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At least 19 recordsLinked to original sources
PubMed1998

Effect of pH on the stability of methacholine chloride in solution.

Methacholine chloride bronchoprovocation challenges are performed for the diagnosis and investigation of hyperreactive airways. Over the last 20 yrs various formulations and pH values for the preparation of solutions of methacholine have been described. To determine the stability of methacholine chloride solutions prepared in a variety of buffers with differing pH values and under varying storage temperatures, we measured methacholine concentrations at intervals from 1 to 5 weeks. It was found that methacholine chloride solutions rapidly decompose if the pH is greater than 6 and that decomposition is more rapid as the pH is raised; solutions at pH 9, i.e. bicarbonate buffer, and stored at 27 degrees C have degradation up to 36% after only one week. Solutions of the same pH but prepared in different buffers can have both varied rates of deterioration and different absolute amounts of methacholine hydrolysed, e.g. solutions prepared in pH 9 borate buffer and stored at 27 degrees C have up to 60% degradation after 1 week. Solutions prepared in saline are stable probably because methacholine solutions are weakly acidic. The results emphasise the importance of preparing methacholine chloride in the proper buffers for use in the accurate assessment of airway responsiveness.

Bronchoconstrictor Agents↗
PubMed1982

Stability of stored methacholine chloride solutions: clinically useful information.

Methacholine inhalation challenge (MIC) has been shown to be an extremely useful diagnostic test. Because a decrease in the time and expense involved in the preparation of methacholine chloride solutions might encourage more laboratories to perform MIC, we assessed the stability of several different concentrations of methacholine chloride in solution over a period of 4 months. We used and compared 2 different assay techniques: a high pressure liquid chromatography assay and a colorimetric assay. Comparable results were obtained by both assays and demonstrated that methacholine solutions stored either at room temperature or at 4 degrees C showed no significant decomposition over a period of 4 months. From our results, we conclude that: (1) methacholine chloride solutions are much more stable than stated in the Merck Manual, (2) the original data of MacDonald and coworkers on the stability of methacholine chloride solution are accurate, (3) our high pressure liquid chromatography method is an accurate and highly specific technique for measuring methacholine chloride solutions. The major clinical implication of our results is that the time and cost necessary to prepare methacholine chloride solutions is much less than previously thought. This should encourage a more widespread use of this important diagnostic technique for the demonstration of bronchial hyperreactivity.

Chromatography, High Pressure Liquid↗
PubMed1983

Preparation and handling of methacholine chloride testing solutions. Effect of the hygroscopic properties of methacholine.

Persons with hyperreactive airways differ quantitatively from normal persons in their response to bronchial provocation testing with methacholine chloride (Mch). Methacholine chloride has strong hygroscopic properties that necessitate careful dessication, preparation, and handling if accurate results are to be achieved. The rate of hydration of Mch was determined by exposing the drug to various levels of relative humidity. The rate of water uptake was directly related to the availability of water in the atmosphere. At 49% relative humidity, a 0.125%/min gain in weight was noted, which increased to 0.489%/min at 80% relative humidity. Adequate dessication time and technique were determined by noting the time required to return the drug from a hydrated to a dry state. With proper technique, dessication was virtually complete by 4 to 6 h, and 20 to 24 h assured a return to the dry state. From these data, guidelines for preparation and handling of Mch test solutions can be formulated.

Bronchial Provocation Tests↗
PubMed1998

Stability of methacholine chloride solutions under different storage conditions over a 9 month period.

Methacholine chloride solutions, routinely used for testing bronchial hyperreactivity, have been shown to degrade over time. The data published addressing the optimal conditions for methacholine chloride storage are conflicting and incomplete. This study investigated the effects of a variety of conditions on the stability of methacholine chloride. Methacholine chloride, dissolved in phosphate buffered saline (PBS) or sodium chloride (NaCl) at 50 and 0.39 g x L(-1), was subjected to various light and temperature conditions for 9 months. Methacholine chloride degradation was determined by high performance liquid chromatography, and all solutions underwent bacterial and pH testing. By 9 months, all 50 g x L(-1) solutions of methacholine chloride had degraded by 65+/-0.8%. All 0.39 g x L(-1) solutions in NaCl had degraded by 11.0+/-0.33%. The 0.39 g x L(-1) solutions in PBS which had been frozen, refrigerated or stored at room temperature had degraded by 8.0%, 16.0+/-0.3% and 63.8+/-0.5%, respectively. The pH of methacholine chloride was 7.2 in PBS at 0.39 g x L(-1), 5.8 in PBS at 50 g x L(-1), 3.9 in NaCl at 0.39 and 2.7 in NaCl at 50 g x L(-1). Bacterial contamination was minimal. The results of this study demonstrate that methacholine chloride is more stable at the higher concentration. However, the pH of the more concentrated solutions of methacholine chloride in sodium chloride could cause bronchoconstriction in some subjects. We therefore recommend storing methacholine chloride at 50 g x L(-1) in phosphate-buffered saline.

Bronchoconstrictor Agents↗
PubMed1999

Stability of methacholine chloride in isotonic sodium chloride using a capillary electrophoresis assay.

OBJECTIVE: To investigate the stability of methacholine chloride in 0.9% sodium chloride solutions. METHOD: Methacholine powder was mixed with diluent to a final concentration of 5 and 10 mg/ml. Duplicates of each admixture were divided and stored in glass vials at 25 degrees C, 4 degrees C and -20 degrees C for 12 months. At appropriate times intervals, samples were removed from solutions and analysed. Methacholine concentrations were measured using a high performance capillary electrophoresis assay. RESULTS: No colour or other visual changes were seen in any sample. However, an additional peak was observed in some samples. CONCLUSION: Methacholine chloride solutions 5 mg/ml were stable in isotonic sodium chloride after refrigeration or freezing over a period of one year; methacholine chloride solutions 10 mg/ml were stable for one year after freezing. The solutions stored at ambient temperature were stable for 35 days and for less than 14 days, respectively, for the 5 and the 10 mg/ml solutions.

Bronchoconstrictor Agents↗
PubMed1981

Stability of methacholine chloride in bronchial provocation test solutions.

The stability of methacholine chloride (5 mg/ml) in 0.9% sodium chloride solution was measured. A reliable colorimetric assay (530 nm) based on the formation of a hydroxamic acid-iron complex was used. At appropriate time intervals, samples were removed from solutions stored at 4, 20, 37, 60, or 80 degrees C and assayed. The degradation of methacholine chloride followed apparent first-order kinetics of methacholine chloride followed apparent first-order kinetics at all temperatures, with observed half-lives ranging from 29.3 days at 80 degrees C to 693 days 4 degrees C. Methacholine chloride in 0.9% sodium chloride solution does not degrade as rapidly as previously suggested. According to an Arrhenius plot, storage of such solutions at 30 or 4 degrees C would result in not more than 10% degradation over a period of approximately two or five months, respectively. Thus, it should be possible to prepare stock solutions of this deliquescent drug.

Bronchial Provocation Tests↗
PubMedDate not supplied

Effect of a single dose of montelukast sodium on methacholine chloride PC20.

BACKGROUND: It is currently recommended that leukotriene modifiers (receptor antagonists and synthesis inhibitors) be withheld for a minimum of 24 h before direct bronchoprovocation testing, but there is little evidence to support this recommendation. OBJECTIVE: To examine the effect of a single oral dose of montelukast sodium 10 mg on airway response to methacholine chloride-induced bronchoconstriction. METHODS: A double-blind, placebo-controlled, randomized crossover trial was performed in 12 subjects with asthma whose methacholine chloride concentration causing a 20% decrease in the forced expiratory volume during the first second of exhalation (PC20) was 8 mg/mL or lower and a baseline forced expiratory volume during the first second of exhalation of 70% predicted or greater. Two-minute tidal breathing methacholine chloride inhalation challenges were performed 1 h and 25 h after both 10 mg montelukast sodium and identical-appearing placebo. RESULTS: There were no significant differences in the methacholine chloride PC20 between active treatment and placebo at 1 h post-10 mg montelukast sodium (1.0 mg/mL versus 1.3 mg/mL; n=12; P=0.17, respectively) or at 25 h post-10 mg montelukast sodium (1.4 mg/mL versus 1.9 mg/mL; n=11; P=0.15, respectively). CONCLUSION: A single dose of montelukast sodium did not affect methacholine chloride-induced bronchoconstriction measured after 1 h and 25 h.

Acetates↗
PubMed1979

Effect of methacholine chloride on rheology and transport of canine tracheal mucus.

The effect of methacholine chloride (M) on tracheal mucus was investigated in three conscious tracheostomized dogs. Aerosols of M in concentrations of 2--32 mg/ml were delivered intratracheally for 1 min. Mucus was sampled with a cytology brush at 2 min postchallenge and at irregular intervals thereafter. The mechanical properties of each sample were determined in the magnetic microrheometer, and correlated with mucociliary transportability as assayed by the frog palate technique. With high doses of M, there was an increase in volume of secretion collected per unit time. The elastic modulus (G') at 2 min postchallenge went up (to 1.5 x 2.3 x control for 16 and 32 mg/ml, respectively) then fell below control before returning to base line after 30 or 45 min. With low doses of M (2--8 mg/ml) the secretion rate was also above control, but only a decrease in G' (to 0.54 x control) was observed. The decrease in G' at low doses did not significantly alter the frog palate transport rate; however, the increase at higher doses did impede mucociliary transport.

Animals↗
PubMed2003

An in vitro study to investigate the use of a breath-actuated, small-volume, pneumatic nebulizer for the delivery of methacholine chloride bronchoprovocation agent.

BACKGROUND: Current American Thoracic Society and American Association for Respiratory Care guidelines for the delivery of aerosol agents such as methacholine chloride (MC) for bronchoprovocation testing require the use of pneumatic jet nebulizers that have well-defined droplet size and mass output. A recently developed disposable, breath-actuated nebulizer (AeroEclipse) may offer bronchoprovocation testers an alternative to existing devices. METHODS: We studied the performance of 5 AeroEclipse nebulizers with regard to mass of MC delivered with various MC solution concentrations and numbers of inhalations, using a model of adult tidal breathing. Each nebulizer was operated with compressed air (8 L/min at 50 psig) and an initial fill of 2 mL. MC solutions with mass concentrations of 0.25, 0.98, 3.85, and 15.70 mg/mL were tested. The total mass of MC delivered was determined after 5, 10, and 15 complete breathing cycles, by assaying the MC collected on a filter placed at the nebulizer mouthpiece. The aerosol droplet size distribution, fine droplet fraction (FDF) (percentage of droplets < 4.8 microm diameter), and fine droplet mass (FDM) (mass of droplets < 4.8 microm diameter) were determined by laser diffractometry, using physiologically normal saline as a surrogate for MC solution. RESULTS: The mean +/- SD FDM collected in 5 breathing cycles was 654 +/- 29 microg with the 15.70 mg/mL solution, 158 +/- 9 microg with the 3.85 mg/mL solution, 37 +/- 3 microg with the 0.98 mg/mL solution, and 7 +/- 2 microg with the 0.25 mg/mL solution. FDM showed a linear correlation (r(2) = 0.9999) with MC concentration, within the range studied. FDM also showed a linear correlation (r(2) = 0.999) with the number of breathing cycles. For instance, with the 15.70 mg/mL solution, FDM was 654 +/- 29 microg with 5 breathing cycles, 1,228 +/- 92 microg with 10 breathing cycles, and 1,876 +/- 132 microg with 15 breathing cycles. CONCLUSIONS: Although the bronchoprovocation test procedure had to be slightly modified from the guidelines to accommodate the operation of the AeroEclipse's breath-actuation feature, our measurements indicate that a predictable dose of MC, within the useful range for bronchoprovocation testing, can be delivered to an adult patient breathing tidally. The green indicator on the AeroEclipse could be used to coach the patient to inhale for a specific period, thereby controlling MC delivery per breathing cycle.

Adult↗
PubMed1980

Simultaneous comparison of canine tracheal transport of anion exchange resin particles to albumin macroaggregates and sulfur colloid. Effects of subcutaneous methacholine chloride and intravenous hypertonic saline.

We compared simultaneously measured canine tracheal transport rates of Dowex anion exchange particles with macroaggregates of albumin, and with sulfur colloid. We found that sulfur colloid moved significantly faster than large Dowex particles (diameter 180 micrometer), which had transport rates similar to macroaggregates of albumin, and small Dowex particles diameter 3 micrometer). We examined the alteration of airway fluid caused by intravenous 5% saline or subcutaneous methacholine chloride. We then studied the effects of the altered airway fluid on the transport rates of large Dowex particles and sulfur colloid. We found that sulfur colloid continued to be transported faster than Dowex particles. Although we do not have an explanation for the faster transport of sulfur colloid, we believe that the physiochemical properties of the marker may influence its rate of tracheal transport.

Albumins↗
PubMed2001

Stability of stored methacholine solutions: study of hydrolysis kinetic by IP-LC.

Methacholine chloride is a powerful cholinergic bronchoconstrictor agent used during bronchial airway hyper-responsiveness diagnosis. Methacholine is susceptible to hydrolysis in aqueous solutions in acetic acid and beta-methylcholine. In the present work, kinetics of hydrolysis with different solvents (water and phosphate-buffered saline (PBS) pH 7.4) at different temperatures have been studied using a newly developed high-performance liquid chromatography. At 4 degrees C, kinetic determination of hydrolysis in methacholine chloride solutions (50 mg/ml) shows no hydrolysis in either aqueous or phosphate-buffered solutions over a 40-day period. At 30 degrees C, concentration of unbuffered methacholine chloride solutions remained unchanged, but buffered methacholine chloride solutions have degradation up to 5.5% over a 40-day period. At 40 degrees C, concentration of unbuffered methacholine chloride has degradation up to 5% and buffered methacholine chloride solutions have degradation up to 10% over a 40-day period. Methacholine chloride solutions are susceptibly to be used in hospital pharmacy at different concentrations. We have studied pH and osmolality for methacholine solutions prepared with different diluents potentially used in hospital pharmacies, i.e. deionized water, 0.9% NaCl and PBS pH 7.4. We have demonstrated that methacholine solutions prepared with deionized water at 50 mg/ml and diluted with PBS pH 7.4 from 5 to 40 mg/ml are isoosmotic and potentially available for inhalation tests to measure non-specific bronchial hyper-responsiveness.

Bronchoconstrictor Agents↗
PubMed1987

Proteins are secreted from heterogeneous prestored sources in the exocrine pancreas.

Recent studies demonstrating nonparallel regulated secretion of prestored digestive enzymes in tightly linked groups consistent with the exocytosis mechanism led us to predict that digestive enzymes would be found to be secreted from heterogeneous sources within the exocrine pancreas (J. W. Adelson, and P.E. Miller, Science Wash. DC 228: 993-996, 1985). We explored whether the gland was heterogeneous with respect to its sources of prestored secretory proteins with a double isotopic label method not dependent on activity of secreted digestive enzymes. Rabbit pancreatic proteins were double labeled in vivo by injection of each animal with chemically identical but isotopically distinct mixtures of 3H- and 14C-labeled amino acids, which were administered separately or together on consecutive days after partial depletion of prestored proteins by administration of cholecystokinin (CCK), methacholine chloride, or saline in a protocol in which order of both isotope and secretagogue administration was varied. Three days after labeling, proteins were recovered by collection from cannulated pancreatic ducts of anesthetized animals after stimulation with alternating increasing doses of CCK and methacholine chloride. Pooled secretory data were analyzed to determine whether secretagogue pretreatment resulted in specific and heterogeneous sequestration of proteins after synthesis; data after final secretory stimulation with methacholine chloride and CCK were individually analyzed to determine whether presequestered proteins were mobilized from heterogeneous compartments during secretion. Correlation and regression analysis of isotopic outputs and variance analysis of specific radioactivities of secreted proteins showed sequestration into and secretion from heterogeneous pools of secretory proteins, directly confirming out hypothesis. These results provide a cell biological mechanism explaining regulated nonparallel secretion of digestive enzymes.

Animals↗
PubMed1975

Chronic cholinergic stimulation of canine respiratory tissue. Its effect on the activities of glycosyltransferases and release of macromolecules.

The influence of cholingergic stimulation on the incorporation of D-[6-3H]glucosamine into macromolecules released by canine trachea in vitro, and the capacity of subcellular fraction of this tissue to catalyze the transfer of various sugars to specific glycoproteins were measured. Canine trachea was incubated with radiohexosamine for 18 hours in the presence of methacholine chloride. The [3H]macromolecules subsequently released were fractionated on columns of 1 per cent agarose. Those macromolecules eluted from the columns with a mobility identical to that of large molecular weight, mucin-type glycoproteins of canine tracheal pouch secretions collected in vivo were increased. The tissue then did not respond to further challenges with acetylcholine chloride, at least as regards the release of radiomacromolecular. In addition, in vitro challenges of methacholine chloride failed to alter the specific activities of the tracheobronchial tissue glycosyltransferases. The specific activities of 2 galactosyltransferases, a sialytransferase, and an N-acetylgalactosaminyltransferase were elevated after 1 month and after 2 months of daily subcutaneous injections of methacholine chloride. No further increases were seen during the third month of injections; throughout the 3 months, the specific activity of fucosyltransferase failed to change.

Acetylcholine↗