Studies on the photostability and in vitro phototoxicity of Labetalol.
The purpose of this study was to obtain information on the photochemical and phototoxic properties of Labetalol, a beta-blocker drug. Preliminary information on the drug photoreactivity was achieved using a flow system with a photochemical reactor on-line with a diode array detection system. Photophysical and photochemical investigations on the drug were performed in aqueous solutions at different pH values using spectrophotometric and fluorimetric methods; the photodegradation quantum yield was found to be 2.7 x 10(-3) at pH 5.8 and 1.5 x 10(-2) at pH 11.5. Forced photodegradation of labetalol solutions under exposure to UVA--UVB radiations (xenon arc lamp) was monitored by reversed-phase liquid chromatography. The main photodegradation products were isolated and characterized by NMR and mass spectrometry; labetalol was found to give 3-amino-1-phenylbutane and salicylamide-4-carboxaldehyde as the main photoproducts. Preliminary phototoxic testings on human keratinocyte cultures were performed evaluating the viability of the cells by the neutral-red uptake assay; mutagenic and photomutagenicity tests were also carried out based on Salmonella typhimurium strains. As a result, labetalol was found to be photolabile,mainly in alkaline medium, but evidences of significant phototoxic and photomutagenic effects by the drug were not observed.
Dipartimento di Scienze Farmaceutiche, Università di Bologna, Via Belmeloro 6, 40126 Bologna, Italy.
V
V
Andrisano
R
R
Ballardini
P
P
Hrelia
N
N
Cameli
A
A
Tosti
R
R
Gotti
V
V
Cavrini
D016475:3T3 Cells; D000319:Adrenergic beta-Antagonists / Q000737:chemistry / Q000494:pharmacology* / Q000528:radiation effects; D000818:Animals; D002478:Cells, Cultured; D006801:Humans; D015603:Keratinocytes / Q000187:drug effects* / Q000528:radiation effects; D007741:Labetalol / Q000737:chemistry / Q000494:pharmacology* / Q000528:radiation effects; D051379:Mice; D051381:Rats; D012486:Salmonella typhimurium / Q000187:drug effects* / Q000528:radiation effects; D014466:Ultraviolet Rays / Q000009:adverse effects
D000319:Adrenergic beta-Antagonists; D007741:Labetalol