Phytonadione Photostability

trans-2-NCA is proposed as a new simple and reproducible actinometer for calibrating the intensity of UV-A radiation from light sources in photostability testing of pharmaceuticals, since it exhibits some interesting properties which allow its use in ICH confirmatory studies. In particular: its absorption spectrum covers the full UV-A range, its photodegradation quantum yield over the UV-A range is dependent only on the photons number and not on the radiation wavelength, its photodegradation mechanism has been elucidated and the photodegradation rate is in the time of the photostability testing. Finally, the methanolic solution is stable for periodical preparations.

Studies are in progress on the characterisation of some full-spectrum lamps by a spectroradiometer, in order to express the effective UV-A integrated intensity (for example

□ 3:ester derivative

the 200 Whr/m2 recommended by ICH Photostability Guidelines for confirmatory studies)4 in terms of AA440 of the trans-2-NCA actinometer solutions exposed to these lamps.

References

2. H. H. T0nnesen, "Photostability of Drugs and Drug Formulations", H. H. Tonnesen, Ed., Taylor & Francis, London, 1996, Chapter 1, p. 1.

4. J. P. Riehl, C. L. Maupin and T. P. Layloff, Pharm. Forum, 1995, 21, 6, 1654.

6. J. T. Piechocki and R. J. Wolters, Pharm. Technol, 1993,17 (6), 46.

7. J. C. Scaiano, Ed., CRC Handbook of Organic Photochemistry, CRC Press, Boca Raton, FL, 1989, p. 188.

8. C. G. Hatchard and C. A. Parker, Proc. Royal Soc. London, 1956, A235, 518.

10. S. Yoshioka, Y. Ishihara, T. Terazono, N. Tsunakawa, T. Murai, T. Yasuda, Kitamura, Y. Kunihiro, K. Sakai, K. Hirose, K. Tonooka, K. Takayama, F. Imai, M. Godo, M. Matsuo, K. Nakamura, Y. Aso, S. Kojima, Y. Takeda and T. Terao, 1994, Drug Dev. Ind. Pharm., 20, 2049.

ll.S. Nema, R. J. Washkuhn and D. R. Beussink, Pharm. Technol., 1995,19, 172.

12. J. N. Pitts Jr, J. K. S. Wan and E. A. Schuck, J. Am. Chem. Soc., 1964, 86, 296.

13. P. M. Goman, Sirdesai, Sunil (Xytronyx, Inc.), "Aqueous printable phototranschromic inks for manufacture of UV dosimeters", PCT Int. Appl., WO 94 01, 20 Jan 1994, 503; Chem. Abstr., 1994,122: 163745y.

14. E. Fischer, EPA Newsletter, July 1984, 21, 33.

15. H. H. T0nnesen and J. Karlsen, Pharmeuropa, 1995, 7, 137.

Subject Index

AATCC (Am.Ass.Text.Chem.Col.), standards, 258 AATCC 16C-91 standard, 258 Aberchrome 540 actinometer, 302 Absorption spectrum, 249 Acetazolamide, 101

phototoxicity of, 113 Acrylamide polymerisation, test for radicals, 89, 138 Actinochrome 1R actinometer, 300 Actinochrome 2R actinometer, 302 Actinochrome N actinometer, 301 Actinometers, chemical, 68 quinine, 72, 228 well established, 299 Actinometry, 295 Action spectrum, 76 Activation spectrum, 249 Active ingredients of sunscreens, 171, 174 Adrenaline, 23 Adrenergics, 23

Adriamicyn, photoprotection of, 54 Albumin, photosensitisation test, 213 Alkenes, photochemistry of, 2 Allergy, photoinduced, 77, 78 Amberset, containers, 53 /rara-Aminobenzoic acid (PABA), 29 as protective agent, 132 in sunscreens, 171 as UV absorber, 54 Amiloride, 111 Aminopyrine, 9 5-Aminosalicylic acid, 7 Amiodarone, 20

Amodiaquine, 36 Amphotericin B, 52, 120 Anaesthetic drugs, 16 Analgesic drugs, 8, 9 Androstandione, 27 Androstendione, 27

ANSI (Am.Natl.Std.Inst.), lamp standards, 251

ANSLTESNA RP-27-1, 27-3, lamp standards, 254 Antiamebic drugs, 39 Antianginal drugs, 20

as photosensitisers, 196 Antiarrhythmic drugs, 20 as photosensitisers, 196 Antibacterials, 30

as photosensitisers, 196 Antibiotics, 32 Anticoagulant agents, 26 Anticonvulsant drugs, 16, 20 Antidepressants, as photosensitisers, 196 Antihepatitis drugs, 32 Antihistaminic drugs, 10 Antihyperlipoproteinemic drugs, 24 Antihypertensive drugs, 22

as photosensitisers, 196 Antiinflammatory drugs, as photosensitisers, 196, 203 non steroidal, 5, 150, 194 steroidal, 11 Antilipemics, as photosensitisers, 196 Antimalarial drugs, 36, 88 Antimycotics, 117 as photosensitisers, 196 topical forms, 130

Antineoplastic drugs, 39 Antioxidant activity, of Cu (II), 207 Antioxidants, 166, 199 Antiprotozoal drugs, 36 Antipsoriatic drugs, 29, 182 Antipsychotic drugs, 17, 134 Antipyretic drugs, 9 Antiseptics, 33 Antithrombotic agents, 24 Antitubercular drugs, 34 Antitumor drugs, 39 Antivirals, 30 Apazone, 10

Artificial illumination, 243 2-Arylpropionic acids, 5, 150

phototoxicity, 77, 79 Ascorbic acid phototoxicity reduction by, 113 as stabiliser, 132 ASTM (Am.Soc.Testing Mater.) standard, 227

ASTM G24 standard, 258 ASTM G3.03 standard, 254 Azapropazone, see Apazone Azathioprine, 10 Azobenzene (Actinochrome 2R)

actinometer, 302 Aztreonam, 32

Barbital, 14

Barbituric acid derivatives, 14 Beer-Lambert law, 82 Bemetizide, phototoxicity of, 114 Bendroflumethazide, phototoxicity of 113

Benorylate, 7 Benoxaprofen, 5 Benzodiazepines, 16 Benzophenone-3, 172 Benzophenone-8, 172 Benzydamine hydrochloride, 7 Bethametasone, 12 Bezafibrate, 24 Bifonazole, 120 Bilirubin, 79

Black-light lamps, blue, 229

BL-0 and BL-N, 250 Bleomycins, 40

Blood pressure regulating drugs, 21 Bumetanide, phototoxicity of, 113 Butifen, 5

Butizide, phototoxicity of, 114 Calciferol, 43

Capsules, photostability of, 230 Carbamazepine, 20, 51 Carbonyl, photocleavage of, 2 photoreactivity of, 2 Cardiac agents, 20 Cardiotonic drugs, 20 Carmustine, 39

p-Carotene, radical scavenger, 113 Catechin, 32 Cathecolamines, 52 Cefotaxime, 32

Central nervous system, active drugs, 14 Cephaeline, photoprotection of, 54 Chamber for photostability testing, 272

validation of, 280 Chemotherapeutic agents, 30 Chloramphenicol, 31, 211 Chlordiazepoxide, 17 Chloride, aromatic, dechlorination, 2 Chloroquine, 36, 92 oxygen sensitisation by, 93 photohaemolysis by, 93 phototoxicity of, 94 solid state photochemistry, 94 Chlorothiazide, 101

phototoxicity of, 113 Chlorphenesin, 123 Chlorpromazine, 18, 212

phototoxicity of, 78 Chlorprothixene, 17 Chlortetracycline, 30 Chlorthalidone, phototoxicity of, 114 Cholesterol, photo-oxidation test, 213 C1E (Com.Int.Eclar.), lamp standards, 251

CLE 20, sun radiation definition, 284 CIE D65/ID65, lamp standard, 254, 280 Ciprofloxacin, 35 cw-Cyclooctene actinometer, 300 Cisplatin, 39 Clofibrate, 24

photoprotection of, 54 Clofibric acid, 24 Clomiphene, 28 Clopenthixol, 17 Clotrimazole, 117 Cloxiquine, 123

Cobalt (II), quencher of triplets, 93 Colchicine, photoprotection of, 54 Colorants, for photoprotection, 54 Colour index of lamps, 254 Coloured film for photoprotection, 53 Commercially available forms, photostability, 52 Cool While lamps, 229, 252, 266 Cortisone, 11 Coumarin, 162

excited states, 166 Cross-sensitisation (hydrochlorothiazide-

triamterene), 113 Cyanidol, 32

Cycloaddition, of cinnamates, 172, 190 Cyclobarbital, 15 (3-Cyclodextrin, complexation, 203 inclusion complexes, 151 for photoprotection, 54, 195 Cynnamic acid, 49

D65/ID65 standard, 68 Dacarbazine, 40

photoprotection of, 54 Daunorubicin, 40

photoprotection of, 54 Daylight, artificial, 260

fluorescent lamps, 252, 266 natural, 243, 260 N-Dealkylation, 10

Decarboxylation, of arylpropionc acids, 150, 203

Dehalogenation, of 2-chorophenothiazine, 138

of frusemide, 102 of hydrochlorothiazide, 109 7-Dehydrocholesterol, 77, 79 A9(11)-Dehydroestrone, 26 Demeclocycline, 31

photoprotection of, 54 N-Demethylation, of phenothiazines, 138 Dermatologicals, 28 Detector, spectral sensitivity, 254 Dexamethasone, 12 Diazepam, 16 Diclofenac, 7 Dienoestrol, 28

Diflunisal, photoprotection of, 207 Digitoxin, 20

9,10-Dihydroergotamine, 23 Dilthiazem, 22

Dimerization, of cinnamates, 186 2,5-Dimethylfuran, test for singlet oxygen, 89

DIN (German Inst.Std.), 258 DIN 53 387 standard, 258 Diphenylhydramine, 10 Dipyridamole, 26 Dithranol, 29 Diuretic drugs, 23, 100

as photosensitisers, 196 DNA, photo-cleavage of, 201 photo-damage of, 201 Dothiepin, 19 Doxepin, 19 Doxorubicin, 40

photoprotection of, 54 Drug preparation, photostability, 52 Drug products, photostability testing ,71, 230

sample analysis, 71 sample presentation, 71

Drug substance, photostability testing, 69, 230

sample analysis, 70 sample presentation, 69 Dyes, for photoprotection, 53, 54 for phototherapy, 78

Econazole, 120 Einstein, 82

Electron transfer, 155, 202 Electronic spectra, 75 Emetine, 39

photoprotection of, 54 Energy transfer, 75 Enoxacin, 203 Ephedrine, 23 EPR, 89 Ergotamine, 23 Erythema effectiveness, 290 Estrogens, 26 Estrone, 26 Ethacrynic acid, 101 Ethanol actinometer, 300 Ethinylestradiol, 26 Ethisterone, 27 Excited states, characterisation of, 90 lifetime of, 75, 90 Exposure dose, 290

FDA (US Food Drug Adm.), 227 Fenofibrate, 24 Filters, 254

solarization, 257 Flash photolysis, 90, 155, 212 Fluconazole, 120 Flucytosine, 117 Fluence, 290 Flunitrazepam, 17 Fluorescence, 90 Fluorescent tubes, 229 Fluoroquinolone antibiotics, 35, 194 as photosensitisers, 196 phototoxicity of, 79

Flupenthixol, 17 Fluphenazine, 134 Flurbiprofen, 5

Free radicals, 89, 150, 165, 171, 194 Fries, rearrangement photochemical, 7 Frusemide, 51, 102, 229 formulation stability, 107 free radicals production, 104 oxygen sensitisation by, 104 phototoxicity of, 113 triplet, 106 Furazolidone, 34 Furnidipine, 22

Furocoumarins, as photoallergens, 78 Furosemide, see Frusemide

Gemfibrozil, 24 Glass, absorption of, 53 Global solar irradiation, CEE definition, 275

Glucocorticosteroids, 11 photoprotection of, 54 Glutathione (GSH), 17

as photoprotective agent, 54, 77 Griseofulvin, 117

Haber-Weiss cycle, 197 Halomethasone, 14 Hammet plot, 137

Hatchard-Parker actinometer, 300, 305 Heating, during photostability testing, 285 Hedamycin, 40 Hexachlorophene, 32 Histidine, photodegradation test, 213 Hydrochlorothiazide, 108 free radicals production by, 110 oxygen sensitisation by, 110 photoprotection of, 54 phototoxicity of, 113 Hydrocortisone, 11

teri-butyl acetate, 11 Hydroflumethazide, phototoxicity of, 114 Hydrogen abstraction, by arylpropionic acids, 203

Hydrolysis, photochemical, of amiloride, 111 of frusemide, 107 of hydrochlorothiazide, 109 of pentobarbital, 107 Hydroxy radicals, 202 Hydroxychloroquine, 36 Hydroxylation, of phenothiazines, 138 Hypnotic drugs, 14 Histamine release, 197 Histidine oxidation, test for singlet oxygen, 89, 112

Ibuprofen, 5, 197 ICH Guideline, 291 content of, 243 lamp options, 257, 275 protocol, 239 ID65 standard, 68

EESNA (Hl.Eng.Soc.North Am.), lamp safety, 251 Immunosuppressant drugs, 10

as photosensitisers, 196 Inclusion complexes, with (3-

cyclodextrins, 151 Indapamide, 110 Indomethacin, 7, 197 Infrared radiation, in lamps, 262 Injections, photostability, 230 Inner filter effect, 83

in photoprotection, 54 Iodometry, for peroxide determination, 200

Iron oxides, for photoprotection, 54 Irradiance, 289

ISO (Int.Std.Org.), lamp standards, 258

ISO 105-B01 standard, 258

ISO 10977 standard, 68, 254, 275, 284

ISO 11341 standard, 277

ISO 11507 standard, 277

ISO 4892-2 standard, 254, 275

ISO 877 standard, 258

ISO 9379 standard, 284

ISO/DIS 105 standard, 277

Isoconazole, 120

trans-cis Isomerisation, of cinnamates, 172

Isoprenaline, 23 Isotretinoin, 211

JIS L 0841 (Jpn. Ind. Std.) standard, 258 JPMA ( Jpn.Pharm.Man.Ass.), phototest, 227

Ketoconazole, 121 Ketoprofen, 5, 150

photoprotection of, 207 Ketorolac tromethamine, 5 Kidamycin, 40

Kinetics of photochemical reactions, 297

Kolbe, reaction, photochemical, 5

Lamps, cool white fluorescent, 68 daylight, 68 infrared radiation, 262 lifetime of, 283 for photostability testing, 247 standards, 68, 85, 251 standardisation of, 266 near-ultraviolet, 68 Laser, Nd-YAG, 110 Leukotriene B4 antagonist, 182 Levonorgestrel, 27 Lifetime, of light sources, 283 Light, definition of, 252 intensity of, 84 sources, 68

spectral distribution of, 84 stressing, in the solid state, 184 in solution, 184 Lipid peroxidation, 150, 200 Lisozyme, photosensitisation test, 213 Lomefloxacin, 35 Luminance, 289

Lux, unsuitability of this unit, 254

Lynestrenol, 27

Malachite green actinometer, 300 Meclofenamic acid, 7 Medicinal photochemistry, 74 Mefloquine, 36, 96 oxygen sensitisation by, 96 phototoxicity of, 96 solid state photochemistry of, 96 Megestrol acetate, 229 Melanin, role in phototoxicity, 90 Menadiol, 44 Menadione, 44

photoprotection of, 54 Menaquinone-1,44 Menthyl anthranilate, 172 Mephobarbital, 14 6-Mercaptopurine, 40 Mestranol, 27

Metal complexation, for photoprotection, 195

Metal halide lamps, 254, 265 Methadone hydrochloride, 8 Methotrexate, 40 Methoxsalen, 29, 78 8-Methoxypsoralen, see Methoxsalen Methylene blue, 54 Metronidazole, 33, 229 photoprotection of, 54 Metyrapone, 50 Mexoryl, 174 Miconazole, 117

Micro-wave discharge lamps, 253 Midazolam, 16 Minimun exposure levels, 228 Minoxidil, 22 Mitonaftide, 39 Molsidomine, 22

photoprotection of, 54 Mutation, photoinduced, 77

Naftifine, 120 Nalidixic acid, 35 Naproxen, 5 photoprotection of, 207

Natamycin, 121 Nd-YAG laser, 110 Neuroleptics, 134 Niacinamide, 45 Nicardipine, 22

photoprotection of, 54 Nicotinic acid, 45 Nifedipine, 21, 132,211,229

photoprotection of, 54 Nimodipine, 22 Nitrazepam, 16 Nitrendipine, 22

Nitro group, aromatic, photoreactions, 2 Nitrofurantoin, 33

phototoxicity of, 77 Nitrofurazone, 34 fran.s-2-Nitrocynnamaldehyde actinometer, 306 photodegradation of, 313 stability of, 312 temperature effect on, 311 Norethisterone, 26, 27 Norrish Type I fragmentation, 2, 50 Norrish Type It fragmentation, 2 NSAIDS, see Antiinflammatory drugs, non steroidal Nystatin, 121

Octocrylene, 172 Octylmethoxycinnamate, 172 Octylsalicylate, 172 Ofloxacin, 35 Opacisers, 53 Opaque containers, 53 Oxiconazole, 120

N-Oxidation, of phenothiazines, 138 TV-Oxides, photochemistry of, 2 phototoxicity of, 81 Oxolinic acid, 35 Oxygen, reactive species (ROS) 90 singlet, see Singlet oxygen

Package, 53

Padimate-O, 172

Parentheral solution, photostability of, 52

Parsol-1789, 172

Penems, 32

Pentobarbital, 15

Perphenazine, 134

Pharmaceutical form, photostability of, 54 Phenothiazine drugs, 17, 134 kinetics of, 138

solid state photochemistry of, 146 Phenylbutazone, 9 Phenylpropionic acids, see 2-

Arylpropionic acids Phenyltoin, 20 Phosphor lamps, 252, 266 Phosphorescence, 90 Photoallergy, 197 Photochemical kinetics, 83 Photochemistry, of antimalarials, 87 of antimycotics, 116 of coumarin, 162 of diuretic drugs, 100 of drugs, 1 containing a benzophenone-like chromophore, 150 comparison with photosensitisation, 211

of Leukotriene B4 antagonists, 187 medicinal, 74 of phenothiazines, 134 of sunscreens active ingredients, 171 Photochromic actinometers, 302 Photodiodes, 295 Photodynamic reactions, 76, 224 Photohaemolysis, 150, 199 by antimalarials, 90 by diuretic drugs, 113 Photoionisation, of 2-arylpropionic acids, 156 of amiloride, 111 of triamterene, 113 Photolysis, apparatus for, 229 Photometabolites, 77 Photomultipliers, 295

Photoprotection, 195 by Co(II), Cu(II), Mn(II), 205 by cyclodextrins, 207 by metal complexation, 205 by polymer incorporation, 207 Photoreactions, for analysis, 52 oxygen effect on, 51 rate of, 83, 85 in the solid state, 49, 187 Type I, 76 Type H, 76 Type m, 76 wavelength effect, 51 Photoreactivity, medium effect on, 88 quantitative assessment of, 85 Photosensitisation, 194, 211 Photosensitisers, 76, 195 Photostability, assessment of, 52 ICH Guideline, 66 testing, 66, 227, 243, 247 confirmatory studies, 69 dark control, 68, 285 decision flow chart, 67 for drug products, 71, 230 for drug substances, 69, 230 exposure levels, 68, 69 forced degradation, 69 glossary, 73

heating, avoiding it, 285 judgement of results, 70, 72 presentation of samples, 69, 71 procedure, 68, 258 for registration application, 66 selection of batches, 66 surface temperature, 285 systematic approach, 66 Phototherapeutic drugs, 76 Phototherapy (PUVA), 77 Phototoxic drugs, 76 Phototoxicity, 197 dose dependence, 91 of diuretic drugs in cell cultures, 113

Phototoxicity, continued relation with structure, 79 systemic, 78

in vitro and in vivo studies, 80 Phototoxicology, 288 PhRMA (US Pharm.Res.Man.Ass.), 227 Phytonadione, for photoprotection, 54 Piretamide, phototoxicity of, 114 Polyaspartamides, for photoprotection, 207

ex,ß-Polyasparthydrazide (PAHy), 207 a,ß-Poly-(N-hydroxyethyl)-D,L-

aspartamide (PHEA), 207 Polymer incorporation, for photoprotection, 195 Polymerisation, 190

Polymorphism, effect on photochemistry, 190

Polythiazide, phototoxicity of, 114 Potassium ferrioxalate, actinometer, 300, 305

Potassium reinekate, actinometer, 301 Prednicarbate, 14 Prednisolone, 12 Prednisone, 12 Primaquine, 36, 94 oxygen sensitisation by, 95 photohaemolysis by, 96 phototoxicity of, 95 solid state photochemistry of, 96 Prochlorperazine, 134 Progesterone, 27 Progestinics, 26 Promethazine, 10

Protection, of photolabile drugs, 53 Protein cross-linking, 201 Protriptyline, 19 Proxibarbital, 14 Psoralens, 29, 77, 248 Psychotherapeutic agents, 17 Psychotropic agents, 19 Pyrazolones, 9 Pyridoxal 5-phosphate, 46 Pyridoxine, 45

Pyrithione, 34

Quantum yield, 81, 173, 178, 295

measurement, 298 Quenchers, 76

of singlet oxygen, 202 Quinine, 36 as actinometer, 72, 229, 306

Radiant exposure, 289 Radiation measuring devices, 285 Radiation system, 274 Radiometer, 68, 284 sensitivity of, 254 wavelength-dependent, 290 wavelength-independent, 290 Ranitidine, 52 Reference spectrum, 275 Reserpine, 22 Retinoic acid, 41

13-cis-, 211 Retinol, 41 Riboflavin, 45 Room light, 253, 266 window glass filtered, 259

Secobarbital, 15 Sedative drugs, 17 Serum lipid reducing agents, 24 Singlet oxygen, 2, 26, 29, 44, 51, 89, 150, 172, 194, 202 formation quantum yield, 212 quenchers of, 202 toxicity of, 77 Sodium azide, quencher of singlet oxygen, 202

Sodium bisulfite, stabiliser, 132 Sodium nitroprusside, 22

in infusion, 52 Sodium urate, for photoprotection, 54 Solar simulators, 85, 172 vs ICH Guideline, 293 room size, 288 Solar spectral irradiance, 259 Solar spectrum, 288

Solarization of filters, 257 Solid state, photodimerization, 184 photoreactions, 49, 91 topochemical control, 50 Solvated electrons, 194 Sources, 299 for photostability testing, 247 standardisation of, 266 Spectral functions, 275 Spectral power distribution (SPD), 247 Stability of drugs, ICH Guideline, 66 Steroids, gonadotropic, 26 Stilboestrol, 28 Sulbentine, 121 Sulfa drugs, 30 Sulfacetamide, 30 Sulfadimetoxine, 30 Sulfamethoxazole, 30 Sulfanylamide, 30 Sulfathiazole, photoprotection of, 54 Sulfoxidation, of phenothiazines, 138 Sun radiation, 284 Sunlight, natural, 172 simulated, 172, 290 Sunscreens, 29, 171 Suntest CPS, 121

Supercoiled plasmid linearization, 202 Superoxide anion, 51, 202 Superoxide dismutase (SOD), 89 Superoxide dismutase-like activity, of

Cu (ID, 207 Suprofen, 5, 150 photoprotection of, 207

Tablets, photostability of, 230 Tamoxifen, 28 Tauromustine, 39 TC02-2 standard lamps, 85 Temperature, effect on photoreactions, 154 measuring devices, 285 Terbutaline sulfate, 52 Terconazole, 120, 121 Terfenadine, 10

Testing chambers, 272 Testosterone, 27 17-methyl-, 27 propionate, 27 Tetrachlorosalicylanilide, 32 Tetracycline, 30 photoprotection of, 54 phototoxicity, 77 Thermopiles, 295 Thiamine, 45

Thiobarbituric acid, for peroxide determination, 200 2-Thiophenobarbital, 15 Thiorfan, 9 Thioridazine, 19 Thiotixene, 17 Thioxanthine drugs, 17 Thymine, 49 Thyroxine, 24 Tiaprofenic acid, 5, 150 Tioconazole, 121 Titanium dioxide, 171

as opaciser, 53 Tocopherol, a-Tocopherol, 43 photoprotection of, 54 phototoxicity reduction by, 113 Tolnaftate, 120 Topical bacteriostatics, as photosensitisers, 196 Topochemical control, 50 Tranquillisers, 14

as photosensitisers, 196 Triamcinolone, 12 Triamterene, 112 Trichlormethiazide, 24 phototoxicity of, 113 Tricyclic antidepressants, 19 Trifluoperazine, 134 Trimethoprim, 35 Triplet state, sensitisation, 219

2-arylpropionic acids, 155 Tryptophan ethyl ester, 213 L-Tryptophan, test for superoxide, 89 Tungsten halide lamps, 253, 266

Type I photochemistry, 76, 137, 168, 197 Type II photochemistry, 76, 137, 198 Type DI photochemistry, 76

Ubidecarenone, 20

photoprotection of, 54 Ubiquinone, radical scavenger, 113 Units of measure, of light exposure, 291 Uranyl oxalate actinometer, 300 Uric acid, for photoprotection, 54 Urocanic acid, for photoprotection, 54 UV adsorbers, 53, 54, 171 UV lamps hazard, 251 UV-A, fluorescent sources, 228 lamps, BL-0 and BL-N, 249 radiation, 171 UV-B radiation, 171

Valerophenone actinometer, 174 Validation, of photostability testing, 280 Vanillin, as protective agent, 132 as UV adsorber, 54

Vasoconstrictors, 23 Vasodilators, 21 Vinblastine sulfate, 39 Vita-Lite fluorescent sources, 241 Vitamins, 41

photoprotection of, 54 PP, 45

Warfarin sodium, 26

Wavelength effect, on photoreactions, 51

Xenobiotics, 194 Xenon arc vj ICH Guideline, 292 long arc sources, 254, 265 short arc sources, 265 Xipamide, phototoxicity of, 114

Zinc oxide, protective agent, 132 Zinostatin, 40

Since Pasteur in 1846, scientists have been aware that many drugs are photoreactlve, but until recently research in this area has been somewhat limited. However, since the introduction of acutely sensitive analytical methods, the realization of the need to identify the photochemical properties of a potential drug as early in Its development as possible and the increased attention to the phototoxic effects of drugs, more details are becoming available.

Drugs: Photochemistry and Photostability presents the basic elements of the science, and serves as an excellent introduction to this emerging field of photochemistry. Detailed experimental conditions for photostability studies are given, along with a discussion of the recently implemented ICH Guidelines for drug photostability.

With contributions from international experts in the field, and including a comprehensive literature review, this book provides all the up-to-date information needed by researchers in many fields, especially medicinal and pharmaceutical chemistry.

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