9.3 10.7 4.2 8.3 4.2 8.8 3 42 3 3

Plasmoquin Polymyxin Polymyxine B Practolol Prazepam Prazosin Prilocaine Probarbital Probenecid Procainamide Procaine Procarbazine Prochlorperazine Promazine Promethazine Propicillin Propiomazine Propionic Acid Propoxycaine Propoxyphene Propranolol i-Propylamine n-Propylamine Propylhexedrine Propylparaben Propylthiouracil Pseudoephedrine

146 30 15 30 147 42 39 22 1 148 149 150 64 53 64 19 151 42 15 73 15 12 12 64 41 152 35

R
Reserpine Resorcinol Riboflavin Rifampin Rolitetracycline 6.6 6.2 1.7 10.2 1.7 (C-8 phenol) 7.9 (piperazine N) 7.4 42 12 3 155 30

S
Saccharic Acid Saccharin Salicylamide Salicylic Acid Scopolamine Secobarbital Serotonin Sorbic Acid 3.0 1.6 8.1 3.0 13.4 (phenol) 7.6 8.0 12.6 4.9 9.8 4.8 12 42 32 6 3 156 33 18 12

Name Sotalol Spectinomycin Strychnine Succinic Acid Succinimide Succinuric Acid Succinylsulfathiazole Sulfacetamide Sulfadiazine Sulfadimethoxine Sulfadimethoxytriazine Sulfaethidole Sulfaguanidine Sulfamerazine Sulfameter Sulfamethazine Sulfamethizole Sulfamethoxazole Sulfamethoxypyridazine Sulfanilamide Sulfanilic Acid Sulfaphenazole Sulfapyridine Sulfasalazine

pKa 9.8 (amine) 8.3 (sulfonamide) 7.0 8.7 2.5 8.2 4.2 (1st) 5.6 (2nd) 9.6 4.5 4.5 5.4 1.8 6.5 2.0 6.7 2.0 (amine) 5.0 5.4 1.9 2.8 12.1 7.1 2.3 6.8 7.4 2.4 5.4 2.0 5.6 7.2 10.4 3.2 6.5 1.9 (amine) 8.4 2.6 0.6 (amine) 2.4 (carboxyl) 9.7 (sulfonamide) 11.8 (phenol) 7.1 2.4 2.8 7.5

Reference 157 18 3

Name Sulfisoxazole

pKa 2.4 (amine) 5.0

Reference 32

T
Talbutal Tartaric Acid Terbutaline 7.8 3.0 (1st) 4.3 (2nd) 10.1 11.2 8.8 8.5 3.3 7.7 9.5 3.9 8.9 8.8 0.7 (amine) 10.1 0.1 8.8 0.7 (amine) 3.5 9.1 4.8 9.0 7.3 3.3 3.6 7.5 3.2 7.2 9.5 7.5 8.8 2.2 9.6 (phenol) 2.2 (carboxyl) 6.7 (phenol) 10.1 (amine) 2.6 3.4 5.7 3.1 10.3 10 57 15

158 12 15 159 32 88 159 9 32 88 32 88 42 88 18 32 88 32 88 34 9 160 6 159 42 88 161

Tetracaine Tetracycline

70 56

Thenyldiamine Theobromine

3 32 32 32 36 15 153 123 12 12 123 64 53 152 37 50 116 162

Theophylline

Theophylline Ethanolamine Thiamine Thiamylal Thioacetic Acid Thioglycolic Acid Thiopental Thiopropazate Thioridazine Thiouracil Thonzylamine L-Thyronine L-Thyroxine

Ticarcillin 42 88 93 159 Tolazamide Tolazoline

42 15 30 163

Sulfathiazole Sulfinpyrazone Sulfisomidine

Name Tolbutamide Tolmetin p-Toluidine Tranexamic Acid Tranylcypromine Triamterene Trichlormethiazide Trichloroacetic Acid Triethanolamine Triethylamine Trifluoperazine Triflupromazine Trimethobenzamide Trimethoprim Trimethylamine Tripelennamine Triprolidine Troleandomycin Tromethamine Tropacocaine Tropic Acid Tropicamide Tropine Tuaminoheptane Tubocurarine Tubocurarine Chloride Tyramine

pKa 5.3 3.5 5.3 4.3 10.6 8.2 6.2 8.6 0.9 7.8 10.7 4.1 8.4 9.4 8.3 7.2 9.8 9.0 4.2 6.5 6.6 8.1 9.7 4.1 5.2 10.4 10.5 8.1 9.1 7.4 9.5 (phenol) 10.8 (amine)

Reference 32 42 7 29 16 16 42 42 72 29 53 64 164 165 12 37 50 166 18 72 30 12 167 12 50 59 168 109

Name

pKa 7.4 5.0 7.4 8.2 10.3 12.0

Reference

Vincristine Viomycin

33 18

W
Warfarin 5.1 172

X
Xipamide 4.8 (phenol) 10.0 (sulfonamide) 173

U
Urea Uric Acid 0.2 5.4 10.3 169 170

V
Valeric Acid Vanillic Acid Vanillin Vinbarbital Vinblastine 4.8 4.5 7.4 8.0 5.4 42 12 17 22 171

REFERENCES 1. 2. 3. 4. 5. 6. 7. 8. 9. 10. 11. 12. 13. 14. 15. 16. 17. 18. 19. 20. 21. 22. 23. 24. 25. 26. 27. 28. 29. 30. 31. 32. 33. 34. 35. 36. 37. 38. 39. 40. 41. 42. 43. 44. 45. 46. 47. 48. 49. 50. 51. 52. 53. 54. 55. 56. 57. 58. 59. 60. 61. 62. 63. 64. Anton AH. J Pharmacol Exp Ther. 1961; 134:291. Rhodes HJ, et al. J Pharm Sci. 1975; 64:1387. Perrin DD. Dissociation Constants of Organic Bases, London, Butterworths, 1965. Hiskey CF, Cantwell FF. J Pharm Sci. 1968; 57:2105. Coleman JE. Ann Rev Pharmacol. 1975; 15:238. Kolthoff IM, Stenger VA. Volumetric Analysis, vol. 1, ed. 2, New York, Interscience Publishers, Inc. 1942. Schanker LS, et al. J Pharmacol Exp Ther. 1957; 120:528. Liu S, Hurwitz A. J Colloid Interface Sci. 1977; 60:410, through Chem Abstr. 1977; 87:44189u. Scudi JW, Plekss OJ. Pro Soc Exptl Biol Med. 1958; 97:639. Carstensen JT, et al. J Pharm Sci. 1964; 53:1547. Gressel PD, Gallelli SF. J Pharm Sci. 1968; 57:335. Washburn EW (ed. in chief), International Critical Tables, New York, McGraw-Hill, 1929; 6:261. Maulding HV, Zoglio MA. J Pharm Sci. 1971; 60:311. Beckett AH. J Pharm Pharmacol. 1956; 8:851. Heel RC, Avery GS, in Avery GS (ed.): Drug Treatment, ed. 2, p. 1212-1222, Sidney, ADIS, 1980. Albert A. Selective Toxicity, ed. 4, p. 281, London, Methuen, 1968. Kortm G, et al. Dissociation Constants of Organic Acids, London, Butterworths, 1961. Windholz M (ed). The Merck Index, 9th ed., Rahway, NJ, Merck & Co., 1976. Rapson HDC, Bird AE. J Pharm Pharmacol. 1963; 15:226T. Baker RB, Jordan JH. J Pharm Sci. 1965; 54:1741. Green AL. J Pharm Pharmacol. 1967; 19:10. Krahl ME. J Phys Chem. 1940; 44:449. Rolinson GN. J Infect Dis. 1974; 129:S143. Leffler EB, et al. J Am Chem Soc. 1951; 73:2611. Asher IM, et al. Analyt Profiles. 1977; 6:11. Hou JP, Poole JW. J Pharm Sci. 1969; 58:1150. Stella VJ, Gish R. J Pharm Sci. 1979; 68:1047. Marshall PB. Brit J Pharmacol. 1955; 10:270. Evstratova KI, et al. Farmatsiya. 1968; 17:33 through Chem Abstr. 1968; 69:9938a. Kolthoff JM. Biochem Z. 1925; 162:289 through Trans Farady Soc. 1945; 39:338. Burgen ASV. J Pharm Pharmacol. 1964; 16:638. Ballard BB, Nelson E. J Pharmacol Exp Ther. 1962; 135:120. Peinhardt G. Pharmazie 1977; 32:725 through Chem Abstr. 1978; 88:141587a. Agren A, Bck T. Acta Pharm Suec. 1973; 10:225. Vree TB, et al. J Pharm Pharmacol. 1969; 21:774. Wiseman EH, et al. Biochem Pharmacol. 1964; 13:1421. Lordi NG, Christian JE. J Am Pharm A. 1956; 45:300. Conners KA, Lipari JM. J Pharm Sci. 1976; 65:380. de Jong RH. J Am Med Assoc. 1977; 238:1284. Fincher JH, et al. J Pharm Sci. 1966; 55:24. Tammilehto S, Bchi J. Pharmac Acta Helvet. 1968; 43:726. Martin AN, et al. Physical Pharmacy, ed. 2, p. 194, Philadelphia, Lea & Febiger, 1969. Borodkin S, Yunker MH. J Pharm Sci. 1970; 59:481. Nightengale CH, et al. J Pharm Sci. 1975; 64:1907. Streng WH. J Pharm Sci. 1978; 67:667. Flynn EH (ed.): Cephalosporins and Penicillins, New York, Academic Press, p. 316, 1972. Florey K. Analyt Profiles. 1976; 5:36. Linford JH. Biochem Pharmacol. 1963; 12:321. Van der Kleijn E. Arch Int Pharmacodyn. 1969; 179:242. Hong PD. Analyt Profiles. 1976; 5:69. Meyer MC, Guttman DE. J Pharm Sci. 1968; 57:245. Resetarits DE, Bates TR. J Pharm Sci. 1979; 68:126. Sorby DL, et al. J Pharm Sci. 1966; 58:788. Crooks MJ, Brown KF. J Pharm Pharmacol. 1974; 26:305. Rudy BC, Senkowski BZ. Analyt Profiles. 1973; 2:75. Benet LZ, Goyan JE. J Pharm Sci. 1965; 55:983. Pitman IH, et al. J Pharm Sci. 1968; 57:239. Taraszka MJ. J Pharm Sci. 1971; 60:946. Kaplan SA, et al. J Pharm Sci. 1974; 63:527. Timmermars PBMWM, van Zweiten PA. Arzn Forsch. 1978; 28:1676. Hurwitz AR, Liu ST. J Pharm Sci. 1977; 66:626. Hulshoff A, Perrin J. Pharm Acta Helv. 1975; 51:67. Barlow RB. Introduction to Chemical Pharmacology, ed. 2, p. 357. New York, Wiley, 1964. Chatten LG, Harris LE. Anal Chem. 1962; 34:1499.

65. 66. 67. 68. 69. 70. 71. 72. 73. 74. 75. 76. 77. 78. 79. 80. 81. 82. 83. 84. 85. 86. 87. 88. 89. 90. 91. 92. 93. 94. 95. 96. 97. 98. 99. 100. 101. 102. 103. 104. 105. 106. 107. 108. 109. 110. 111. 112. 113. 114. 115. 116. 117. 118. 119. 120. 121. 122. 123. 124. 125. 126. 127. 128. 129. 130.

Wang ESN, Hammerlund ER. J Pharm Sci. 1970; 59:1561. Vallner JJ, et al. J Pharm Sci. 1976; 65:873. Hengstmann JH, et al. Analyt Chem. 1974; 46:35. Jons WH, Bates TR. J Pharm Sci. 1970; 59:329. Langecker AA, et al. Arch Exp Pathol Pharmacol. 1954; 222:584. Truant AP, Takman B. Anesth Analg. 1959; 38:478. Cho MJ, et al. J Pharm Sci. 1971; 60:197. Bates RG. Ann NY Acad Sci. 1961; 92:341. Pothisiri P, Carstensen JT. J Pharm Sci. 1975; 64:1933. Terrada H, et al. J Med Chem. 1974; 17:330. Cohen JL. Analyt Profiles. 1978; 6:108. Peeters JJ. J Pharm Sci. 1978; 67:129. Sturgeon RJ, Schulman SG. J Pharm Sci. 1977; 66:959. Jaffe JM, et al. J Pharmacokin Biopharm. 1973; 1:281. Janicki CA, Gilpin RK. Analyt Profiles. 1978; 7:181. Marten RB. J Phys Chem. 1971; 75:2659. Maulding HV, Zoglio MA. J Pharm Sci. 1970; 59:700. Garrett ER, et al. J Pharm Sci., 1970; 59:1449. Mann JM. Analyt Profiles. 1972; 1:107. Shepherd RG, et al. Ann NY Acad Sci. 1966; 135:698. Butler TC. J Am Pharm A. 1955; 44:367. Ward CK, Schirmer RE. Analyt Profiles. 1977; 6:165. Waysek, EH, Johnson JH. Analyt Profiles. 1976; 5:128. Rudy BC, Senkowski BZ. Analyt Profiles. 1973; 2:234. Florey K. Analyt Profiles. 1973; 2:254. Rudy BC, Senkowski BZ. Analyt Profiles. 1974; 3:321. Buzard JA, et al. Am J Physiol. 1961; 201:492. McCallister JB, et al. J Pharm Sci. 1970; 59:1288. Perel JM, et al. Biochem Pharmacol. 1964; 13:1305. DeLuca PP, et al. J Pharm Sci. 1973; 62:1321. Janssen PAJ, et al. J Med Pharm Chem. 1959; 1:282. Satzinger G, et al. Analyt Profiles. 1978; 7:284. Parrott EL, Saski W. Exper Pharm Technol, p. 255, Minneapolis, Burgess, 1965. Paiva TB, et al. J Med Chem. 1970; 13:690. Naik, et al. Pharm Sci. 1976; 65:275. Garrett ER. J Pharm Sci. 1962; 51:445. Smith RB, et al. J Pharm Sci. 1976; 65:1209. Florey K. Analyt Profiles. 1978; 7:325. Upjohn product information 1975. Prusoff WH. Pharmacol Rev. 1967; 19:223. Fucella LM, et al. Clin Pharmacol Therap. 1975; 17:277. Neudent W, Rpke H. Chem Ber. 1954; 87:666. Rudy BC, Senkowski BZ. Analyt Profiles. 1973; 2:307. Brewer GA. Analyt Profiles. 1978; 6:198. Lewis GG. Brit J Pharmacol. 1954; 9:488. Cohen ML, Trevor AJ. J Pharmacol Exp Ther. 1974; 189:354. Rudy BC, Senkowski BZ. Analyt Profiles. 1973; 2:354. Kappe T, Armstrong MD. J Med Chem. 1965; 8:371. Gorten JE, Jameson RF. J Chem Soc. 1968; (A):2615. Narahashi TI, et al. J Pharmacol Exp Ther. 1970; 171:32. Hoerksema H. J Am Chem Soc. 1964; 86:4223. Smith RL. Med Chem. 1964; 2:477. Barrett J, et al. J Pharm Pharmacol. 1973; 25:389. Persson BA, Schill G. Acta Pharm Suec. 1966; 3:291. le Pettit GF. J Pharm Sci. 1976; 65:1095. Sandoz Pharmaceuticals brochure, 1962. Fox JJ, et al. J Amer Chem Soc. 1958; 80:1672. Zalipsky JJ, et al. J Pharm Sci. 1975; 65:461. Bush MT, et al. Clin Pharmacol Therap. 1966; 7:375. Liegler DG, et al. Clin Pharmacol Therap. 1969; 10:849. Raihle JA. Analyt Profiles. 1976; 5:320. Balasz L, Pungor E. Mikrochim Acta. 1962:309 through Chem Abstr. 1962; 56:13524g. Halmekowski J, Hannikainen H. Acta Pharma Suec. 1966; 3:145. Siegel S, et al. J Am Pharm A. 1959; 48:431. Glynn GL, Lamb DJ. J Pharm Sci. 1970; 59:1436. Rudy BC, Senkowski BZ. Analyt Profiles. 1973; 2:376.

131. 132. 133. 134. 135. 136. 137. 138. 139. 140. 141. 142. 143. 144. 145. 146. 147. 148. 149. 150. 151. 152. 153. 154. 155. 156. 157. 158. 159. 160. 161. 162. 163. 164. 165. 166. 167. 168. 169. 170. 171. 172. 173. 174. 7. 11. 15. 16. 23. 29. 30. 32. 33. 34. 35. 36. 37. 40. 41. 42. 50. 52. 53.

Schwartz DE, Jeunet F. Chemother. 1976; 22:19. Peetere J. J Pharm Sci. 197; 67:129. Dudzinski J, et al. J Pharm Sci. 1973; 62:624. Storoscik R, et al. Acta Pol Pharm. 1971; 28:601 through Chem Abstr. 1972; 76:158322k. Chowhan ZT. J Pharm Sci. 1978; 67:1258. Barlow RB, Hamilton JT. Brit J Pharmacol. 1962; 18:543. Sanders HJ et al. Ind & Eng Chem. 1955; 47:358. Shearer CM, Pilla CR. Analyt Profiles. 1974; 3:452. Frazakenly GV, Jackson EG. J Pharm Sci. 1968; 57:335. Elpern B. Ann NY Acad Sci. 1968; 148:579. Stella VJ, Pipkin JD. J Pharm Sci. 1976; 65:1160. Dayton PG, et al. Fed Proc. 1959; 18:382. Riegelman S, et al. J Pharm Sci. 1962; 51:129. Agarwal SP, Blake MI. J Pharm Sci. 1958; 57:1434. Bansal PC, Monkhouse PC. J Pharm Sci. 1977; 66:820. Christophers SR. Ann Trop Med. 1937; 31:43. Dox T, et al. Iyakirkin Kenkyn. 1978; 9:205 through Chem Abstr. 1978; 88:141601a. Poet RB, Kadin H. Analyt Profiles. 1975; 4:360. Strobel GB, Bianchi CP. J Pharmacol Exp Ther. 1970; 172:5. Rucki RJ. Analyt Profiles. 1976; 5:415. Cromble KB, Cullen LF. Analyt Profiles. 1973; 2:452. Garrett ER, Weber DJ. J Pharm Sci. 1970; 59:1389. Carlin HS, Perkins AJ. Am J Hosp Pharm. 1968; 25:271. Snell EE. Vitamins and Hormones. 1958; 16:84. Gallo AG, Radaelli P. Analyt Profiles. 1976; 5:483. Knochel JP, et al. J Lab Clin Med. 1965; 65:361. Garrett ER, Schnelle K. J Pharm Sci. 1971; 60:836. Conners KA. Textbook of Pharmaceutical Analysis, p. 475, New York, John Wiley & Sons, 1967. Suzuki A, et al. J Pharm Sci., 1970; 59:651. Brueckner AH. Yale J Biol Med. 1943; 15:813. Nygard B, et al. Acta Pharm Suec. 1966; 3:313. Post A, Warren RJ. Analyt Profiles. 1976; 5:241. Shore RA, et al. J Pharmacol Exp Ther. 1957; 119:361. Blessel KW, et al. Analyt Profiles. 1973; 2:564. Kaplan SA. J Pharm Sci. 1970; 59:358. De Angelis RL, et al. J Pharm Sci. 1977; 66:842. Blessel KW, et al. Analyt Profiles. 1974; 3:577. Papastephanou C. Analyt Profiles. 1978; 7:492. McLean WM, et al. J Pharm Sci. 1967; 56:1614. White A, et al. Principles of Biochemistry, p. 184, New York, McGraw-Hill, 1968. Neuss N, et al. J Am Chem Soc. 1959; 81:4754. Hiskey CF, et al. J Pharm Sci. 1962; 51:43. Hempelmann FW. Arzn Forsch. 1977; 27:2140. Burnes JJ. J Am Chem Soc. 1953; 75:2345. Barrett J, Smyth WF, Davidson IE. J Pharm Pharmaco. 1973; 25:38. Perrin DD. Dissociation constants of bases in aqueous solution. Butterworths, London, Supplement, 1972. Hoover JE (ed.). Dispensing of medication. Ed., Mack Publishing Co., Easton, PA, pp. 230, 247, 41:468-634, 1976. Ritschel WA. In Francke DE and W____H.A.K. Jr., Eds. perspectives in Clinical Pharmacy, Drug Intelligence Publications, Hamilton, IL, pp. 32- , 1972. Martin AN, Swarbrick J, Cammarata A. Physical Pharmacy, 2nd Ed., Lea & Febiger, Philadelphia, PA, pp 194, 309-313, 1969. Smith SE, Rawlins MD. Variability in Human Drug Response, Butterworths, London, pp. 154-165, 1973. Avery GS (Ed.): Drug Treatment, Publishing Sciences Group, Inc., Littleton, MA, pp. 890-896, 1976. Windholz M. (Ed.): The Merck Index, 9th Ed., Merck & Co., Rahway, NJ, 1976. Florey K. (Ed.): Analytical Profiles of Drug Substances, vol. 1, Academic Press, New York, NY, 1972. Ibid., Vol. 2, 1973. Ibid., Vol. 3, 1974. Ibid., Vol. 4, 1975. Ibid., Vol. 5, 1976 Maren TH, Mayer E, Wadsworth BC. Bull Johns Hopkins Hosp. 1954; 95:199-243. Skovsgaard T, Nissen NI. Dan Med Bull. 1975; 22:62-73. Anon. American Hospital Formulary Service, American Society of Hospital Pharmacists, Washington, DC, 1977. Chatten LG (Ed.): Pharmaceutical Chemistry, Vol. 1, Marcel Dekker, New York, NY, pp. 85-87, 1966. Hengstein JH, Falkner FC, Watson JT. Anal Chem. 1974; 46:34-39. Kaplan SA, Jack ML, Weinfeld RE, et al. J Pharmacokinet Biopharm. 1976; 4:1-16.

54. 56. 59. 60. 61. 69. 72. 73. 75. 81. 82. 84. 85. 88. 94. 115. 116. 117.

Lordi NG, Christian JE. J Am Pharm Assoc., 1956; 45:300-305. Spencer JL, Flynn EH, Roeske RW, et al. J Med Chem. 1966; 9:746-750. Barlow RB. Introduction to Chemical Pharmacology, 2nd Ed., John Wiley and Sons, New York, NY, p. 124, 357, 1964. Person Communication: Dr. R.L. Charles, Searle Laboratories, Chicago, IL, 1975. Green AL. J Pharm Pharmacol. 1967; 19:10-16. Maulding HV, Zoglio MA. J Pharm Sci. 1970; 59:700, 701. Leffler EB, Spencer HM, Burger A. J Am Chem Soc. 1951; 73:2611-2613. Clouet DH (Ed.): Narcotic Drugs Biochemical Pharmacology, Plenum Press, New York, NY, pp. 52, 53, 1971. Wiseman EH, McIlhenny HM, Bettis JW. J Pharm Sci., 1975; 64:1469-1475. Pardo A, Vivas S, Espana F, et al. Afinidad. 1972; 29:640-642. Persson B-A. Acta Pharm Suecica. 1968; 5:335-342. Salvesen B, Glendrange JH. Medd Norsk Farm Selsk. 1966; 28:272-278. Hoeksema H, Bannister B, Birkenmeyer RD, et al. J Am Chem Soc. 1964; 86:4223, 4224. Suzuki A, Higuchi WI, Ho NFH. J Pharm Sci. 1970; 59:652-659. Personal Communication: Dr. W. E. Scott, Hoffmann-LaRoche, Nutley, NJ 1975. Brimblecombe RW, Duncan WAM, Durant GJ, et al. J Int Med Res. 1975; 3:86-92. Roseman TJ, Yalkowsky SW. J Pharm Sci. 1973; 62:1680-1685. Anon: Norpace (Disopyramide Phosphate) Prescribing Information Brochure 7N17, Searle Laboratories, Chicago, IL, (Aug.) 1977.