A brief review of pKa values and their uses in pharmacy practice is presented. Tables of pKa values for 400 medicinal compounds, of pH values of 18 body fluid sites, and of electron-inducing chemical substituents are provided. Adequate literature sources are included to permit further reference to the more detailed aspects of conditions associated with pKa value determinations or uses.
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References
1.
AlbertA.SerjeantE. P.: The Determination of Ionization Constants, Chapman and Hall Ltd., London, 1971.
2.
CooksonR. F.: The Determination of Acidity Constants, Chem. Rev.74: 5–27 (Jan.) 1974.
3.
ConnorsK. A.: A Textbook of Pharmaceutical Analysis, 2nd ed., John Wiley and Sons, New York, NY, pp. 127–133, 147, 184–186, 204, 205, 221, 222, 1975.
4.
BenetL. Z.GoyanJ. E.: Potentiometric Determination of Dissociation Constants, J. Pharm. Sci.56: 665–680 (June) 1967.
5.
ConnorsK. A.: In HiguchiT.Brochmann-HanssenE., eds., Pharmaceutical Analysis, John Wiley and Sons, New York, N.Y., pp. 226, 227, 1961.
6.
DaglishC.: In Isolation and Identification of Drugs, Vol. 1, The Pharmaceutical Press, London, pp. 97–100, 1969.
7.
BarrettJ.SmythW. F.DavidsonI. E.: An Examination of Acid-Base Equilibria of 1,4-Benzodiazepines by Spectrophotometry, J. Pharm. Pharmacol.25: 387–393, 1973.
8.
KrahlM. E.: The Effect of Variation in Ionic Strength and Temperature on the Apparent Dissociation Constants of Thirty Substituted Barbituric Acids, J. Phys. Chem.44: 449–463 (Apr.) 1940.
9.
HallN. F.SprinkleM. R.: Relations Between the Structure and Strength of Certain Organic Bases in Aqueous Solution, J. Am. Chem. Soc.54: 3469–3485 (Sept.) 1932.
10.
KolthoffI. M.BruckensteinS.: Acid-Bases in Analytical Chemistry, John Wiley and Sons, New York, N.Y.p. pp. 518–524, 1959.
11.
PerrinD. D.: Dissociation Constants of Organic Bases in Aqueous Solution, Butterworths, London, 1965; Supplement, 1972.
12.
KortiimG.VogelW.AndrussowK.: Dissociation Constants of Organic Acids in Aqueous Solution, Butterworths, London, 1961.
13.
NewtonD. W.: Potential Source of Error in Official Diazepam Assays, J. Pharm. Sci.67: 550–551 (Apr.) 1978.
14.
MarchJ.: Advanced Organic Chemistry: Reactions, Mechanisms, and Structure, McGraw-Hill, New York, N.Y. pp. 19–21, 1968.
15.
HooverJ. E., (ed.): Dispensing of Medication, 8th ed., Mack Publishing Co., Easton, PA, pp. 230, 247, 418–426, 468–634, 1976.
16.
RitschelW. A.: In FranckeD.E.WhitneyH. A. K.Jr., eds., Perspectives in Clinical Pharmacy, 1st Ed., Drug Intelligence Publications, Hamilton, IL, pp. 325–367, 1972.
17.
MilneM. D.: Influence of Acid-Base Balance on Efficacy and Toxicity of Drugs, Proc. Roy. Soc. Med.58: 961–963 (Apr. 9) 1965.
18.
DiechmanW. B.GerardeH. W.: Toxicology of Drugs and Chemicals, Academic Press, New York, N.Y., pp. 99, 121, 562, 1969.
LevyR. H.RowlandM.: Absorption Kinetics of a Series of Local Anesthetics from Rat Subcutaneous Tissue. I. J. Pharmacokinet. Biopharm.2: 313–335 (Aug.) 1974.
25.
RitchieJ. M.CohenP. J.: In GoodmanL. S.GilmanA., eds., The Pharmacological Basis of Therapeutics, Macmillan, New York, N.Y., pp. 383, 384, 1975.
26.
LeoA.HanschC.ElkinsD.: Partition Coefficients and Their Uses, Chem. Revs.71: 525–616 (Dec.) 1971.
27.
BellP. H.RoblinR. O.Jr.: Studies in Chemotherapy. VII. A Theory of the Relation of Structure to Activity of Sulfanilamide Type Compounds, J. Am. Chem. Soc.64: 2905–2917 (Dec.) 1942.
28.
NewtonD. W.McMullenJ. N.BeckerC. H.: Characteristics of Medicated and Unmedicated Microglobules Recovered from Complex Coacervates of Gelatin-Acacia, J. Pharm. Sci.66: 1327–1330 (Sept.) 1977.
29.
SmithS. E.RawlinsM. D.: Variability in Human Drug Response, Butterworths, London, pp. 154–165, 1973.
30.
AveryG. S., (ed.): Drug Treatment, Publishing Sciences Group Inc., Littleton, MA, pp. 890–896, 1976.
31.
WilsonC. O.GisvoldO.DoergeR. F.: Textbook of Organic Medicinal and Pharmaceutical Chemistry, 7th ed., J. B. Lippincott, Philadelphia, PA, pp. 973–977, 1977.
FloreyK., (ed.): Analytical Profiles of Drug Substances, Vol. 1, Academic Press, New York, N.Y.1972.
34.
Ibid., Vol. 2, 1973.
35.
Ibid., Vol. 3, 1974.
36.
Ibid., Vol. 4, 1975.
37.
Ibid., Vol. 5, 1976.
38.
AntonA. H.: A Drug-Induced Change in the Distribution and Renal Excretion of Sulfonamides, J. Pharmacol. Exp. Ther.134: 291–303 (Dec.) 1961.
39.
HiskeyC. F.CantwellF. F.: Ultraviolet Spectrum Correlations with the Conjugate Acid-Base Species of Acetarsone and Arsthinol, J. Pharm. Sci.57: 2105–2111 (Dec.) 1968.
40.
MarenT. H.MayerE.WadsworthB. C.: Carbonic Anhydrase Inhibition I. The Pharmacology of Diamox, 2-Acetylamino-1,3,4-thiadiazole-5-sulfonamide, Bull. Johns Hopkins Hosp.95: 199–243 (Nov.) 1954.
41.
SkovsgaardT.NissenN. I.: Adriamycin, An Antitumor Antibiotic: A Review with Special Reference to Daunomycin, Dan. Med. Bull.22: 62–73, 1975.
42.
Anon.: American Hospital Formulary Service, American Society of Hospital Pharmacists, Washington, D.C., 1977.
43.
BeckettA. H.: Analgesics and Their Antagonists: Some Steric and Chemical Considerations, J. Pharm. Pharmacol.8: 848–859 (Nov.) 1956.
44.
Personal Communication: Dr. C. F. Hiskey, Endo Laboratories, Garden City, N.Y. 1975.
45.
BakerB. R.JordaanJ. H.: Analogs of Tetrahydrofolic Acid XXVIII. Mode of Pyrimidine Binding to Dihydrofolic Reductase. pH Profile Studies, J. Pharm. Sci.54: 1740–1745 (Dec.) 1965.
46.
ShoreP. A.BrodieB. B.HogbenC. A. M.: The Gastric Secretion of Drugs: A pH Partition Hypothesis, J. Pharmacol. Exp. Ther.119: 361–369 (Mar.) 1957.
47.
RolinsonG. N.: Laboratory Evaluation of Amoxicillin, J. Infect. Dis.129: S139–S145 (June) 1974.
48.
WarrenR. J.BegoshP. P.ZaremboJ. E.: Identification of Amphetamines and Related Sympathomimetic Amines, J. Assoc. Off. Anal. Chem.54: 1179–1191 (Sept.) 1971.
49.
FincherJ. H.EntrekinD. N.HartmanC. W.: Surfactant-Base-Barbiturate Suppositories I. Rectal Absorption in Rabbits, J. Pharm. Sci.55: 23–28 (Jan.) 1966.
50.
ChattenL. G., (ed.): Pharmaceutical Chemistry, Vol. 1, Marcel Dekker, New York, N.Y. pp. 85–87, 1966.
51.
VreeT. B.MuskensA. T.RossumVanJ. M.: Some Physicochemical Properties of Amphetamine and Related Drugs, J. Pharm. Pharmacol.21: 774, 775 (Nov.) 1969.
52.
HengstenJ. H.FalknerF. C.WatsonJ. T.: Quantitative Determination of Guanethidine and Other Guanido-Containing Drugs in Biological Fluids by Gas Chromatography with Flame Ionization Detection and Multiple Ion Detection, Anal. Chem.46: 34–39 (Jan.) 1974.
53.
KaplanS. A.JackM. L.WeinfeldR. E.,: Biopharmaceutical and Clinical Pharmacokinetic Profile of Bromazepam, J. Pharmacokinet. Biopharm.4: 1–16 (Feb.) 1976.
54.
LordiN. G.ChristianJ. E.: Physical Properties and Pharmacological Activity: Antihistamines, J. Am. Pharm. Assoc. (Sci. Ed.)45: 300–305 (May) 1956.
55.
BorodkinS.YunkerM. H.: Interaction of Amine Drugs with a Polycarboxylic Acid Ion-Exchange Resin, J. Pharm. Sci.59: 481–486 (Apr.) 1970.
56.
SpencerJ. L.FlynnE. H.RoeskeR. W.: Chemistry of Cephalosporin Antibiotics. VII. Synthesis of Cephaloglycin and Some Homologs, J. Med. Chem.9: 746–750 (Sept.) 1966.
57.
FlynnE. H., (ed.): Cephalosporins and Penicillins, Academic Press, New York, N.Y. pp. 312–316, 1972.
58.
LinfordJ. H.: The Influence of pH on the Reactivity of Chlorambucil, Biochem. Pharmacol.12: 317–324 (Apr.) 1963.
59.
BarlowR. B.: Introduction to Chemical Pharmacology, 2nd ed., John Wiley and Sons, New York, N.Y., pp. 124, 357, 1964.
60.
Personal Communication: Dr. R. L. Charles, Searle Laboratories, Chicago, IL, 1975.
61.
GreenA. L.: Ionization Constants and Water Solubilities of Some Aminoalkylphenothiazine Tranquilizers and Related Compounds, J. Pharm. Pharmacol.19: 10–16 (Jan.) 1967.
62.
TaraszkaM. J.: Transfer of Clindamycin and 1′-Demethyl-4′-depropyl-4′-pentylclindamycin by the Cannulated-Everted Rat Gut, J. Pharm. Sci.60: 946–948 (June) 1971.
63.
KaplanS. A.AlexanderK.JackM. L.: Pharmacokinetic Profiles of Clonazepam in Dog, J. Pharm. Sci.63: 527–532 (Apr.) 1974.
64.
WangE. S. N.HammarlundE. R.: Corneal Absorption Reinforcement of Certain Mydriatrics, J. Pharm. Sci.59: 1559–1563 (Nov.) 1970.
65.
JohnsW. H.BatesT. R.: Quantification of the Binding Tendencies of Cholestyramine II: Mechanism of Interaction with Bile Salts and Fatty Acid Salt Anions, J. Pharm. Sci.59: 329–333 (Mar.) 1970.
66.
MartucciJ. D.SchulmanS. G.: The Fluorimetric Determination of Dibucaine, Anal. Chim. Acta77: 317–319 (July) 1975.
67.
HouJ. P.PooleJ. W.: The Amino Acid Nature of Ampicillin and Related Penicillins, J. Pharm. Sci.58: 1510–1515 (Dec.) 1969.
68.
ChoM. J.MitchellA. G.PernarowskiM.: Interaction of Bishydroxycoumarin with Human Serum Albumin, J. Pharm. Sci.60: 196–200 (Feb.) 1971.
69.
MauldingH. V.ZoglioM. A.: Physical Chemistry of Ergot Alkaloids and Derivatives I. Ionization Constants of Several Medicinally Active Bases, J. Pharm. Sci.59: 700, 701 (May) 1970.
70.
SturgeonR. J.SchulmanS. G.: Electronic Absorption Spectra and Protolytic Equilibria of Doxorubicin: Direct Spectrophotometric Determination of Microconstants, J. Pharm. Sci.66: 958–961 (July) 1977.
71.
JaffeJ. M.ColaizziJ. L.PoustR. I.: Effect of Altered Urinary pH on Tetracycline and Doxycycline Excretion in Humans, J. Pharmacokinet. Biopharm.1: 267–282 (Aug.) 1973.
72.
LefflerE. B.SpencerH. M.BurgerA.: Dissociation Constants of Adrenergic Amines, J. Am. Chem. Soc.73: 2611–2613 (June) 1951.
73.
ClouetD. H., (ed.): Narcotic Drugs Biochemical Pharmacology, Plenum Press, New York, N.Y., pp. 52, 53, 1971.
74.
MarshallP. B.: Some Chemical and Physical Properties Associated with Histamine Antagonism, Br. J. Pharmacol.10: 270–278 (Sept.) 1955.
75.
WisemanE. H.McIlhennyH. M.BettisJ. W.: Flumizole, a New Nonsteroidal Anti-Inflammatory Agent, J. Pharm. Sci.64: 1469–1475 (Sept.) 1975.
76.
HadjuV. P.HäusslerA.: Untersuchungen mit dem Salidiureticum 4-chlor-N-(2-Furylmethyl)5-Sulfamyl-An-thranilsaure, Arzneim. Forsch.14: 709, 710 (June) 1964.
77.
Personal Communication: Dr. J. T. Baldini, Schering Corp. Kenilworth, N. J. 1975.
78.
JanssenP. A. J.WesteringhC.JageneauA. H. M.: Chemistry and Pharmacology of CNS Depressants Related to 4-(4-Hydroxy-4-phenylpiperidino) butyrophenone. Part I. Synthesis and Screening Data in Mice, J. Med. Pharm. Chem.1: 281–297 (June) 1959.
79.
NaikD. V.DavisB. R.MinnetK. M.: Fluorescence of Hydralazine in Concentrated Sulfuric Acid, J. Pharm. Sci.65: 274–276 (Feb.) 1976.
80.
GarrettE. R.: Prediction of Stability in Pharmaceutical Preparations. X. (Alkaline Hydrolysis of Hydrocortisone Hemisuccinate), J. Pharm. Sci.51: 445–450 (May) 1962.
81.
PardoA.VivasS.EspanaF.: Studies on the Structure-Activity Relationship of Tricyclic Psychodrugs. III. Dissociation Constants, Afinidad29: 640–642 (July-Aug.) 1972.
82.
PerssonB-A.: Extraction of Amines as Complexes with Inorganic Anions, Acta Pharm. Suecica5: 335–342, 1968.
83.
DavisL. J.: Ibuprofen, Drug Intell. Clin. Pharm.9: 501–503 (Sept.) 1975.
84.
SalvesenB.GlendrangeJ. H.: The Potentiometric Determination of the Dissociation Constants of Isoniazid and Iproniazid, Medd. Norsk. Farm. Selsk.28: 272–278, 1966.
85.
HoeksemaH.BannisterB.BirkenmeyerR. D.: Chemical Studies on Lincomycin. I. The Structure of Lincomycin, J. Am. Chem. Soc.86: 4223, 4224 (Oct. 5) 1964.
86.
PerssonB-A.SchillG.: Extraction of Amines as Complexes with Inorganic Ions. Part 2, Acta Pharm. Suecica3: 281–302, 1966.
87.
SorbyD. L.PleinE. M.BenmamanD.: Adsorption of Phenothiazine Derivatives by Solid Adsorbents, J. Pharm. Sci.55: 785–794 (Aug.) 1966.
88.
SuzukiA.HiguchiW. I.HoN.F.H.: Theoretical Model Studies of Drug Absorption and Transport in the Gastrointestinal Tract II, J. Pharm. Sci.59: 651–659 (May) 1970.
89.
BrownD. J.MasonS. F.: Purine Studies. Part III. The Structure of the Monohydroxy- and Monomercaptopurines: Some Thiazolo [5:4-d] pyrimidines, J. Chem. Soc.1957: 682–689 (Feb.) 1957.
90.
LippoldB. C.JaegerI.: Stabilitat Sowie Dissoziationskonstanten von L-Dopa und α-L-Methyldopa, Arch. Pharmaz.306: 106–117 (Feb.) 1973.
91.
SiegelS.LachmanL.MalspeisL.: A Kinetic Study of the Hydrolysis of Methyl-DL-α-phenyl-2-piperidylacetate, J. Am. Pharm. Assoc. (Sci. Ed.)48: 431–439 (Aug.) 1959.
92.
FlynnG. L.LambD. J.: Factors Influencing Solvolysis of Corticosteroid-21-Phosphate Esters, J. Pharm. Sci.59: 1433–1438 (Oct.) 1970.
Personal Communication: Dr. W. E. Scott, Hoffmann-LaRoche, Nutley, N.J. 1975.
95.
ClarkeH. T.JohnsonJ. R.RobinsonR.: The Chemistry of Penicillin, Princeton University Press, Princeton, N.J. p. 419, 1949.
96.
RolloI. M.: Physicochemical Properties of Some Semisynthetic Penicillins, Can. J. Physiol. Pharmacol.50: 976–985 (Oct.) 1972.
97.
AgarwalS. P.BlakeM. I.: Determination of the pKa Value for 5, 5-Diphenylhydantoin, J. Pharm. Sci.57: 1434, 1435 (Aug.) 1968.
98.
BansalP. C.MonkhouseD. C.: Stability of Aqueous Solutions of Pirbuterol, J. Pharm. Sci.66: 819–823 (June) 1977.
99.
GarrettE. R.WeberD. J.: Metal Complexes of Thiouracils I. Stability Constants by Potentiometric Titration Studies and Structures of Complexes, J. Pharm. Sci.59: 1383–1398 (Oct.) 1970.
100.
CapomacchiaA. C.SchulmanS. G.: Electronic Absorption and Fluorescence Spectrophotometry of Quinacrine, Anal. Chim. Acta77: 79–85 (July) 1975.
101.
BatesT. R.LambertD. A.JohnsW. H.: Correlation Between the Rate of Dissolution and Absorption of Salicylamide from Tablet and Suspension Dosage Forms, J. Pharm. Sci.58: 1468–1470 (Dec.) 1969.
102.
GarrettE. R.SchnelleK.: Separation and Spectrofluorometric Assay of the β-Adrenergic Blocker Sotalol from Blood and Urine, J. Pharm. Sci.60: 833–839 (June) 1971.
103.
CarstensenJ. T.SerensenE. G.VanceJ. J.: Use of Hammett Graphs in Stability Programs, J. Pharm. Sci.53: 1547, 1548 (Dec.) 1964.
104.
BenetL. Z.GoyanJ. E.: Determination of the Stability Constants of Tetracycline Complexes, J. Pharm. Sci.54: 983–987 (July) 1965.
105.
CarlinH. S.PerkinsA. J.: Compatibilities of Parenteral Medications, Am. J. Hosp. Pharm.25: 270–279 (June) 1968.
106.
KaplanS. A.WeinfeldR. E.CotlerS.: Pharmacokinetic Profile of Trimethoprim in Dog and Man, J. Pharm. Sci.59: 358–363 (Mar.) 1970.
107.
DeAngelisR. L.KearneyM. F.WelchR. M.: Determination of Triprolidine in Human Plasma by Quantitative TLC, J. Pharm. Sci.66: 841–843 (June) 1977.
108.
DavsonH.GrahamL. T.Sr.: The Eye, Vol. 5, Academic Press, New York, N.Y. p. 121, 1974.