Determination of naphazoline hydrochloride in biological and pharmaceutical samples by a quantum dot-assisted chemiluminescence system using response-surface methodology.

A simple and highly sensitive chemiluminescence (CL) method is reported for the determination of naphazoline hydrochloride (NH). It was found that the weak CL from the reaction of luminol and KIO4 in an alkaline medium could be highly amplified by cysteine-capped cadmium telluride quantum dots (QDs) and the enhanced CL was effectively quenched by NH and this finding was utilized as a basis for the determination of NH. The QDs were synthesized in aqueous medium and characterized by X-ray diffraction (XRD), transmission electron microscopy (TEM), and UV-vis and photoluminescence spectroscopy. A possible mechanism was proposed for the CL system based on radical identification experiments, along with CL spectrum of the system. The experimental parameters were optimized by the reliable response surface methodology (RSM). Under the optimized experimental conditions, the proposed method allowed the determination of NH over the range of 5.0 × 10(-10) -2.0 × 10(-7) mol/L (r(2) = 0.9993, n = 10). The precision (RSD%) of the method, obtained from five replicate determinations of 2.0 and 150 nmol/L NH, was found to be 1.0% and 1.3%, respectively. The method was successfully applied to the determination of NH in pharmaceutical formulations and human urine and serum samples with results corroborated with the aid of those obtained from a standard method.

[The study of naphthyzin present in material evidence and biological fluids].

The optimal conditions for isolation of naphazoline from naphthyzin preparations and biological fluids with chloroform at pH 9.18 are described. The compound of interest was identified with the use of color and precipitation reactions, IR and UV spectroscopy, thin-layer and gas chromatography, and chemical methods including high performance liquid chromatography, chromatodensitometry, and UV spectroscopy. The results obtained by the three methods are comparable.

Naphazoline intoxication in a child-a clinical and forensic toxicological case.

The imidazoline derivative naphazoline, an alpha(2)-adrenergic agonist, is used as non-prescription eye and nasal preparation because of its vasoconstrictive and decongestive properties. Especially in children, overdose and/or systemic side effects due to absorption can quickly cause severe central nervous system depression and cardiovascular adverse effects. In a 7-year-old boy was diagnosed a naphazoline intoxication by toxicological analysis. The case was also of forensic interest, because the naphazoline mixture was prepared in a pharmacy in a concentration 80 times above the adequate dosage for children. In general, physicians, pharmacists and the public should be educated about the toxicity of over-the-counter preparations.

The metabolism of nafimidone hydrochloride in the dog, primates and man.

1. The biotransformation of nafimidone, an imidazole-substituted anticonvulsant, has been studied by characterization of urinary metabolites in dogs, cynomolgus monkeys, baboons and man. 2. The biotransformation of nafimidone in these laboratory animals and man is initially very similar, in each case proceeding by reduction to the aliphatic alcohol metabolite, nafimidone alcohol or 1-[2-hydroxy-2-(2-naphthyl)ethyl]imidazole. 3. Further transformation of this metabolite involves oxidation in the naphthyl and imidazole functions, and/or conjugation. 4. The dog differs from the higher primates in that no metabolic modification of the naphthyl group takes place, the major metabolite in the dog being the O-beta-glucuronide of nafimidone alcohol. 5. In higher primates and man two isomers involving dihydroxylation in the naphthyl ring--1-[2-hydroxy-2-(5,6- or 7,8-dihydroxydihydro-2-naphthyl)ethyl]imidazole--were tentatively identified. These species alone showed evidence of an imidazole linked N-glucuronide of nafimidone alcohol. 6. The possible occurrence of stereoselective metabolism by the introduction of a chiral centre at C-9 in nafimidone alcohol was indicated in human urine by the presence of both epimers of the O-beta-glucuronide of nafimidone alcohol in a 2:1 ratio.

Pharmacokinetics of nafimidone in patients with chronic intractable epilepsy.

Nafimidone is a new antiepileptic drug which may be effective in partial onset seizures. We studied the pharmacokinetics of nafimidone and its metabolite, nafimidone alcohol, in 12 patients already taking phenytoin and/or carbamazepine. The half-life of nafimidone was 1.34 +/- 0.48 hours after a 100mg single dose and 1.69 +/- 0.91 hours after a 300mg single dose. However, the half-life of nafimidone alcohol increased from 2.84 +/- 0.72 hours after a 100mg single dose to 4.22 +/- 1.09 hours after a 300mg single dose (p less than 0.02). The clearance of nafimidone was 43.56 +/- 22.11 L/h/kg after a 100mg single dose and 35.51 +/- 28.93 L/h/kg after the 300mg single dose. The respective apparent volumes of distribution of nafimidone after single 100 and 300mg doses were 80.78 +/- 46.11 L/kg and 71.01 +/- 36.86 L/kg. After short term (9 to 10 weeks) and long term (127 to 152 weeks) maintenance therapy on nafimidone 600mg per day the half-life of nafimidone alcohol was 2.23 +/- 0.36 hours and 2.16 +/- 0.60 hours, respectively. No nafimidone could be detected in urine but from 4 to 7% of the daily nafimidone dose was recovered as nafimidone alcohol. Thus, it appears that over 90% of the administered dose of nafimidone is metabolised by pathways other than glucuronidation of nafimidone alcohol and urinary excretion.

High-performance liquid chromatographic determination of nafimidone and its major metabolite nafimidone alcohol in human plasma and urine.

A rapid, sensitive and selective method for the determination in plasma and urine of nafimidone, a new antiepileptic drug, and its major metabolite, nafimidone alcohol, has been developed which uses a high-performance liquid chromatographic system and a fluorescence detector for nafimidone or ultraviolet detector for nafimidone alcohol. The detection limits for nafimidone and nafimidone alcohol are 5.0 and 12.5 ng/ml, respectively.