Investigation of the photochemical properties and in vitro phototoxic potential of bumetanide

Abstract

The photophysical and photochemical properties of bumetanide, a sulfonamide diuretic drug, have been investigated and the photodegradation of the drug on exposure to UV-B and UV-A radiation monitored by fluorimetric and chromatographic (HPLC) methods. The main photoproducts were isolated by solid-phase extraction and liquid chromatographic procedures, and their structure elucidated by 1H-NMR and mass spectrometry. Bumetanide generates only extremely small quantities of singlet oxygen (1O2) upon irradiation in the presence of oxygen. The in vitro 3T3 N RU phototoxicity test yielded no evidence of phototoxic action.

Study on the photostability of guaiazulene by high‐performance liquid chromatography/mass spectrometry and gas chromatography/mass spectrometry

“…This method was chosen because RNO exhibits its absorption maximum at 440 nm with an absorption minimum over the range 310–370 nm, where GA absorbs. RNO bleaching, revealed by the decrease of the absorption at 440 nm, was obtained in the presence of the well‐known photosensitizer Rose Bengal16–18 and to a lesser extent with guaiazulene (Fig. 10).…”

“…To elucidate the mechanism of photodegradation and to obtain preliminary information on the phototoxicity, bleaching of RNO was used as an indicator for photoinduced generation of singlet oxygen (${}^{\rm 1}{\rm O}_{\rm 2}$ )13–15 in the presence of GA (as a photosensitizer) and histidine as a chemical trap for ${}^{\rm 1}{\rm O}_{\rm 2}$ . Rose Bengal was used as reference sensitizer 16–18. Briefly, the reaction solution contained 6.3 × 10 −6 M RNO, 5 × 10 −3 M histidine, and GA (2.3 × 10 −4 M) or Rose Bengal (5.4 × 10 −6 M) as sensitizer, in methanol.…”

CrossTalk proposal: Apical NKCC1 of choroid plexus epithelial cells works in the net inward flux mode under basal conditions, maintaining intracellular Cl− and cell volume

“…When bumetanide is excited at 340 nm, at pH 7.4, fluorescence emission peaks between 400 and 450 nm (Fiori et al . 2003), the emission wavelength at which Steffensen's group recorded the signals.…”

“…When excited at 340-345 nm, bumetanide fluorescence increases in a concentration-dependent manner, thereby overlapping with the SBFI excitation at 340 nm (Zhang et al 1993;Robertson & Foskett, 1995;Rose & Ransom, 1996). When bumetanide is excited at 340 nm, at pH 7.4, fluorescence emission peaks between 400 and 450 nm (Fiori et al 2003), the emission wavelength at which Steffensen's group recorded the signals.…”

Application of a physiologically‐based pharmacokinetic model for the prediction of bumetanide plasma and brain concentrations in the neonate

“…The mechanism underlying bumetanide's adjunct antiepileptic activity has been elucidated to be due to the inhibition of intracellular chloride accumulation through NKCC1, thereby facilitating the excitatory to inhibitory switch in gamma‐aminobutyric acid signalling (Ben‐Ari, ). However, the permeability of bumetanide across the blood–brain barrier (BBB) has been predicted and been shown experimentally to be a limiting factor, as it is a highly plasma protein bound, diprotic acid with pKa values of 3.6 and 7.7 (Fiori et al, ), therefore is > 99% ionized at physiological pH. Bumetanide has been shown to be a substrate of human organic anion transporter 3 (OAT3), murine organic anion‐transporting polypeptide 1a4 (Oatp1a4) and human multidrug resistance protein 4 (MRP4), which all operate as efflux transporters at the BBB at physiological pH (Donovan, O'Brien, Boylan, Cryan, & Griffin, ; Donovan, Schellekens, Boylan, Cryan, & Griffin, ; Puskarjov, Kahle, Ruusuvuori, & Kaila, ; Römermann et al, ).…”