Determination of the enantiomers of bunolol in human urine by high-performance liquid chromatography on a chiral AGP stationary phase and identification of their metabolites by gas chromatography-mass spectrometry.

A high-performance liquid chromatographic method using a chiral AGP column was developed to screen and determine the enantiomers of bunolol in human urine. The recovery of (+)- and (-)-bunolol from urine was 91.79-95.23% at different concentrations. The coefficients of variation (C.V.) were less than 2.1 and 2.3% for intra- and inter-assays, respectively. Urinary metabolites were detected using GC-MS after derivatization with N-methyl(trimethylsilyl)trifluroacetamide. The influences of pH and modifier on a chiral AGP column were studied.

The disposition of bunolol in the rabbit eye.

Following topical administration to albino rabbits, bunolol hydrochloride, a beta 1- and beta 2-adrenoceptor antagonist, was rapidly absorbed and distributed in ocular tissues, and transformed intraocularly to a single metabolite, dihydrobunolol. The half-life of bunolol was approximately 1.26 hours in the aqueous humor and 1.63 hours in the ciliary body. There was no significant accumulation of bunolol during a four-day period of twice-daily dosing. Most of the drug was excreted in the urine following ocular or intravenous administration.

Bunolol metabolism by dogs: urinary excretion of 5-hydroxytetralone.

1. Anion exchange and t.l.c. were used to collect the polar drug metabolites present in urine of dogs treated orally with [14C]bunolol. 2. A new metabolite, 5-hydroxytetralone, was isolated, purified, and identified by u.v.,i.r. and mass spectroscopy. 3. 5-Hydroxytetralone represented 1.7% dose excreted in urine collected for 24 h after bunolol administration. 4. Properties of the metabolite are discussed in relation to the question of whether 5-hydroxytetralone was excreted as a conjugate.

l-bunolol metabolites in human urine.

Nine radiolabeled compounds were identified in human urine after administering a single oral dose of 3H-l-bunolol (3 mg) to 5 male volunteers. These compounds represented 54.7% of the dose and 71.4% of the isotope excreted in 3 days. Intact bunolol accounted for 14.7% of the dose and its conjugates totaled an additional 5.0%. The major drug metabolite (28.2% of dose) was dihydrobunolol, a reduction product known to have the same pharmacological activity and potency as bunolol. Dihydrobunolol conjugates amounted to 3.9% of the dose. Two minor acidic metabolites were produced by oxidative cleavage of the bunolol side chain, and another minor metabolite (hydroxydihydrobunolol) resulted from both reductive and oxidative biotransformation. Bunolol metabolism in man showed qualitative and quantitative differences from patterns observed in the rat and dog.

l-Bunolol metabolism in rats: identification of urinary metabolites.

Urine collected for 24 hr from rats given a single oral dose of 3H-l-bunolol (10 mg/kg) was found to contain only 25.8% of the dose and more than 30 labeled compounds. Nine compounds were identified and quantified as follows: bunolol (0.35% of urinary tritium), bunolol glucuronide (5.12%), bunolol sulfate (0.08%), dihydrobunolol (0.08%), dihydrobunolol glucuronide (0.74%), dihydrobunolol sulfate (0.12%), hydroxydihydrobunolol (0.58%), beta-(5-oxytetralonyl)lactic acid (0.74%), and (5-oxytetralonyl) acetic acid glucuronide (1.12%). The total quantity of identified labeled compounds was only 2.3% of the dose and 8.9% of the urinary radioactivity.

Bunolol metabolism by dogs: identification of basic metabolites and their conjugates.

Female beagles dosed once with encapsulated 14C-bunolol (10 mg/kg) excreted 61% of the isotope in urine in 24 hr. The pooled urine contained a minimum of 18 labeled compounds. Two previously unknown metabolites were purified and were identified by UV and mass spectral data; they were hydroxybunolol (10.1% of urinary radioactivity) and hydroxydihydrobunolol (9.8%). The urine also contained bunolol (0.7% of urinary carbon-14), dihydrobunolol (0.5%), conjugated dihydrobunolol (2.8%), beta-(5-oxytetralonyl)lactic acid (16.3%), and (5-oxytetralonyl) acetic acid (7.1%).