I N D U S T R I A L A N D E N G I N E E R I N G CHEMISTRY
32
All concentrations and blank corrections were determined by the least squares method applied to a number of samples of the potassium iodide solution requiring different volumes of mercuric nitrate or silver nitrate. A typical set of such data is that for the mercurimetric determination of the concentration of potassium iodide solution, given in Table I. TABLE I. MERCURIMETRIC ANALYSISOF POTASSIUM IODIDE SOLUTION Volume of KI S o h .
cc.
kinetic investigations this method has been found accurate, rapid, and more convenient than the Volhard method.
Acknowledgment The author acknowledges his indebtedness to L. P. Hammett for helpful guidance in the course of this investigation, and to H. T. Beans for various suggestions.
Literature Cited
Hg(N0;)r Titer%b
cc.
The agreement of these results indicates that the mercurimetric method is reliable under the conditions employed here. The use of peroxide-free dioxane may be a cumbersome and undesirable essential in occasional iodide determinations; however, for frequent routine analyses of iodide solutions in
Vol. 14, No. 1
(1) Beste, G. W., and Hammett, L. P., J. Am. Chem. Soc., 62, 2481 (1940). ENG.CHEM.,ANAL.ED., (2) Caldwell, J. R., and Moyer, H. V., IND. 7, 38 (1935). (3) Dubsky, J. V., and Trtilek, J., Mikrochemie, 15, 95 (1934). (4) Kolthoff. I. M., and Sandell. E. B.. “Textbook of Quantitative Inorganic Analysis”, 1st ed., pp. 454, 544, New %ark, Macmillan Co., 1936.
McCleary, H. R., and Hammett, L. P., J . Am. C h m . SOC.,63, 2254 (1941).
Milas, N. A., Ibid.,53,221 (1931). Roberts, I., IND. ENQ.C H E M ANAL. ., ED.,8, 365 (1936). Saifer, A., and Hughes, J., J . Biol. Chem., 118, 241 (1937): 121 801 (1937).
Analysis of Divinyl Ether in Blood WILLIAM L. RUIGH’ University of Pennsylvania, and Merck & Co., Inc., Rahway, N. J.
T
HE prediction of Leake and Chen (10) that the unsat-
urated ethers might have valuable anesthetic properties led to the preparation of divinyl ether by Ruigh and Major (19). It has recently been estimated that the number of patients receiving Vinethene anesthesia now exceeds a quarter of a million (13). I n this paper is described the method used for the determination of divinyl ether in the blood of anesthetized dogs and man. Some of the results obtained have already been published in papers (8, 17, 18, 19) which include both experimental and clinical studies of divinyl ether. Root has also used the method described for ethyl ether determinations in dogs (12). A preliminary method employed in determining blood concentrations depended on the initial hydrolysis of the divinyl ether in the blood sample to acetaldehyde by strong mineral acids, followed by precipitation of the protein by the FolinWu tungstate reagents, distillation of the aldehyde, and its titration by the method of Neuberg and Gottschalk (16). In this way it was found that in a dog the concentration of divinyl ether in the blood during light surgical anesthesia was 29 mg. per 100 cc., while at the point of respiratory failure it was 74 mg. per 100 cc. Because of rather aide variations in the check analyses, its time-consuming technique, and the fact that a t these anesthetic concentrations a correction factor of 25 per cent had to be added, the method was abandoned. The problem of satisfactorily determining the concentration of divinyl ether in the blood of anesthetized animals was finally solved by the development and modification of the iodine pentoxide method based on the reaction discovered by Ditte (2’) and first applied to the analysis of volatile organic compounds by Henderson and Haggard in the case of ethyl iodide (6-9). Haggard (4) later applied the method with I Present address, Squibb Institute for Medical Research, New Brunswick, N. J.
success to the analysis of ethyl ether in both water and blood. Since the completion of this work the method has been modified and adapted to the analysis of ethyl alcohol by Haggard and Greenberg (6) and to cyclopropane by Robbins (16). The original method as applied to ether consisted in aerating the sample of fluid, usually blood, and passing the stream of air carrying the volatile organic vapors over heated iodine pentoxide which oxidized the substance to carbon dioxide and water with the liberation of a stoichiometric amount of iodine. The iodine was absorbed in a solution of potassium iodide and titrated with thiosulfate in the usual manner. A simple calculation then gave the amount of volatile organic substance such as ethyl ether present in the blood or fluid being analyzed. Investigators in other laboratories have had great difficulty in handling the method (2] 6, 7, 11, 20). The main difficulties the author encountered and the means by which they were overcome were: Tubes filled with alternate layers of iodine pentoxide and glass wool prepared and “conditioned” according t o Haggard’s direc-
tions often failed to give reproducible results. Some tubes gave low and irregular results even after several days of conditioning. This was overcome by the use of a special pumice catalyst s u p port which offered a large surface and obvjated the “channeling” effect. Independently, Astapenya, Vapnik, and Zelkin (1) discovered the efficacy of a large surface in the use of iodine pentoxide for the analysis of carbon monoxide. With this type of filling, success was immediately obtained with each tube, whereas formerly tubes had to be abandoned even after a week of conditioning and numerous trial analyses. High and variable blanks were obtained. This was ascribed by Haggard mainly t o the quality of the iodine pentoxide. The author’s use of a tube of heated copper oxide removed any traces of organic impurities and carbon monoxide present in the air. This purifying train, together with the special contact mass, eliminated completely the necessity for a blank correction. Variations in the rate of air flow and very rapid rates of flow gave irregular results. The mechanical design of the apparatus
January 15, 1942
ANALYTICAL EDITION
33
obviated air pockets and a measured m o u n t of air at a definite slow rate was found necessary to obtain consistent results. The general method is widely applicable to the analysis of volatile organic compounds in body fluids. The more recent work of Haggard and Greenberg (6) on alcohol and of Robbins (16) on cyclopropane should be consulted if the method is to he adapted to the analysis of other organic compounds. Both modifications are more rapid than the author's and have about the same order of accuracy but employ very much higher rates of air flow. The limiting factor in his modification is the tendency of the blood sample to froth while air is being bubbled through it. Inthealcoholmethod theevaporation of a 1-cc. blood sample takes about 10 minutes. The 10-cc. samples required with divinyl ether would take proportionately longer. With the gas, cyclopropane, Robbins merely passed a rapid stream of air over the surface of the sample. Attention should be called to the discovery by Haggard and Greenberg (6) that in the case of ethyl alcohol oxidation is incomplete and a titration for hydrogen iodide as well as iodine must be made. Robbins (16) found that cyclopropane gave a stoichiometric amount of iodine corresponding to complete oxidation. Although the author has no definite experimental evidence, i t seems probable that the ratio of iodine to hydrogen iodide formed and hence the completeness of the oxidation to iodine is due to rate of air flow. surface and nature of iodine pentoxide catalyst mass, and nature of the organic material being oxidized. It is possible that the main reason for an average recovery of only 95 per cent in the author's method with both ethyl and divinyl ethen is the formation of some hydrogen iodide. The analytical results, however, are reliable and consistent when his procedure is employed. ~
Description of Apparatus The apparatus is shown in Figure 1. Outdoor air is led t o the ~~
~~~
~
~~~~
FIQ-
1. APPARATUS FOR DETERMINATION OF D I J ~ N Y ETEER L A. B. C. D. E. F.
C O P D ~oxide T tube and furnaoe Bubble counter Blood *erator Potasaium hydroxide trap Iodine pentoxide tube furnace Iodine absorber
bottom of the furnace is another No. 7 male ground-glass joint. The 8-mm. glass tube leading out of the furnace is wound with heavy copper wire which serves to conduct heat down the tube and thus prevent the deposition of iodine at the outlet of the
....
tricdly by a 110-volt current passed through 975 cm. of No. 20 pumice is then treated'with aqua regia for 24 hours, thoroughly B. and S. Nichrome wire (0.65 ohm per foot) which is wound waBhed, and ignited in a porcelain crucible for an hour a t red over B layer of asbestos paper. This winding is covered with heat. msguesia steam-pipe insulation. An exkrnd resistance is adForty grams of iodine pentoxide (iodic anhydride Merck) are iusted to keeu the CODDW oxide at 8. dull red heat. The connw ~~~~. --rr-dissolved in 35 cc. of hot water and the solution'is gradually oxide tube is'followedby a huhhle counter ooutaining a 30 per poured with stirrina onto 40 grams of the aranular pumice in a cent solution of potassium hydroxide.
.
~~~
~~~~
~
~
~
_I
&t t&ee-wav stonchck bv a short rubher connector for convenience in introdurihg the sample. By means of two three-way stopcocks the air flow can either he passed through the aerator durin the analysis or by-passed while sweeping the apparatus. F o l k i n g the aerator and connected t o it by means of the ground-glass joint is a U-trap. The arms of the U, 8 mm. in internal diameter, terminate in three bulblets of 5 cc. each and are 6Ued with pellets of potassium hydroxide. The bulblets, constricted at the bottom, are connected by a IO-cc. bulb which formed the bottom of the U and served to hold any liquefied caustic solution. Care should he taken to eliminate here and throughout the apparatus any "dead spaces" which might act as pockets when sweepingthe apparatus. The iodine pentoxide tubes used in this work were originally of the U form described by Haggard and heated in 8. Crisco bath. With continued use, however, the oil gave OKsuch objectionable fumes that an electrically heated furnace was made from a 30-cm. length of 5-cm. (2-inch) iron pipe wound with 9.6 meters (32 feet) of No. 20 B. and S. Nichrome wire on a double layer of asbestos paper (see also Haggard and Greenberg, 6). The furnace is then insulated with wrappings of asbestos paper softened with a sodium silicate solution. An external resistance serves to regulate the temperature. The reaction tube is connected with 2-mm. capillary tubing to the ground-glass joint of the potassium hydroxide Ptuhe. The reaction tube, 20 cm. long and 20 mm. in diameter, is filled with a 15-cm. length of iodine pentoxide-pumice held in place with two plugs of glass wool. Projecting at the
nated u a n u l ~ sare ready for the reaction tube. Ocoasi~&dl~. lumps ire formrd if t1.c Ptirrinc I Snot sufficiently vigorwr. 'I'L; rnatwinl murt tlirn bc rrworkd. TIS rntiir of ioilrne pentoxide to pumice IS not critical and Iwg+ dcprnA on the porosity of r l i ~ Ditniicc. (:ood tubes h . t w bem mud
