The use of osmometry as a means of determining changes in drug concentration during jet nebulization

In the treatment of cystic fibrosis (CF), more and more medications (i.e., aminoglycoside antibiotics, bronchodilators) are being administered by air jet nebulization. Therefore, in order to determine appropriate dosages for individual patients, drug output of a nebulizer must be predetermined. The ability to accurately predict drug output, however, becomes highly dependent on the accuracy of the method of drug analysis. As jet nebulization proceeds, concentration of the drug in the nebulizer increases due to evaporative losses. In order to determine the degree to which this occurs, it is necessary to be able to measure the concentration of the active agent in the nebulizer. This can be done directly by chemical analysis (e.g., ultraviolet [UV] spectrophotometry) or indirectly by osmometry. These two methods were compared. Using both a Hudson 1720 "T" Up-Draft Neb-U-Mist (Hudson Inc., Temecula, CA) and a Hudson 1730 "T" Up-Draft Neb-U-Mist II jet nebulizer, different drug preparations commonly used in CF therapy were run at a calibrated flow of 6 L/min for predetermined times and pre-and post samples were taken to evaluate the degree of concentration. Three different preparations, albuterol, tobramycin, and a combination of the two, were used. UV spectrophotometry for albuterol involved precision dilutions and therefore was slightly more labor-intensive than osmometry. The UV spectrophotometric analysis for tobramycin required a derivatization procedure which was extremely labor-intensive. The Bland and Altman test of limits of agreement showed good agreement between the two methods. Also, due to numerous steps involved in the UV spectrophotometric method, the variability of repeat measurements was much higher (3.0% relative standard deviation [RSD]) than for osmometry (0.7% RSD), In conclusion, this investigation showed that osmometry may be used as a proxy for the more specific UV spectrophotometric analysis in determining drug concentrations for both albuterol preparations and the parenteral preparation of tobramycin.