Validation of an HPLC analytical method for determination of pancuronium bromide in pharmaceutical injections

Pancuronium bromide is used with general anesthesia in surgery for muscle relaxation and as an aid to intubation. A high performance liquid chromatographic method was fully validated for the quantitative determination of pancuronium bromide in pharmaceutical injectable solutions. The analytical method was performed on an amino column (Luna 150mm4.6mm, 5m). The mobile phase was composed of acetonitrile:water containing 50mmol L-1 of 1-octane sulfonic acid sodium salt (20:80v/v) with a flow rate of 1.0mL min-1 and ultraviolet (UV) detection at 210nm. The proposed analytical method was compared with that described in the British Pharmacopoeia.

Effects of paralysis with pancuronium bromide on joint mobility in premature infants.

To study the effects of muscle paralysis on joint mobility, we compared eight premature infants treated with pancuronium bromide with a control group. A significant reduction was observed in hip and knee flexion, and in ankle dorsal extension, which tended to resolve in time. We conclude that muscle paralysis reduces the mobility of selected joints; spontaneous activity appears to prevent long-term contractures.

Paralysis of ventilated newborn babies does not influence resistance of the total respiratory system.

Paralysis with pancuronium bromide is used in newborn infants to facilitate ventilatory support during respiratory failure. Changes in lung mechanics have been attributed to paralysis. The aim of this study was to examine whether or not paralysis per se has an influence on the passive respiratory mechanics, resistance (Rrs) and compliance (Crs) of the respiratory system in newborn infants. In 30 infants with acute respiratory failure, Rrs was measured during paralysis with pancuronium bromide and after stopping pancuronium bromide (group A). Rrs was also measured in an additional 10 ventilated infants in a reversed fashion (group B): Rrs was measured first in nonparalysed infants and then they were paralysed, mainly for diagnostic procedures, and the Rrs measurement repeated. As Rrs is highly dependent on lung volume, several parameters, that depend directly on lung volume were recorded: inspiratory oxygen fraction (FI,O2), arterial oxygen tension/alveolar oxygen tension (a/A) ratio and volume above functional residual capacity (FRC). In group A, the Rrs was not different during (0.236+/-0.09 cmH2O x s x mL(-1)) and after (0.237+/-0.07 cmH2O x s x mL(-1)) paralysis. Also, in group B, Rrs did not change (0.207+/-0.046 versus 0.221+/-0.046 cm x s x mL(-1) without versus with pancuronium bromide). FI,O2, a/A ratio and volume above FRC remained constant during paralysis. These data demonstrate that paralysis does not influence the resistance of the total respiratory system in ventilated term and preterm infants when measured at comparable lung volumes.

Comparison of a sidestream capnograph and a mainstream capnograph in mechanically ventilated dogs

Objective-To compare the ability of a sidestream capnograph and a mainstream capnograph to measure end-tidal CO2 (ETCO2) and provide accurate estimates of Paco(2) in mechanically ventilated dogs.Design-Randomized, double Latin square.Animals-6 healthy adult dogs.Procedure-Anesthesia was induced and neuromuscular blockade achieved by IV administration of pancuronium bromide. Mechanical ventilation was used to induce conditions of standard ventilation, hyperventilation, and hypoventilation. While tidal volume was held constant, changes in minute volume ventilation and Paco(2) were made by changing the respiratory rate. Arterial blood gas analysis was performed and ETCO2 measurements were obtained by use of either a mainstream or a sidestream capnographic analyzer.Results-A linear regression model and bias analysis were used to compare Paco(2) and ETCO2 measurements; ETCO2 measurements obtained by both capnographs correlated well with Paco(2). Compared with Paco(2), mainstream ETCO2 values differed by 3.15 +/- 4.89 mm Hg (mean bias +/- SD), whereas the bias observed with the sidestream ETCO2 system was significantly higher (5.65 +/- 5.57 mm Hg). Regardless of the device used to measure ETCO2, bias increased as Paco(2) exceeded 60 mm Hg.Conclusions and Clinical Relevance-Although the mainstream capnograph was slightly more accurate, both methods of ETCO2 measurement correlated well with Paco(2) and reflected changes in the ventilatory status. However, ETCO2 values > 45 mm Hg may inaccurately reflect the severity of hypoventilation as Paco(2) may be underestimated during conditions of hypercapnia (Paco(2) > 60 mm Hg).

Anestesia peribulbar com ropivacaína como alternativa ao bloqueio neuromuscular para facectomia em cães

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Determination of Vecuronium Bromide in Pharmaceuticals: Development, Validation and Comparative Study of HPLC and CZE Analytical Methods

Vecuronium bromide is a neuromuscular blocking agent used for anesthesia to induce skeletal muscle relaxation. HPLC and CZE analytical methods were developed and validated for the quantitative determination of vecuronium bromide. The HPLC method was achieved on an amino column (Luna 150 x 4.6 mm, 5 mu m) using UV detection at 205 nm. The mobile phase was composed of acetonitrile:water containing 25.0 mmol L(-1) of sodium phosphate monobasic (50:50 v/v), pH 4.6 and flow rate of 1.0 mL min(-1). The CZE method was achieved on an uncoated fused-silica capillary (40.0 cm total length, 31.5 cm effective length and 50 mu m i.d.) using indirect UV detection at 230 nm. The electrolyte comprised 1.0 mmol L(-1) of quinine sulfate dihydrate at pH 3.3 and 8.0% of acetonitrile. The results were used to compare both techniques. No significant differences were observed (p > 0.05).

[effect Of Ropivacaine Combined With Pancuronium On Neuromuscular Transmission And Effectiveness Of Neostigmine And 4-aminopyridine For Blockade Reversal: Experimental Study].

The local anesthetic effects on neuromuscular junction and its influence on blockade produced by nondepolarizing neuromuscular blockers are still under-investigated; however, this interaction has been described in experimental studies and in humans. The aim of this study was to evaluate in vitro the interaction between ropivacaine and pancuronium, the influence on transmission and neuromuscular blockade, and the effectiveness of neostigmine and 4-aminopyridine to reverse the blockade. Rats were divided into groups (n=5) according to the study drug: ropivacaine (5μgmL(-1)); pancuronium (2μg.mL(-1)); ropivacaine+pancuronium. Neostigmine and 4-aminopyridine were used at concentrations of 2μgmL(-1) and 20μgmL(-1), respectively. The effects of ropivacaine on membrane potential and miniature end-plate potential, the amplitude of diaphragm responses before and 60minutes after the addition of ropivacaine (degree of neuromuscular blockade with pancuronium and with the association of pancuronium-ropivacaine), and the effectiveness of neostigmine and 4-aminopyridine on neuromuscular block reversal were evaluated. Ropivacaine did not alter the amplitude of muscle response (the membrane potential), but decreased the frequency and amplitude of the miniature end-plate potential. Pancuronium blockade was potentiated by ropivacaine, and partially and fully reversed by neostigmine and 4-aminopyridine, respectively. Ropivacaine increased the neuromuscular block produced by pancuronium. The complete antagonism with 4-aminopyridine suggests presynaptic action of ropivacaine.

Use of lignin extracted from different plant sources as standards in the spectrophotometric acetyl bromide lignin method

A nongravimetric acetyl bromide lignin (ABL) method was evaluated to quantify lignin concentration in a variety of plant materials. The traditional approach to lignin quantification required extraction of lignin with acidic dioxane and its isolation from each plant sample to construct a standard curve via spectrophotometric analysis. Lignin concentration was then measured in pre-extracted plant cell walls. However, this presented a methodological complexity because extraction and isolation procedures are lengthy and tedious, particularly if there are many samples involved. This work was targeted to simplify lignin quantification. Our hypothesis was that any lignin, regardless of its botanical origin, could be used to construct a standard curve for the purpose of determining lignin concentration in a variety of plants. To test our hypothesis, lignins were isolated from a range of diverse plants and, along with three commercial lignins, standard curves were built and compared among them. Slopes and intercepts derived from these standard curves were close enough to allow utilization of a mean extinction coefficient in the regression equation to estimate : lignin concentration in any plant, independent of its botanical origin. Lignin quantification by use of a common regression equation obviates the steps of lignin extraction, isolation, and standard curve construction, which substantially expedites the ABL method. Acetyl bromide lignin method is a fast, convenient analytical procedure that may routinely be used to quantify lignin.

Drug use evaluation of ipratropium bromide at two tertiary referral hospitals in Brisbane.

Objective: To assess the appropriateness of ipratropium bromide prescribing in two tertiary referral hospitals. Method: Criteria for optimal use were developed based on current literature and modified after consultation with respiratory physicians and clinical pharmacists. A prospective review of prescribing was performed over a 2-month period to assess conformity to these criteria. Results: Information was collected from 84 patients; 5% were receiving inhalers and 96% nebuliser therapy (one patient used both). 77% of patients (n = 65) had a principal diagnosis of chronic obstructive pulmonary disease, 14% (n = 12) asthma and 8% (n = 7) had neither diagnosis. 75% of patients were using ipratropium outside the guidelines. The major areas where the guidelines were not met were a lack of therapeutic justification, use of inappropriate doses, and use of an inappropriate delivery device. Feedback and educational interventions were designed and delivered based on the data obtained. Conclusions: There was widespread use of ipratropium outside the developed guidelines. Interventions in specific areas could lead to significant improvements in the use of this high cost drug

Reversible Photorheology in Solutions of Cetyltrimethylammonium Bromide, Salicylic Acid, and trans-2,4,4 '-Trihydroxychalcone

We show photorheology in aqueous solutions of weakly entangled wormlike micelles prepared with cetyltrimethylammonium bromide (CTAB), salicylic acid (HSal), and dilute amounts of the photochromic multistate compound trans-2,4,4'-trihydroxychalcone (Ct). Different chemical species of Ct are associated with different colorations and propensities to reside within or outside CTAB micelles. A light-induced transfer between the intra- and intermicellar space is used to alter the mean length of wormlike micelles and hence the rheological properties of the fluid, studied in steady-state shear Bow and in dynamic rheological measurements. Light-induced changes of fluid rheology are reversible by a the relaxation process. at relaxation rates which depend on pH and which are consistent with photochromic reversion rates measured by UV-vis absorption spectroscopy. Parameterizing viscoelostic rheological states by their effective relaxation time tau(c) and corresponding response modulus G(c), we find the light and dark states of the system to fall onto a characteristic state curve defined by comparable experiments conducted without photosensitive components. These reference experiments were prepared with the same concentration of CTAB, but different concentrations of HSal or sodium salicylote (NaSal), and tested at different temperatures.

Reduction of QTc interval dispersion. Potential mechanism of cardiac protection of pyridostigmine bromide

OBJECTIVE: Parasympathetic dysfunction is an independent risk factor in individuals with coronary artery disease, and cholinergic stimulation is a potential therapeutical option. We determined the effects of pyridostigmine bromide, a reversible anticholinesterase agent, on electrocardiographic variables of healthy individuals. METHODS: We carried out a cross-sectional, double blind, randomized, placebo-controlled study. We obtained electrocardiographic tracings in 12 simultaneous leads of 10 healthy young individuals at rest before and after oral administration of 45 mg of pyridostigmine or placebo. RESULTS: Pyridostigmine increased RR intervals (before: 886±27 ms vs after: 1054±37 ms) and decreased QTc dispersion (before: 72±9ms vs after: 45±3ms), without changing other electrocardiographic variables (PR segment, QT interval, QTc, and QT dispersion). CONCLUSION: Bradycardia and the reduction in QTc dispersion induced by pyridostigmine may effectively represent a protective mechanism if these results can be reproduced in individuals with cardiovascular diseases.

Reversible and irreversible pollutant-induced bacterial cellular stress effects measured by ethidium bromide uptake and efflux.

Chemical pollution is known to affect microbial community composition but it is poorly understood how toxic compounds influence physiology of single cells that may lay at the basis of loss of reproductive fitness. Here we analyze physiological disturbances of a variety of chemical pollutants at single cell level using the bacterium Pseudomonas fluorescens in an oligotrophic growth assay. As a proxy for physiological disturbance we measured changes in geometric mean ethidium bromide (EB) fluorescence intensities in subpopulations of live and dividing cells exposed or not exposed to different dosages of tetradecane, 4-chlorophenol, 2-chlorobiphenyl, naphthalene, benzene, mercury chloride, or water-dissolved oil fractions. Because ethidium bromide efflux is an energy-dependent process any disturbance in cellular energy generation is visible as an increased cytoplasmic fluorescence. Interestingly, all pollutants even at the lowest dosage of 1 nmol/mL culture produced significantly increased ethidium bromide fluorescence compared to nonexposed controls. Ethidium bromide fluorescence intensities increased upon pollutant exposure dosage up to a saturation level, and were weakly (r(2) = 0.3905) inversely correlated to the proportion of live cells at that time point in culture. Temporal increase in EB fluorescence of growing cells is indicative for toxic but reversible effects. Cells displaying high continued EB fluorescence levels experience constant and permanent damage, and no longer contribute to population growth. The procedure developed here using bacterial ethidium bromide efflux pump activity may be a useful complement to screen sublethal toxicity effects of chemicals.