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Use of S-pentafluorophenyl tris(2,4,6-trimethoxyphenyl)phosphonium acetate bromide and (4-hydrazino-4-oxobutyl) [tris(2,4,6-trimethoxyphenyl)phosphonium bromide for the derivatization of alcohols, aldehydes and ketones for detection by liquid chromatography/electrospray mass spectrometry.

The synthesis of S-pentafluorophenyl tris(2,4,6-trimethoxyphenyl)phosphonium acetate bromide (TMPP-AcPFP) and the novel compound (4-hydrazino-4-oxobutyl) [tris(2,4,6-trimethoxyphenyl)phosphonium bromide (TMPP-PrG) is described and the use of these compounds as derivatizing reagents for alcohols, aldehydes and ketones evaluated. Methods have been developed for the pre-column derivatization of alcohols using TMPP-AcPFP and for aldehydes and ketones using TMPP-PrG. The reactions were investigated by the use of a variety of individual test compounds containing the target functional groups. The TMPP acetyl ester and TMPP propyl hydrazone derivatives formed with their respective target analytes produced an enhanced response in electrospray ionization mass spectrometry (ESI-MS), and reproducible chromatography. The use of these two reagents to derivatize and facilitate detection of alcohols (including sugars and steroids), aldehydes and ketones (including steroids) by LC/ESI-MS was investigated.

Alcohols↗

Pharmacokinetics and toxicity of bromide following high-dose oral potassium bromide administration in healthy Beagles.

The pharmacokinetics of a multidose regimen of potassium bromide (KBr) administration in normal dogs was examined. KBr was administered at 30 mg/kg p.o. q 12 h for a period of 115 days. Serum, urine, and cerebrospinal fluid (CSF) bromide (BR) concentrations were measured at the onset of dosing, during the accumulation phase, at steady-state, and after a subsequent dose adjustment. Median elimination half-life and steady-state serum concentration were 15.2 days and 245 mg/dL, respectively. Apparent total body clearance was 16.4 mL/day/kg and volume of distribution was 0.40 L/kg. The CSF:serum BR ratio at steady-state was 0.77. Dogs showed no neurologic deficits during maintenance dosing but significant latency shifts in waves I and V of the brainstem auditory evoked response were evident. Following a subsequent dose adjustment, serum BR concentrations of approximately 400 mg/dL were associated with caudal paresis in two dogs. Estimated half-life during the accumulation phase was shorter than elimination half-lives reported in other studies and was likely related to dietary chloride content. The range of steady-state concentrations achieved suggests individual differences in clearance and bioavailability between dogs. The described protocol reliably produced serum BR concentrations that are required by many epileptic patients for satisfactory seizure control.

Administration, Oral↗

Interaction between pancuronium bromide and vecuronium bromide.

The interaction between two non-depolarizing neuromuscular blocking agents, pancuronium bromide and vecuronium bromide, has been studied at standardized levels of neuromuscular blockade and alternating the sequence of their administration, in 40 surgical patients. The drug administered first appeared invariably to play a dominant role in influencing both the dose requirements and the duration of action of the subsequent neuromuscular blocker. This resulted in reduced dose requirements and significant prolongation of action of vecuronium administered after pancuronium and increased dose requirements and shortening of neuromuscular blocking action of pancuronium given during vecuronium-induced partial neuromuscular blockade. Possible mechanisms of such interaction are discussed.

Adult↗

Uptake and excretion of vecuronium bromide and pancuronium bromide in the isolated perfused rat liver.

Using the isolated perfused rat liver preparation, the disappearance from the perfusate and the excretion in the bile of vecuronium bromide and pancuronium bromide and their metabolites were followed for 2 h after the addition of 1 mg of either drug to the perfusate. In addition, the rate of change of the hepatic content of these two compounds was calculated by serially subtracting the amount of the compound and the metabolites in the bile and in the perfusate from the dose of drug added to the perfusate. It was found that, whereas the concentration of pancuronium in the perfusate declined slowly and monoexponentially, vercuronium concentration in the perfusate declined rapidly in a biexponential manner. No metabolites of either drug were detected in the perfusate. Approximately 40% of the injected dose of vecuronium was excreted in the bile as unchanged vecuronium and another 30% as the 3-hydroxy metabolite. No other metabolites of vecuronium were found in the bile. In total only about 7% of pancuronium (unchanged) was collected in the bile by the end of the experiment. It is concluded that, in comparison to pancuronium, the rat liver takes up large amounts of vecuronium rapidly, half of which is eliminated as unchanged vecuronium and half as the 3-hydroxy derivative. A small amount of vecuronium or its 3-hydroxy metabolite is returned to the perfusate from the liver. Some possible mechanisms underlying these differences are discussed.

Animals↗

Effects of ethidium bromide, tetramethylethidium bromide and betaine B on the ultrastructure of HeLa cell mitochondria in situ. A comparative binding study.

Several investigators have described the ultrastructural changes that occur in the mitochondria of cells in tissue cultures after treatment with the drug ethidium bromide (E). The mitochondria swell and the cristae become greatly altered and finally disappear; in the cristae-free region of the matrix electron-dense granules can be observed. It has been assumed that intercalation of E between the base pairs of the mitochondrial DNA induces the formation of the granular inclusions. To investigate whether intercalation is really the initial step in the generation of dense granules inside the matrix, we performed a comparative incubation study of HeLa-cell mitochondria in situ using three closely related dyes (D), i.e., E, tetramethylethidium bromide (TME) and betaine B (B). They strongly differ with regard to their affinity for DNA and their ability to cross membranes. E was used as a reference dye. TME does not intercalate, but is externally bound to DNA only weakly. The neutral B is not bound at all, but can cross membranes more easily than the cation E. Moreover, in aqueous solutions at pH approximately equal to 7.0, B is in equilibrium with its protonated cation BH. BH and E have almost equal affinities for DNA. Therefore B may quickly pass the inner mitochondrial membranes and the cristae, and should then be bound inside the matrix, thus forming a BH-DNA complex. On the assumption that intercalation is necessary for the generation of intramitochondrial electron-dense bodies, we predicted that BH/B should be more efficient than E, while TME should be relatively ineffective.(ABSTRACT TRUNCATED AT 250 WORDS)

Betaine↗

Zinc triflate-benzoyl bromide: a versatile reagent for the conversion of ether into benzoate protecting groups and ether glycosides into glycosyl bromides.

A simple and efficient method is developed for the chemoselective one-pot conversion of ethers (benzyl, TBDMS and acetal) to the corresponding benzoates by zinc triflate-catalyzed deprotection and benzoylation by benzoyl bromide. In the same reaction, methyl or p-methoxyphenyl glycosides are converted into glycosyl bromides that are useful in glycosylation reactions.

Benzoates↗

Cationic liposomes in mixed didodecyldimethylammonium bromide and dioctadecyldimethylammonium bromide aqueous dispersions studied by differential scanning calorimetry, Nile Red fluorescence, and turbidity.

The thermotropic phase behavior of cationic liposomes in mixtures of two of the most investigated liposome-forming double-chain lipids, dioctadecyldimethylammonium bromide (DODAB) and didodecyldimethylammonium bromide (DDAB), was investigated by differential scanning calorimetry (DSC), turbidity, and Nile Red fluorescence. The dispersions were investigated at 1.0 mM total surfactant concentration and varying DODAB and DDAB concentrations. The gel to liquid-crystalline phase transition temperatures (Tm) of neat DDAB and DODAB in aqueous dispersions are around 16 and 43 degrees C, respectively, and we aim to investigate the Tm behavior for mixtures of these cationic lipids. Overall, DDAB reduces the Tm of DODAB, the transition temperature depending on the DDAB content, but the Tm of DDAB is roughly independent of the DODAB concentration. Both DSC and fluorescence measurements show that, within the mixture, at room temperature (ca. 22 degrees C), the DDAB-rich liposomes are in the liquid-crystalline state, whereas the DODAB-rich liposomes are in the gel state. DSC results point to a higher affinity of DDAB for DODAB liposomes than the reverse, resulting in two populations of mixed DDAB/DODAB liposomes with distinctive phase behavior. Fluorescence measurements also show that the presence of a small amount of DODAB in DDAB-rich liposomes causes a pronounced effect in Nile Red emission, due to the increase in liposome size, as inferred from turbidity results.

Calorimetry, Differential Scanning↗

Bromide intoxication by the combination of bromide-containing over-the-counter drug and dextromethorphan hydrobromide.

A 30-year old woman was presented to the emergency room with marked lethargy and fever. Her physical examination showed an acneiform eruption on the face. Blood biochemistry showed a high chloride level and a negative anion gap. High blood bromide level measurements on an ion-selective electrode was noted later to cause spurious hyperchloremia with a negative anion gap. After receiving saline hydration and diuretic treatment, her serum chloride returned to normal range on hospital day nine. Slow resolution of her mental status occurred over 2 months. Her skin lesions disappeared about 5 months later. In conclusion, in face of an unusual high chloride level and a negative anion gap in a patient of long-term use of over-the-counter (OTC) agents, bromide intoxication should be included in the differential diagnosis.

Adult↗

Liquid chromatographic determination of clidinium bromide and clidinium bromide-chlordiazepoxide hydrochloride combinations in capsules.

A specific liquid chromatographic method was developed for determination of clidinium bromide and clidinium bromide-chlordiazepoxide hydrochloride combinations in capsules. The procedure uses a Partisil 10 ODS-3 column and a mobile phase consisting of acetonitrile-0.3M ammonium phosphate (32 + 68) (pH = 4.3). The detection wavelength is 235 nm. Accuracy, reproducibility, and linearity were within accepted criteria. Four commercial samples of the single ingredient were tested; results compared favorably with the compendial method. Two commercial samples of the combination product were tested by the proposed method and results reported. The system was found to be free from any interferences from the 4 known related compounds of the 2 major components and is useful as a screening procedure for 7-chloro-1,3-dihydro-5-phenyl-2H-1,4-benzodiazepin-2-one-4-oxide, the principal degradation product of chlordiazepoxide hydrochloride.

Capsules↗

[Evaluation of the action of pipecuronium bromide in patients under halothane anesthesia--a comparison with pancuronium bromide regarding their neuromuscular blocking and cardiovascular effects].

Neuromuscular blocking and circulatory actions of pipecuronium bromide (PPB) were evaluated in patients under halothane-nitrous oxide-oxygen anesthesia in comparison with those of pancuronium bromide (PCB) in a multi-center cooperative study. Twitch tension of the adductor pollicis muscle was elicited by supramaximal stimulation of the ulnar nerve every 10 seconds. The study was performed according to the following 4 steps and the results were obtained. 1) Cumulative administration of 0.01 mg.kg-1 of PPB or PCB resulted in the potency ratio of 1.3:1.0 and the dose response curves of the two agents paralleled with each other. 2) With PPB 0.05 mg.kg-1 or 0.1 mg.kg-1, almost 100% block of the twitch was obtained. Both duration of action and the recovery time were shorter with 0.05 mg.kg-1 group. 3) After the first dose of 0.04 mg.kg-1 when the twitch recovered to 25% of the initial height 0.02 mg.kg-1 was given and this was repeated. Intervals between the doses showed large individual differences and no significant change was observed with repeated doses. 4) Safety of the drug. No significant change in heart rate or blood pressure was observed with PPB but with PCB a significant increase in heart rate was observed. The study revealed that PPB is slightly more potent than PCB and the duration of action is longer, but it has no untoward cardiovascular action in man under halothane anesthesia.

Adult↗

[Kinetic analysis of the action of cetyltrimethylammonium bromide on the membranes of the capsular variant of Escherichia coli CA189 recorded by ethidium bromide fluorescence].

A mathematical model, describing the kinetics of ethidium bromide probe fluorescence in the suspension of E. coli CA 189 capsular antigen after introduction of cetyltrimethylammonium bromide (a detergent), has been developed. Experimental testing of this mathematical model has confirmed that it describes the kinetics of the probe fluorescence augmentation sufficiently accurately. The new model permits the quantitative characterization of the rate of surfactant diffusion through the bacterial capsule.

Cell Membrane↗

[Comparison of the effects of ethidium bromide and of the ethidium bromide-deoxyribonucleic acid complex in Ehrlich tumor cells].

When injected into the peritoneal cavity, ethidium bromide can strongly inhibit the multiplication of mouse Ehrlich ascites tumour cells. This antitumour effect is increased when ethidium bromide is linked to DNA and also injected into the peritoneal cavity. The cellular alterations are identical after a treatment with E.B. either free or bound to DNA. However, when the cells are treated with E.B.-DNA they contain E.B. for a longer period than after a treatment with E.B.

Animals↗

Oxytropium bromide in bronchial asthma: comparison of metered dose inhaler and powder inhalation of the anticholinergic bronchodilator oxytropium bromide in protection against acetylcholine and histamine provocation.

A marked protective effect of 0.2 mg oxytropium bromide (Ba 253), administered by inhalation, was observed against experimental provocation with a 3% acetylcholine solution. There is no difference between application by means of a metered dose inhaler or by means of powder inhalation. There is no marked protective effect of 0.2 mg oxytropium bromide administered by inhalation (aerosol or powder) against experimental provocation with a 0.3% histamine solution.

Acetylcholine↗

Bromide space determination using anion-exchange chromatography for measurement of bromide.

A high-pressure liquid chromatographic method for bromide measurement is used to determine extracellular water volume in humans. The method uses 5 microL serum ultrafiltrate and has a sensitivity of 7.5 pmol. Because of the extreme sensitivity of this method, relatively small quantities of Br can be administered and small amounts of blood are needed for the analysis. By this method, the mean corrected Br space in 82 healthy adults representing a wide range of body weights was 0.218 +/- .034 L/kg (mean +/- 1 SD) with a range of 0.153-0.295 L/kg, which is consistent with reported values. There was a significant, inverse relationship between corrected Br space per kilogram and obesity as measured by body mass index. The corrected Br space in six children aged 3-36 mo was 0.335-0.394 L/kg, which is also consistent with reported values in children of this age. This method for Br measurement can easily and readily be applied for the determination of extracellular water volume.

Adult↗

1-[(4-Chlorobenzoyl)methyl]-4-(N,N-dimethylamino)pyridinium bromide sesquihydrate and 1-[(4-bromobenzoyl)methyl]-4-(N,N-dimethylamino)pyridinium bromide sesquihydrate.

The title compounds, C15H16ClN2O+.Br-.1.5H2O and C15H16BrN2O+.Br-.1.5H2O, are isomorphous. The benzene ring is oriented nearly normal to the pyridine ring in both compounds. The molecular packing is mainly influenced by intermolecular O-H...O and O-H...Br interactions, as well as weak intramolecular C-H...O interactions. The H2OBr- units form an extended water-bromide chain, with a bridging water molecule on a twofold axis.

4-Aminopyridine↗

Structure of tetraaquacobalt(II) bromide dihydrate (cobalt bromide hexahydrate).

Tetraaquacobalt(II) bromide dihydrate, [Co(H2O)4]Br2 x 2H2O, Mr = 326.83, monoclinic, C2/m, a = 11.0158(12), b = 7.1694(10), c = 6.9111(10) A, beta = 124.761(7)degrees, V = 448.4(1) A3, Z = 2, F(000) = 314, Dx = 2.420 g cm-3, lambda(Mo K alpha) = 0.71069 A, T = 296 K, mu = 107.13 cm-1, R = 0.022 for 532 unique reflections having I greater than 0. The single type of Co ion is octahedrally coordinated by four equivalent water-molecule O atoms at the observed distance 2.081(2) A and two equivalent Br ions at the observed distance 2.6048(5) A in an array which, with respect to its angles, departs only slightly from regular octahedral geometry. The cobalt-oxygen-bromine complex was found to manifest rigid-body behavior. The cobalt-oxygen distance corrected for rigid-body motion was found to be 2.088 A; the corrected cobalt-bromine distance, 2.6081 A. Associated with each complex are two water molecules of hydration. Assignment and refinement of the coordinates of the four non-equivalent H atoms permitted detailed analysis of the hydrogen bonding, which involves each of the four non-equivalent H atoms significantly. The structure as determined in this study differs markedly from that presented in the sole published single-crystal study [Stroganov, Andreev, Kozina & Solov'ev (1961). Vestn. Leningr. Univ. Ser. Mat. Fiz. Khim. 16, 114-119]. In particular, the space-group assignment differs and the pattern of bromine-oxygen distances is quite different. Contrary to Stroganov et al., this structure is isomorphic with that of cobalt chloride hexahydrate.

Bromides↗