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.
Andrisano
V
V
Dipartimento di Scienze Farmaceutiche, Università di Bologna, Via Belmeloro 6, 40126 Bologna, Italy.
Ballardini
R
R
Hrelia
P
P
Cameli
N
N
Tosti
A
A
Gotti
R
R
Cavrini
V
V
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