Revision 1.0
September 1986

METHOD TO-7

METHOD FOR THE DETERMINATION OF N-NITROSODIMETHYLAMINE
IN AMBIENT AIR USING GAS CHROMATROGRAPHY

1. Scope

1.1	This document describes a method for determination of N-
nitrosodimethylamine (NDMA) in ambient air. Although the method,
as described, employs gas chromatography/mass spectrometry
(GC/MS), other detection systems are allowed.

1.2	Although additional documentation of the performance of this
method is required, a detection limit of better than 1 ug/m3 is
achievable using GC/MS (1,2). Alternate, selective GC detection
systems such as a thermal energy analyzer (2), a thermionic
nitrogen-selective detector (3), or a Hall Electrolytic
conductivity detector (4) may prove to more sensitive and
selective in some instances.

2. Applicable Documents

2.1	ASTM Standards

D1356 Definitions of Terms Related to Atmospheric Sampling and
Analysis (5)

2.2	Other Documents
Ambient air studies (1,2)

U.S. EPA Technical Assistance Document (6)

3. Summary of Method

3.1	Ambient air is drawn through a Thermosorb/N adsorbent cartridge at
a rate of approximately 2 L per minute for an appropriate period
of time. Breakthrough has been shown not to be a problem with
total sampling volumes of 300 L (i.e., 150 minutes at 2 L per
minute). The selection of Thermosorb/N absorbent over Tenax GC,
was due, in part, to recent laboratory studies indicating artifact
formation on Tenax from the presence of oxides of nitrogen in the
sample matrix.

3.2	In the laboratory, the cartridges are pre-eluted with 5 mL of
dichloromethane (in the same direction as sample flow) to remove
interferences. Residual dichloromethane is removed by purging the

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cartridges with air in the same direction. The cartridges are
then eluted, in the reverse direction, with 2 mL of acetone. This
eluate is collected in a screw-capped vial and refrigerated until
analysis.

3.3 NDMA is determined by GC/MS using a Carbowax 2 0M capillary column.
NDMA is quantified from the response of the m/e 74 molecular ion
using an external standard calibration method.

4.	Significance

4.1	Nitrosamines, including NDMA, are suspected human carcinogens.
These compounds may be present in ambient air as a result of
direct emission (e.g., from tire manufacturing) of from
atmospheric reactions between secondary or tertiary amines and
N0X.

4.2	Several papers (1,2,4) have been published describing analytical
approaches for NDMA determination. The purpose of this document
is to combine the attractive features of these methods into one
standardized method. At the present time, this method has not
been validated in its final form, and, therefore, one must use
caution when employing it for specific applications.

5.	Definitions

Definitions used in this document and in any user-prepared SOPs should
be consistent with ASTM D1356(5). All abbreviations and symbols are
defined within this document at the point of use.

6.	Interferences

Compounds having retention times similar to NDMA, and yielding
detectable m/e 74 ion fragments, may interfere in the method. The
inclusion of a pre-elution step in the sample desorption procedure
minimizes the number of interferences. Alternative GC columns and
conditions may be required to overcome interferences in unique
situations.

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7.	Apparatus

7.1	GC/MS System - capable of temperature-programmed, fused-silica
capillary column operation. Unit mass resolution or better to 300
amu. Capable of full scan and selected ion monitoring with a scan
rate of 0.8 second/scan or better.

7.2	Sampling system - capable of accurately and precisely sampling
100-2000 mL/minute of ambient air. (See Figure 1.) The dry test
meter may not be accurate at flows below 500 mL/minute; in such
cases it should be replaced by recorded flow readings at the
start, finish, and hourly during the collection. See Section 9.4.

7.3	Stopwatch.

7.4	Friction top metal can, e.g., one-gallon (paint can) - to hold
clean cartridges and samples.

7.5	Thermometer - to record ambient temperature.

7.6	Barometer (optional).

7.7	Glass syringe - 5 mL with Luer fitting.

7.8	Volumetric flasks - 2 mL, 10 ml, and 100 mL.

7.9	Glass syringe - 10 uL for GC injection.

8.	Reagents and Materials

8.1	Thermosorb/N - Available from Thermedics Inc., 47 0 Wildwood St.,
P.O. Box 2999, Woburn, Mass., 01888-1799, or equivalent.

8.2	Dichloromethane - Pesticide quality, or equivalent.

8.3	Helium - Ultrapure compressed gas (99.9999%) .

8.4	Perfluorotributylamine (FC-43) - for GC/MS calibration.

8.5	Chemical Standards - NDMA solutions. Available from various
chemical supply houses. Caution: NDMA is a suspected human
carcinogen. Handle in accordance with OSHA regulations.

8.6	Granular activated charcoal - for preventing contamination of
cartridges during storage.

8.7	Glass jar, 4oz- to hold cartridges.

8.8	Glass vial - 1 dram, with Teflon -lined screw cap.

8.9	Luer fittings - to connect cartridges to sampling system.

8.10	Acetone - Reagent grade.

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9. Sampling

9.1	Cartridges (Thermosorb/N) are purchased prepacked from Thermedics
Inc. These cartridges are 1.5 cm ID x 2 cm long polyethylene
tubes with Luer -type fittings on each end. The adsorbent is
held in place with 100-mesh stainless steel screens at each end.
The cartridges are used as received and are discarded after use.
At least one cartridge from each production lot should be used as
a blank to check for contamination. The cartridges are stored in
screw-capped glass jars (with Luer style caps), and placed m a
charcoal-containing metal can when not in use.

9.2	The sampling system may employ either a mass flow controller or a
dry test meter. (See Figure 1.) For purposes of discussion, the
following procedure assumes the use of a dry test meter.

9.3	Before sample collection, the entire assembly (including a "dummy"
sampling cartridge) is installed and the flow rate is checked at a
value near the desired rate. In general, flow rate of 100-2000
mL/minute should be employed. The flow rate should be adjusted so
that no more than 300 L of air is collected over the desired
sampling period. Generally, calibration is accomplished using a
soap bubble flow meter or calibrated wet test meter connected to
the flow exit, assuming the system is sealed. ASTM Method 3686
describes an appropriate calibration scheme not requiring a sealed
flow system downstream of the pump.

9.4	Ideally, a dry gas meter is included in the system to record total
flow. If a dry gas meter is not available, the operator must
measure and record the sampling flow rate at the beginning and end
of the sampling period to determine sample volume. If the
sampling period exceeds two hours, the flow rate should be
measured at intermediate points during the sampling period.
Ideally, a rotameter should be included to allow observation of
the flow rate without interruption of the sampling process.

9.5	To collect an air sample, a new Thermosorb/N cartridge is removed
from the glass jar and connected to the sampling system using a
Luer adapter fitting. The glass jar is sealed for later use.
The following parameters are recorded on the data sheet (see
Figure 2 for an example): date, sampling location, time, ambient
temperature, barometric pressure (if available), relative humidity
(if available), dry gas meter reading (if appropriate), flow rate,
rotameter setting, cartridge batch number, and dry gas meter and
pump identification numbers.

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9.6	The sampler is allowed to operate for the desired period, with
periodic recording of the variables listed above. The total flow
should not exceed 300 L.

9.7	At the end of the sampling period, the parameters listed in
Section 9.5 are recorded and the sample flow is stopped. If a dry
gas meter is not used, the flow rate must be checked at the end of
the sampling interval. If the flow rates at the beginning and end
of the sampling period differ by more than 15%, the sample should
be marked as suspect.

9.8	Immediately after sampling, the cartridge is removed from the
sampling system, capped, and placed back in the 4-oz glass jar.
The jar is then capped, sealed with Teflon tape, and placed m a
friction-top can containing 1-2 inches of granular charcoal. The
samples are stored in the can until analysis.

9.9	If a dry gas meter or equivalent total flow indicator is not used,
the average sample flow rate must be calculated according to the
following equation:

where

Qa =	average flow rate (mL/minute).

Qlr Q2,....Qn =	flow rates determined at beginning, end, and

immediate points during sampling.
N	=	number of points averaged.

9.10 The total flow is then calculated using the following equation:

v	(T2-Tl) x

m	1000

where

Vm =	total sample volume (L) at measured temperature

and pressure.

T2	=	stop time.

T-l =	start time.

¦T-l	=	sampling time (minutes) .

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9.11 The total volume (V3) at standard conditions, 25°C and 760 mm Hg,
is calculated from the following equation:

V = V X	- 298

760 273 +

where V3 =	total sample volume (L) at standard conditions

of 25°C and 760 mm Hg.

Vm =	total sample volume (L) at measured temperature

and pressure.

PA =	average barometric pressure (mm Hg).

tA =	average ambient temperature (°C) .

10. Sample Desorption

10.1	Samples are returned to the laboratory and prepared for analysis
within one week of collection.

10.2	Using a glass syringe, the samples are pre-eluted to remove
potential interferences by passing 5 mL of dichloromethane through
the cartridge, in the same direction as sample flow. This
operation should be conducted over approximately a 2-minute
period. Excess solvent is expelled by injecting 5 mL of air
through the cartridge, again using the glass syringe.

10.3	The NDMA is then desorbed passing 2 mL of acetone through the
cartridge, in the direction opposite to sample flow, using a glass
syringe. A flow rate of approximately 0.5 mL\minute is employed
and the eluate is collected in a 2-mL volumetric flask.

10.4	Desorption is halted once the volumetric flask is filled to the
mark. The sample is then transferred to a 1-dram vial having a
Teflon -lined screw cap and refrigerated until analysis. The vial
is wrapped with aluminum foil to prevent photolytic decomposition
of the NDMA.

11. GC/MS Analysis

Although a variety of GC detectors can be used for NDMA determination,
the following procedure assumes the use of GC/MS in the selected ion
monitoring (SIM) mode.

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11.1	Instrument Setup

11.1.1	Considerable variation in instrument configuration is
expected from one laboratory to another. Therefore,
each laboratory must be responsible for verifying that
its particular system yields satisfactory results.

The GC/MS system must be capable of accommodating a
fused-silica capillary column, which can be inserted
directly into the ion source. The system must be
capable of acquiring the processing data in the
selected ion monitoring mode.

11.1.2	Although alternative column systems can be used, a 0.2
mm I.D. x 50 m Carbowax 20M fused-silica column
(Hewlett-Packard Part No. 19091-60150, or equivalent)
is recommended. After installation, a helium carrier
gas flow of 2 mL per minute is established and the
column is conditioned at 250°C for 16 hours. The
injector and GC/MS transfer line temperatures should
also be set at 250°C.

11.1.3	The MS and data system are set up according to
manufacturer's specifications. Electron impact
ionization (70eV) should be employed. Once the entire
GC/MS system is set up, it is calibrated as described
in Section 11.2. The user should prepare a detailed
standard operating procedure (SOP) describing this
process for the particular instrument being used.

11.2	Instrument Calibration

11.2.1	Tuning and mass standardization of the MS system is

performed according to manufacturer's instructions and
relevant information from the user-prepared SOP.
Perfluorotributylamine should generally be employed
for this purpose. The material is introduced directly
into the ion source through a molecular leak. The
instrumental parameters (e.g., lens, voltages,
resolution, etc.) should be adjusted to give the
relative ion abundances shown in Table 1 as well as
acceptable resolution and peak shape. If these
approximate relative abundances cannot be achieved,
the ion source may require cleaning according to
manufacturer's instructions. In the event that the
user's instrument cannot achieve these relative ion

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abundances, but is otherwise operating properly, the
user may adopt another set of relative abundances as
performance criteria. However, these values must be
repeatable on a day-to-day basis.

11.2.2	After the mass standardization and tuning process has
been completed and the appropriate values entered into
the data system, the user should set the SIM
monitoring parameters (i.e., mass centroid and window
to be monitored) by injecting a moderatley high level
standard solution (100 ug/mL) of NDMA onto the GC/MS
in the full scan mode. The scan range should be 40 to
200 amu at a rate of 0.5 to 0.8 scans/second. The
nominal mass 42, 43, and 74 amu ions are to be used
for SIM monitoring, with the 74 amu ion employed for
NDMA quantification.

11.2.3	Before injection of NDMA standards, the GC oven
temperature is stabilized at 45°C. The filament and
electron multiplier voltage are turned off. A 2-uL
aliquot of an appropriate NDMA standard, dissolved n
acetone, is injected onto the GC/MS system using the
splitless injection technique. Concentrated NDMA
standards can be purchased from chemical supply
houses. The standards are diluted to the appropriate
concentration with acetone. CAUTION: NDMA is a
suspected carcinogen and must be handled according to
OSHA regulations. After five minutes, the electron
multiplier and filament are turned on, data
acquisition is initiated, and the oven temperature is
programmed to 250°C at a rate of 16°C/minute. After
elution of the NDMA peak from the GC/MS (Figure 3),
the data acquisition process an be halted and data
processing initiated.

11.2.4	Once the appropriate SIM parameters have been
established, as described in Section 11.2.2, the
instrument is calibrated by analyzing a range of NDMA
standards using the SIM prodecure. If necessary, the
electron multiplier voltage or amplifier gain can be
adjusted to give the desired sensitivity for standards
bracketing the range of interest. A calibration curve
of m/e 74 ion intensity versus quantity of NDMA

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injected is constructed and used to calculate NDMA
concentration in the samples.

11.3 Sample Analysis

11.3.1	The sample analysis process is the same as that
described in Section 11.2.3 for calibration standards.
Samples should be handled so as to minimize exposure
to light.

11.3.2	If a peak is observed for NDMA (within ±6 seconds of
the expected retention time), the areas (integrated
ion intensities) for m/e 42, 43, and 74 are
calculated. The area of m/e 74 peak is used to
calculate NDMA concentration. The ratios of m/e 42/74
and 43/74 ion intensities are used to determine the
certainty of the NDMA identification. Ideally, these
ratios should be within ±20% of the ratios for an
NDMA standard in order to have confidence in the peak
identification. Figure 4 illustrates the MS scan for
N-nitrosodimethylamine.

12. Calculations

12.1 Calibration Response Factors

12.1.1	Data from calibration standards are used to calculate
a response factor for NDMA. Ideally, the process
involves analysis of at least three calibration levels
of NDMA during a given day and determination of the
response factor (area/ng injected) from the linear
least squares fit of a plot of nanograms injected
versus area (for the m/e 74 ion). In general,
quantities of NDMA greater than 1000 nanograms should
not be injected because of column overloading and/or
MS response nonlinearity.

12.1.2	If substantial nonlinearity is present in the
calibration curve, a nonlinear least squares fit
(e.g., quadratic) should be employed. This process
involves fitting the data to the following equation:

Y = A + BX + CX2

where

Y = peak area
X = quantity of NDMA (ng)

A, B, and C are coefficients in the equation

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TO7-10

12.2 NDMA Concentration

12.2.1	Analyte quantities on a sample cartridge are

calculated from the following equation:

Ya = A + BXa + CX-l

where

Ya is the area of the m/e 74 ion for the sample
inj ection.

XA is the calculated quantity of NDMA (ng) on the sample
cartridge.

A, B, C are the coefficients calculated from the calibration
curve described in Section 12.1.2.

12.2.2	If instrumental response is essentially linear over
the concentration range of interest, a linear equation
(C=0 in the equation above) can be employed.

12.2.3	Concentration of analyte in the original air sample is
calculated from the following equation:

where

CA is the calculated concentration of analyte (ng/L).
V3 and XA are as previously defined in Sections 9.11 and
12.2.1, respectively.

13. Performance Criteria and Quality Assurance

13.1 Standard Operating Procedures (SOPs).

13.1.1	User should generate SOPs describing the following

activities in their laboratory: 1) assembly,
calibration, and operation of the sampling system with
make and model of equipment used; 2) preparation,
purification, storage, and handling of Thermosorb/N
cartridges and samples; 3) assembly, calibration, and
operation of the GC/MS system with make and model of
equipment used; and 4) all aspects of data recording
and processing, including lists of computer hardware
and software used.

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13.1.2	SOPs should provide specific stepwise instructions and

should be readily available to and understood by the
laboratory personnel conducting the work.

13.2	Sample Collection

13.2.1	During each sampling event, at least one clean
cartridge will accompany the samples to the field and
back to the laboratory, having been placed in the
sampler but without sampling air, to serve as a field
blank. The average amount of material found on the
field blank cartridges may be subtracted from the
amount found on the actual samples. However, if the
blank level is greater than 25% of the sample amount,
data for that component must be identified as suspect.

13.2.2	During each sampling event, at least on set of
parallel samples (two or more samples collected
simultaneously) should be collected. If agreement
between parallel samples is not generally within ±25%,
the user should collect parallel samples on a much
more frequent basis (perhaps for all sampling points).

13.2.3	Backup cartridges (two cartridges in series ) should
be collected with each sampling event. Backup
cartridges should contain less than 10% of the amount
of NDMA found in the front cartridges, or be
equivalent to the blank cartridge level, whichever is
greater.

13.2.4	NDMA recovery for spiked cartridges (using a solution-
spiking technique) should be determined before initial
use of the method on real samples. Currently
available information indicates that a recovery of 75%
or greater should be achieved.

13.3	GC/MS Analysis

13.3.1	Performance criteria for MS tuning and mass
standardization are discussed in Section 11.2 and
Table 1. Additional criteria can be used by the
laboratory, if desired. The following section provide
performance guidance and suggested criteria for
determining the acceptability of the GC/MS system.

13.3.2	Chromatographic efficiency should be evaluated daily
by the injection of NDMA calibration standards. The
NDMA peak should be plotted on an expanded time scale
so that its width at 10% of the peak height can be

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13.3.3
where

DL

A
S

13.3.4

calculated, as shown in Figure 5. The width of the
peak at 10% height should not exceed 10 seconds. More
stringent criteria may be required for certain
applications. The asymmetry factor (see Figure 5)
should be between 0.8 and 2.0.

The detection limit for NDMA is calculated from the
data obtained for calibration standards. The
detection limit is defined as

DL = A + 3 . 3 S

is the calculated detection limit in nanograms
inj ected.

is the intercept calculated in Section 12.1.2.
is the standard deviation of replicate determinations
of the lowest-level standard (at least three such
determinations are required). The lowest-level
standard should yield a signal-to-noise ratio (from
the total ion current response) of approximately 5.
Replicate GC/MS analysis of NDMA standards and/or
sample extracts should be conducted on a daily basis.
A precision of ±15% RSD or better should be achieved.

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REFERENCES

(1)	Marano, R. S., Updegrove, W. S., and Machem, R. C., "Determination of
Trace Levels of Nitrosamines in Air by Gas Chromatography/Low Resolution
Mass Spectrometry," Anal. Chem. , 54., 1947-1951 (1982).

(2)	Fine, D. H., et. al, "N-Nitrosodimethylamine in Air," Bull. Env. Cont.
Toxicol., 15, 739-746 (1976).

(3)	"EPA Method 607 - Nitrosamines," Federal Register, .49., 43313-43319,
October 26, 1984.

(4)	Anderson, R. J., "Nitrogen-Selective Detection in Gas Chromatography,"
Tracor Inc. Applications Note 79-3, Austin, Texas.

(5)	Annual Book of ASTM Standards, Part 11.03, "Atmospheric Analysis,"
American Society for Testing and Materials, Philadelphia, Pennsylvania.

(6)	Riggin, R. M., "Technical Assistance Document for Sampling and Analysis
of Toxic Organic Compounds in Ambient Air," EPA-600/4-83-027, U.S.
Environmental Protection Agency, Research Triangle Park, North Carolina,
1983 .

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MASS FLOW
CONTROLLERS

Coupling to
connect
Thermosorb® N
Adsorbent
Cortridges

VENT

(o) MASS FLOW CONTROL

ROTAMETER

VENT







—







DRY



—









TEST







PUMP





—





METER



—





V











—



















NEEDLE

Coupling to
connect

Thermosorb® N

Adsorbent

Cortridge

VALVE

(DRY TEST METER SHOULD NOT BE USED
FOR FLOW OF LESS THAN 500 ml/minutes)

(b) NEEDLE VALVE/DRY TEST METER

FIGURE 1. TYPICAL SAMPLING SYSTEM CONFIGURATION

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SAMPLING DATA SHEET
(One Sample per Data Sheet)

PROJECT:
SITE :

LOCATION:

INSTRUMENT MODEL NO:

PUMP SERIAL NO: 	

SAMPLING DATA

DATES(S) SAMPLED: 	

TIME PERIOD SAMPLED:
OPERATOR: 	

CALIBRATED BY:

Sample Number: 	

Start Time: 		Stop Time:

Time

Dry Gas

Meter
Reading

Rotameter
Reading

Flow
Rate, *Q
mL/min

Ambient
Temperature
°C

Barometric
Pressure,
mm Hg

Relative
Humidity, %

Comments

1.















2 .















3 .















4 .















N.















Total Volume Data**

Vm = (Final - Initial) Dry Gas Meter Reading, or	= 	 L

Qj + ^2 + ^3 ' ' ' Qjf x 	1		_	^

N	1000 x (Sampling Time in Minutes)		

* Flow rate from rotameter or soap bubble calibrator (specify which).
** Use data from dry gas meter if available.

FIGURE 2. EXAMPLE SAMPLING DATA SHEET

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I	I	I	I	I	I	I

12 3 4 5 6 7
TIME (MIN.)

FIGURE 3. TOTAL ION CURRENT CHROMATOGRAM RESULTING
FROM INJECTION OF 15 jllL SAMPLE OF NDMA STANDARD (10
NG//xL IN ETHANOL).

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T07-17

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T07-18

E

BC

Asymmetry Factor -Sjj

Example Colculotion:

Peak Height - DE - 100mm
10% Peak Height - BD ¦ 10mm
Peak width ot 10% Peak Height - AC = 23mm
AB = 11mm
BC — 12mm

12

Therefore: Asymmetry Factor - - 1.1

FIGURE 5. PEAK ASYMMETRY CALCULATION

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TABLE 1: SUGGESTED PERFORMANCE CRITERIA FOR RELATIVE ION
ABUNDANCES FROM FC-43 MASS CALIBRATION



% Relative

M/E

Abundance

51

1.8 ± 0.5

69

100

100

12.0 ± 1.5

119

12.0 ± 1.5

131

35.0 ± 3.5

169

3.0 ± 0.4

219

24.0 ± 2.5

264

3.7 ± 0.4

314

0.25 ± 0.1

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