the range being from about m/e 206 to about rnle 520. The parent peak with the highest intensity occurred a t rnle 274, thus indicating the average molecular weight of this fraction to be about 7 carbon numbers less than that of cut 1. The -18 mass 2 series (phenanthreneslanthracenes) was prominent with the start of the series at mle 206. Phenylnaphthalene types were again apparent in lesser concentration than in cut 1. 3) Cut 3 (sulfide fraction). Cyclic sulfide fragments were in abundance in this fraction at m/e 101, 115, 129, 143, 155, 157, etc; the fragment of highest intensity was at rnle 183, the bicyclic sulfide series. The -18 mass 2 series (phenanthrenes/anthracenes) at rnle 206, 220, and 234 are prominent indicating some carryover of hydrocarbon material to this predominantly sulfide extract. The parent mass 2 series distributions were indicative of cyclic sulfide types, although some nitrogen and oxygen types may also be likely. These trends in the mass spectral data suggest that the chromatographic procedure functions well for this material. Sulfide types are apparently concentrated, and the hydrocarbon material is left essentially free of the sulfide compounds.
LITERATURE CITED (1) H. T. Rall, C. J. Thompson, H. J. Coleman, and R. L. Hopkins, U.S. Bur. Mines Bull. 659, (1972). (2) E. E. Reid, “Organic Chemistry of Bivalent Sulfur,” Vol. 11, Chemical Publishing Co., New York, NY, 1960, p 47. (3) R . S. Drago. G. C. Vogel, and T. E. Needham. J. Am. Chem. Soc.,93, 6014(1971).
(4) J. P. Sheridan, D. E. Martire, and Y. 6.Tewari, J. Am. Chem. Soc., 94, 3294 (1972). (5) R. G. Pearson, J. Chem. Educ., 45, 581 (1968). (6) R. G. Pearson, J. Chem. Educ., 45, 643 (1968). (7) V. G. Benkovskii, V. S. Nikitina, N. K. Lyapina, R . A. Rashitova, and T. S. Nikitina, Neftekhimiya, 12, 271 (1972); Petrol. Chem.: USSR. 12, 54 (1972). (8) W. L. Orr, Anal. Chem., 39, 1163 (1967). (9) F. Helfferich,J. Am. Chem. Soc., 84, 3237 (1962). (10) C. M. de Hernandez and H. F. Walton, Anal. Chem., 44, 890 (1972). (11) L.R. Snyder, Anal. Chem., 41,314(1969). (12) N. Ishibashi, S. Kamata, and M. Matsuura, Kogyo Kagaku Zasshi, 70, 1036 (1967); Chem Abstr., 68, 16437n (1968). (13) D. E. Hirsch, J. E. Dooley, H. J. Coleman, and C. J. Thompson, “Separation and Characterization Studies for a 370 to 535 OC Distillate of Wilmington, Calif. Crude Oil,” U.S. Bur. Mines Rept. lnvest., 7893, Bartlesville, OK, 1974. (14) W. A. Aue, C. R. Hastings, and S. Kapila, J. Chromatogr., 77, 299 (1973). (15) L. J. Andrews. ChemRev., 54, 713 (1954). (16) L. J. Andrews and R . M. Keefer, J. Am. Chem. Soc., 71, 3644 (1949). (17) L. J. Andrews and R. M. Keefer. J. Am. Chem. Soc., 72, 5034 (1950). (18) G. C. Pierotti. C. H. Deal, and E. L.Derr. lnd. fng. Chem., 51, 95 (1959). (19) D. E. Hirsch, R. L. Hopkins. H. J. Coleman, F. 0.Cotton, and C. J. Thompson, Anal. Chem., 44,915 (1972).
RECEIVEDfor review, November 7, 1974. Accepted, January 6, 1975. Reference to specific brand names is made for identification only and does not imply endorsement by the Bureau of Mines. The investigation performed is part of the work of American Petroleum Institute Research Project 60 on “Characterization of Heavy Ends of Petroleum,” which the Bureau of Mines has conducted a t the Bartlesville (OK) and Laramie (WY) Energy Research Centers.
Detection and Estimation of Bis(ch1oromethyl)ether in Air by Gas Chromatography-High Resolution Mass Spectrometry Kenneth P. Evans, Alan Mathias,’ Norman Mellor, Raymond Silvester, and Albert E. Williams Imperial Chemical Industries Limited, Organics Division, Blackley, Manchester, England
There is mounting evidence that bis(ch1oromethyi)ether (BCME), which is reported to form spontaneously from the two common materials formaldehyde and HCI, is a carcinogen. A method is presented, which uses adsorption and then combined gas chromatography-high resolution mass spectrometry to detect the presence of BCME In air reliably and with a very high degree of specificity. The method involves “mass fragmentographic” monitoring of the ion m/e 78.9950 (C2H40CI+) from BCME and is shown to be applicable down to levels of 0.1 ppb v/v BCME on a 1-1. air sample or 0.01 ppb v/v BCME if a 10-1. air sample is taken.
Considerable concern has been generated in many branches of the chemical industry following two announcements. The first concerned the mounting evidence on the carcinogenicity of bis(chloromethyl)ether, ClCH20CH2C1, when present in air even a t very low levels (1-4). The second concerned the report that bis(chloromethy1)ether (BCME) could be formed spontaneously in air or solution from the two very common industrial materials, hydrochloric acid and formaldehyde ( 5 ) .In general terms, it was reported that HC1 and formaldehyde, a t their threshold limit values in air of 5 ppm and 2 ppm, respectively, could yield Author t o whom all correspondence should be addressed.
BCME a t a level of a few parts in lo9 (ppb vlv). An immediate need for analytical methods for the reliable identification and quantitative determination of BCME at these levels arose, and details of two such methods have been reported already (6, 7 ) .Although subsequent results have indicated that the formation of BCME from HC1 and formaldehyde does not take place quite so readily as first proposed (8, 9 ) , the need for reliable methods for the determination of BCME in the ppb range in laboratory and manufacturing plant atmospheres, and even inside manufacturing processes, remains real. In order to reach the low levels involved, all methods rely upon a pre-concentration stage in which a known volume of air is drawn through an adsorption tube. Both Poropak Q (6, 8) and Chemosorb 101 (7, 9 ) , have been shown to be suitable packing materials which can adsorb, and subsequently desorb, BCME quantitatively a t the levels concerned. As a rough screening method, examination of the adsorbed material by gas chromatography can be used. The adsorption tube can be fitted into the head of a slightly modified GC unit, the collected organic material desorbed, separated, and the resulting chromatogram examined over the BCME retention time region, previously established using standard BCME solutions. Failure to observe any BCME peak can set an upper limit on any BCME in the sampled atmosphere. However, observation of a peak in the BCME region does not provide conclusive proof of the ANALYTICAL CHEMISTRY, VOL. 47, NO. 6, MAY 1975
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presence of BCME. Also, in sampling many laboratory or plant atmospheres, the resulting chromatogram is likely to be complex, and interference over the BCME retention time region, to a degree which makes BCME determination impossible at the levels concerned, will be common place. T o provide greater specificity and reduce the possibility of interference by other components, a double GC system can be used where the effluent in the BCME region from the first column is gated on to a second differently packed column (8). Alternatively, the adsorbed organic material can be examined directly by mass spectrometry. Collier (6) has given details of a method in which the collected organic material is desorbed into the reservoir of the mass spectrometer heated inlet system and then examined at high resolution for the presence of the ion rnle 78.9950 (C2H40Cl+) which is the most intense ion in the BCME mass spectrum. The method was shown to be capable of determining BCME a t levels of 1 ppb vlv in the original sampled atmosphere. The method has been criticized ( 7 ) since there will be interference if other species are present which yield the ion concerned, for example, chloromethyl methyl ether. In our experience, adsorption and regeneration effects, and possible decomposition of BCME in the reservoir and its associated valves, can be a problem, unless extreme care is taken in this method. Greater specificity and high sensitivity of detection can be achieved using gas chromatography-mass spectrometry (GC-MS). Shadoff et al. ( 7 ) have reported such a method. After the particular atmosphere has been sampled using an adsorption tube, the collected organic species are subjected to gas chromatographic separation, and the mass spectrometer is set to monitor mle 79 and its chlorine isotope peak mle 81 simultaneously. Simultaneous detection of two peaks is necessary since the probability of a species eluting with a retention time close to that of BCME and also giving an ion of the relatively common nominal mle 79 is unacceptably high. Positive detection of BCME is dependent upon there being simultaneous response of mle 79 and mle 81, in the 3:l ratio needed for a chlorine isotope pair, at the retention time for BCME. Again, the method is reported to be quantitative down to BCME levels of 1 ppb v/v in the sampled atmosphere. Uncertainties in the above method will result if a chlorine-containing species giving rnle 79 elutes with a retention time similar to BCME or if any component giving mle 79 or mle 81 elutes with a retention time close to that of BCME, so that the ratio of rnle 79 to mle 81 deviates markedly from the expected 3:1, leaving one in doubt whether BCME is present or not. In our experience in monitoring plant atmosphere and reaction headspaces where numerous species are adsorbed, it is the latter situation which is the more troublesome. For some time now, we have obtained the greater specificity required by monitoring the base ion of BCME, mle 78.9950 (CZH40C1+),exclusively at high mass spectral resolution during the chromatogram. This gives a highly specific, highly sensitive method of BCME determination and details are presented below. The fact that greater specificity could be achieved in this way was suggested independently by Shadoff et al. ( 7 ) .The method can be extended, in principle, to the determination of other low concentration species in air.
EXPERIMENTAL Sampling Tubes. These are of two types depending upon the volume of air to be sampled. For volumes up to 1 l., sampling tubes are made from 10-cm lengths of 3.2-mm o.d., 2.5-mm i.d. Pyrex 822
ANALYTICAL CHEMISTRY, VOL. 47, NO. 6, M A Y 1975
glass tubing, specially selected to give a good fit with the modified GC head (see below). A 5-cm length from one end of the tube is packed with 60-80 mesh Poropak Q, retained with quartz wool plugs. Prior to packing, the Poropak Q is washed with ethylene dichloride by Soxhlet extraction overnight, and then conditioned by heating in a stream of nitrogen for 2 hr. For sampling larger volumes, up to 10 l., larger sampling tubes are required since the breakthrough volume of the small tubes above would be exceeded. These are made from 15-cm lengths of 6.4-mm o.d., 5.0-mm i.d. Pyrex glass tubing, one end of which is drawn out to about 2.5-mm 0.d. Poropak Q retained by quartz wool plugs is used for packing. When these larger tubes have been used, the adsorbed organic material must be transferred to one of the smaller tubes, mentioned above, which fit the modified head of the GC unit. T o do this, the constricted end of the larger tube is connected to a freshly packed smaller tube with a short length of silicone rubber tubing. A small desorption heater is placed round the larger tube, which is then heated to 200 OC. Pure nitrogen is passed through both coupled tubes a t a rate of 100 ml/min, desorbing any collected organic material from the larger tube for readsorption in the smaller tube. Tests using measured amounts of standard BCME solutions in monochlorobenzene showed that 600 ml of NPeffected quantitative transfer of BCME from the larger to small tube under these conditions. Sampling Method. Prior to use, the packed sample tubes are calibrated using the rotary suction pump which will be used for the actual sampling and a flow meter attached temporarily to the inlet side of the sampling tubes. Flow rates of 250 ml/min were typical for both the larger and smaller sample tube when coupled to the common types of small rotary pumps. Samples are then taken onsite by drawing air through the sample tube for a time appropriate for the requred sample volume. The sample tubes are then capped and taken for GC-MS examination. Previous workers (6-9) have established that the abstraction of BCME is quantitative under these conditions, as is the subsequent regeneration of BCME, and that the collected BCME samples are stable for a period of days. We concur with these findings, with the proviso that results may be suspect if the sampled atmosphere is so wet that the Poropak Q is obviously damp after sampling. This is most unlikely to occur in sampling laboratory or plant atmospheres, but would occur in sampling manufacturing process headspaces, for example. Gas Chromatography. A Pye 104 gas chromatograph is used. This is an integral part of our AEI MS.30 mass spectrometer system. Columns are made from 9 ft of 4-mm i.d. glass tubing packed with 30% poly(ethy1ene glycol) adipate on 100-120 mesh acid washed Celite, conditioned initially by heating a t 190 “C in a stream of nitrogen overnight. The normal GC insertion head is modified to enable the small sample tubes discussed above to be inserted directly into the GC column to a depth of 8 cm. The standard Pye 104 Marinite plug is cut back by 3/4 inch so that the Poropak adsorbent is in the top of the GC oven under these conditions. When inserted, the ‘k-inch 0.d. sample tube is locked to the %-inch 0.d. GC column end with a gas tight Y4-?4-in. Drallim “captive seal” brass coupling. About 2 cm of the sample tube project from the column head, so that the carrier gas flow can be connected using a small length of silicone rubber tubing. On insertion, the sample tube rapidly reaches the GC oven temperature, desorption of the collected organic species begins, and the chromogram starts with the simultaneous recoupling of the carrier gas flow. The GC conditions used are: temperature 150 ‘C; helium flow rate 40 ml/ min; approximate BCME retention time, 6.5 minutes. Mass Spectrometric Conditions. The mass spectrometer must first be set up to observe m / e 79. A convenient way to do this is to make an initial examination of Fluothane, CF&HClBr, introduced via the AGHIS unit with the spectrometer operating at “low resolution” (nominal R.P. 1000). The large m / e 69 peak is recognized easily and the 79Br peak is then centered on the oscilloscope by direct counting. The resolving power is increased to “medium” (RP 3800 on our system) and the scan narrowed. As a confirmatory check that the 79Br peak has been selected properly a t R P 3800, an accurate mass check of this peak against the *IBr isotope peak is made. The Fluothane is then pumped from the system. The AEI MS.30 GC-mass spectrometer system is equipped with a silicone membrane type separator in the GC-MS interface. For BCME, the optimum operating temperature of this interface was 70 OC. The mass spectrometer is set as follows: resolving power, “medium” (3800 on our system); filament setting 3 (100 WAtrap current); multiplier setting 6 (Le., high gain). Other parameters were set as appropriate for the particular operations discussed below.
(a) D\ 1 C H 790458
c
\
'
:
^
I
Typical appearance of the m/e 79 region of the mass spectrum at resolving power 3800. Position of the ion m/e 78.9950 (CIC2H40+)from BCME is shown'as a dotted band Figure 1.
d
To help improve the signal-to-noise characteristics for some steps, a simple RC variable filter network was added between the spectrometer and the recorder. This could be switched between the signal output and the total ion current detector output as appropriate. Calibration. Previous workers (6, 8) have shown that the adsorption of BCME onto the Poropak Q filled tubes, and its subsequent regeneration by heating in a carrier gas stream, as discussed above, proceeds quantitatively. Our own results support this. After regeneration, into the GC-MS system, our methods depend upon the detection of the specific ion m/e 78.9950 (CZHdOCl+) a t the correct retention time for BCME. To provide a continuing check on this retention time and also to make quantitative estimates possible, we adopt the procedure of examining BCME standards both before and immediately after the examination of an unknown sample, under identical instrument conditions. Standards are prepared by injecting a known amount of a standard BCME solution in monochlorobenzene onto a freshly prepared Poropak adsorption tube. A convenient procedure, used to examine a standard immediately after an unknown, is to momentarily interrupt the carrier gas flow after the chromatogram of an unknown sample is completed and to inject the BCME standard onto the same tube and repeat the examination procedure. Experimental conditions between the standard and unknown sample thus become as close as possible. The strength of standard is chosen as appropriate. As a guide, 1 ~1 of an 0.001% solution of BCME in MCB contains the same amount of BCME as 1 1. of a sampled atmosphere containing 2 ppb v/v of BCME.
RESULTS AND DISCUSSION The necessary high specificity of detection for BCME is achieved by monitoring continuously the ion C2H40Cl+, mle 78.9950, while the species collected on a Poropak Q adsorption tube are chromatographed. Thus, for positive identification, stringent GC and MS conditions must be satisfied simultaneously. Since in this mode the mass speetrometer is operating under single peak monitoring conditions, the method is particularly sensitive. The typical appearance of the nominal mle 79 region at RP 3800, as shown by our MS.30 mass spectrometer, is given diagrammatically in Figure 1. At the instrument sensitivity concerned, four background peaks will be observed. The size of the hydrocarbon background peaks mle 79.0458-79.0547 varies considerably depending upon the operating state of cleanliness of the Spectrometer. The particular peaks also vary in intensity, and other nominal mle 79 peaks appear and fall away, as the chromatogram proceeds and different components elute. These effects underline the dangers of relying solely upon the observation of nominal mle 79 a t low resolution for BCME detection. Also shown in Figure 1 is the position at which the peak due to BCME will appear at the specific time during the chromatogram if RCME is present. The initial method of BCME detection that we used involved the repetitive scan-
i
6
Retention time imins)
Appearance of BCME peak, m/e 78.9950 (CIC2H40+) using combined gas chromatographic-high resolution mass spectro-
Figure 2.
metric method of detection ( a ) BCME equivalent to 2.5 ppb v/v in 14. sample, "dynamic" method. ( b ) BCME equivalent to 2.5 ppb v/v in 1-1. sample, "static" method. (c) BCME equivalent to 5.0 ppb v/v in a 1-1. sample, "dynamic" method. (d)BCME equivalent to 5.0 ppb v/v in a 1-1.sample, "static" method
ning (1 scanlsec) of the pattern as shown in Figure 1 throughout the chromatogram and observing the rise of the mle 78.9950 peak. The maximum peak height and its time of arrival were noted. The results were made quantitative and a continuous check was kept on the accurate BCME retention time by the examination of BCME standards before and after a sample. This method has the drawback that no permanent records are available. This is rectified easily by outputting the signal to the UV recorder (chart speed 2 cmlsec). A repetitive histogram of the oscilloscope display is now obtained in which the spike due to BCME can be observed to rise and fall away a t the specific time if BCME is present. Using this method, levels of BCME down to 1 ppb in 1 1. of sampled atmosphere could be detected and quantified reliably. The method above was improved and greater sensitivity of detection achieved when tests showed that the overall stability of the MS.30 mass spectrometer was such that it is possible to set the system to monitor mle 78.9950 specifically and reliably at R P 3800 for periods of time long enough to examine a BCME sample and its associated references. The operational procedure is modified as follows. Using the methods already described, the oscilloscope presentation shown in Figure 1 is displayed. A BCME standard is then examined and as the BCME is detected, the scope presentation is widened so that the rnle 78.9950 peak virtually fills the scope screen, with the peak centroid accurately positioned at oscilloscope center. Two methods may now be used. Static Method. Here the oscilloscope scan is switched off and the spectrometer static output is transferred to the UV recorder or the pen recorder normally used for TIC detection. A BCME sample and its associated references are then examined. This method is the most sensitive for BCME detection, but one relies entirely upon the stability of the spectrometer to hold mle 78.9950. Dynamic Method. Here the oscilloscope is left scanning and, after the BCME standard used to center the expanded BCME peak has eluted, the oscilloscope will show a flat base line with a slight rise to the high mass side. This rise is ANALYTICAL CHEMISTRY, VOL. 47, NO. 6, MAY 1975
823
C
i
1
7
6
20
0
BCME concentration ppb/lL
sample
Flgure 4. Plots of areas of BCME peaks observed using combined gas .chromatographic-high resolution mass spectrometric method of detection vs. BCME concentration, expressed in terms of ppb v/v In a 1-1. air sample, for a series of samples examined under identical instrumental conditions; (0)”static” method, (A)“dynamic” method
Retention time (mins)
Figure 3. BCME peak, m/e 78.9950 (CIC2H40+)using combined gas chromatographic-high resolution mass spectrometric method of detection from BCME equivalent to 0.16 ppb v/v in a 1-1. air sample, (a) “static” method, (6) “dynamic” method
caused by the skirt of the background peak m/e 79.0047 due to C4H3Si+, which is always observed in our system at these sensitivities. The oscilloscope is left running at 1 s e d scan throughout the chromatogram of the subsequent BCME sample and reference. The UV recorder or pen recorder will follow the signal reasonably with only slight sensitivity loss compared with the Static Method. The Dynamic Method has the advantage that the small C4H3Si+ skirt is displayed as a standing signal maintained a t constant amplitude, provided there is no drift in the MS.30 mass scale, thus giving valuable assurance that the system remains accurately centered on mle 78.9950. When BCME elutes in experimental or reference samples, its peak will sit on top of this constant background. Examples of the presentations discussed above are shown in Figure 2 . This shows the appearance of the BCME peak m/e 78.9950 at the BCME retention time of 6.5 minutes for samples equivalent to 2.5 ppb v/v BCME in a 1-1. air sample, ( a ) and ( b ) ,and 5.0 ppb v/v BCME in a 1-1. air sample, ( c ) and ( d ) . The traces were obtained under the same instrumental conditions and hence the slightly lower sensitivity of the “dynamic” method, ( a ) and ( c ) , compared to the “static” method, ( b ) and ( d ) ,can be noted. However, the useful standing signal due to the C4HsSi+ skirt can be seen in the traces from the “dynamic” method, ( a ) and ( c ) . Figure 3 shows responses using the “static” ( a ) and “dynamic” ( b ) methods from a BCME sample equivalent to 0.16 ppb v/v of BCME in a 1-1. air sample. Clearly, at this level of BCME, the detection limit of the method is being approached and, on this basis, a lower limit of detection for BCME for the combined GC-high resolution mass spectrometric method is placed a t 0.1 ppb v/v of BCME in a 1-1. air sample or 0.01 ppb v/v when a 10-1. air sample is taken.
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ANALYTICAL CHEMISTRY, VOL. 47, NO. 6, M A Y 1975
Figure 4 shows plots of the areas of the BCME peaks observed under “dynamic” and “static” conditions vs. BCME concentration for a series of samples examined under the same experimental conditions. The plots demonstrate the direct proportionality of area vs. BCME concentration over the concentration region of interest, provided experimental conditions remain unaltered. Using a GC-MS system, absolute reproducibility of the complete system response cannot be guaranteed from day to day. Thus a single calibration graph, as shown in Figure 4, cannot be used. However, the plot does provide confidence in the experimental method that is used in practice for quantitative measurementsnamely, to compare directly the peak areas observed from the unknown with reference BCME samples examined immediately before and after the unknown without any change in system operating conditions. The GC-high resolution mass spectrometric method has been used successfully by us for some time on numerous samples taken from various manufacturing plant atmospheres and from reaction headspaces in laboratory and manufacturing processes.
LITERATURE CITED (1) 6.L. Van Duuren. B. M. Goldschrnidt, L. Langseth. et al., Arch. Environ. Health, 18, 472 (1968). (2) 6.L. Van Duuren. A. Sinak, 6. M. Goldschrnidt, et al., J. Nat. Cancer Inst., 43, 481 (1969). (3) S. Laskin, M. Kuschner. R. T. Drew, et at., Arch. Environ. Health, 23, 135 (197 1). (4) 6.K. J. Leong, H. N. Macfarland. and W. H. Reese, Arch. Environ. Health, 22,663 (197i). (5) Chem. Eng. News, Jan. 8, 1973, p 13. (6) L. Collier, Environ. Sci. Techno/., 6, 930 (1972). (7) L. A. Shadoff, G. J. Kallos, and J. S. Woods, Anal. Chem., 45, 2341 (1973). (8) L. S. Frankel, K. S. McCallurn, and L. Collier, Environ. Sci. Techno/., 8, 356 (1974). (9) G. J. Kallos and R . A. Solomon, Am. ind. Hygiene Assoc. J., Nov. 1973, p 469.
RECEIVED for review August 19, 1974. Accepted January 16, 1975.
