impregnated asbestos) instead of K2C03. However, under some conditions, there was appreciable reaction a t room t e m p e r a t u r e with t h e "Ascarite" t o release fluoroform, resulting in low values. W i t h K2C03, no significant reaction occurs until heated. T h e only difficulty t h a t has occurred with t h e procedure is a n occasional low result d u e t o failure t o have t h e Beckm a n cell system properly evacuated. T h i s can come a b o u t through leaks a t t h e lha-inch "Swagelok" fittings, or, more commonly, from a plugged needle (from coring t h e s e p t u m )
during t h e evacuation step. Use of a H u b e r point needle (22-gauge) helps. W h e n t h e 5 ml of nitrogen is a d d e d after heating t h e tube, it will be immediately a p p a r e n t if a good vacuum was obtained a n d kept. T h e greased syringe should pull down t o 3 or 4 m l if a good vacuum was present. If i t does not, t h a t r u n should be discarded. Use of t h e G r u b b Parsons cell avoids this type of problem.
RECEIVEDfor review J a n u a r y 7, 1974. Accepted M a y 9, 1974.
Determination of Acetaldehyde in Glacial Acetic Acid by Gas Chromatography Harold J. Rhodes, David W. Bode, and Martin 1. Blake College of Pharmacy, University of Illinois at the Medical Center, Chicago, 111. 606 72
T h e presence of acetaldehyde as a contaminant in glacial acetic acid m a y introduce a significant error in t h e analysis of compounds containing a primary a m i n e group when perchloric acid in acetic acid is used as t h e t i t r a n t . As a n example, in t h e USP assay procedure ( I ) for procainamide hydrochloride, t h e presence of 50 p p m or more of acetaldehyde in t h e glacial acetic acid used as t h e titration solvent introduced a sizeable error in t h e per cent recovery of t h e salt because of Schiff base formation. A simple gas-liquid chromatographic procedure was developed t o monitor t h e glacial acetic acid for acetaldehyde content, particularly where t h e solvent is used in t h e perchloric acid titration of bases a n d certain salts. EXPERIMENTAL Apparatus. A Research Specialties, Model 60-10, gas chromatograph equipped with a flame ionization detector and a Westronics, Inc., strip chart recorder, Model LSllA/MA/DVGH was employed in this study. 'The coiled stainless steel column (183 cm long X 0.3-cm i.d.) was packed with Chromosorb 101 (60-80 mesh). The initial conditioning of the new column was conducted at a temperature of 200 "C for 24 hours. The gas chromatograph operating conditions were as follows: the nitrogen carrier gas flow rate was 63 ml/min under a column head pressure of 32 psig, the hydrogen flow rate was 58 ml/min, and the air flow rate was 280 mlimin. The injection port, column, and detector temperatures were 160 O C , 140 "C, and 160 "C, respectively. The electrometer current sensitivity was 1.3 X lo-'* amperes full-scale in the most sensitive setting. Signals were recorded at an attenuation factor of X 30. A Hamilton syringe (10-pI) was used for injecting the samples of 4-pl volume. Reagents. Acetaldehyde was freshly-distilled and cooled to 10 "C. Distilled water was used to prepare solutions of acetaldehyde of varying known concentrations. The samples of reagent grade glacial acetic acid used for the determination of acetaldehyde content were obtained from J. T. Baker Chemical Company, Fisher Scientific Company, Eastman Kodak Company, and E. I. du Pont de Nemours and Company, Inc. Procedure. A calibration curve was prepared by injecting 4 pl of aqueous solutions of acetaldehyde of known concentrations in the range of 1 to 20 ppm. The concentration of acetaldehyde present in each of'the known samples was determined by calculating the area (1)
"The United States Pharmacopeia." 18th rev., Mack Printing Go., Easton, Pa., 1970, p 542.
1584
Table I. A c e t a l d e h y d e C o n t e n t of Glacial A c e t i c A c i d O b t a i n e d f r o m C o m m e r c i a l Sources Source
Acetaldehyde content, wm''
A B
5.5
C
2.4 2.4
D
2.8
Average of three determinations.
under each of the respective curves obtained in the chromatograms. The area under the curve was calculated by multiplying the height of the peak times the width of the peak at one-half height. The calibration curve was prepared by plotting the concentration in ppm LIS the area under the curve. A straight line relationship was obtained. The concentration of acetaldehyde in 4 pl of the glacial acetic acid test sample was then determined by calculating the area under the curve obtained for the acetaldehyde content and relating it to the calibration curve values. RESULTS A N D DISCUSSION All samples of glacial acetic acid taken for analysis showed two peaks in t h e chromatogram; t h e first peak represented acetaldehyde (retention time, 50 seconds) a n d t h e second was t h e acetic acid peak (retention time, 115 seconds). No other peaks were found which could be confused with or could interfere with t h e acetaldehyde peak. T h e acetaldehyde content in t h e glacial acetic acid obtained from four commercial sources was determined by GLC a n d t h e d a t a a r e reported in T a b l e I. T h e e x t e n t of acetaldehyde contamination in these instances was not sufficiently great to cause a n y serious problem in t h e assay of procainamide hydrochloride. However, in other situations, acetaldehyde contamination could represent a more serious problem. I t is therefore recommended t h a t specification limits be imposed on t h e acetaldehyde content of commercial glacial acetic acid. T h e gas chromatographic analysis procedure presented here is simple. accurate, a n d provides for a routine monitoring of glacial acetic acid used for the nonaqueous titration of drugs a n d dosage forms. RECEIVED for review March 21, 1974. Accepted M a y 16,
1974.
ANALYTICAL CHEMISTRY, VOL. 46, NO. 11, SEPTEMBER 1974
