Analysis of N-nitrosodimethylamine

(NDMA) in Water using GC Triple

Quadrupole Mass Spectrometry
Authors
Alandra Kahl, Darryl Jones, Lisa Lowe,
and Shane Snyder
University of Arizona
Tucson, Arizona
USA
Anthony Macherone
Agilent Technologies, Inc.
Wilmington, DE
USA
Application Note
Abstract
A method was developed on the Agilent 7890A Series GC and an Agilent 7000B
Triple Quadrupole GC/MS mass spectrometer in positive chemical ionization (PCI)
mode that provides sensitivity of one part per trillion (ppt) and lower for N-nitrosodi-
methylamine (NDMA). The method further provides an acceptable alternative to the
commonly used ion trap MS method for those laboratories that do not have an ion
trap instrument. The limit of detection (LOD) was 0.20 ppt, and the limit of quantita-
tion (LOQ) was determined to be 0.56 ppt.
2
Introduction
Chloramination is used in wastewater treatment facilities to
reduce trihalomethanes (THMs) which have been associated
with an increased risk of bladder cancer and are released into
water sources through both industrial and anthropogenic
sources. However, nitrosamines like NDMA are inadvertent
by-products of wastewater treatment through chloramination.
NDMA itself has been classified by national and international
regulatory authorities as a probable human carcinogen, and
numerous laboratory animal studies have linked NDMA
exposure to various cancers.
NDMA is considered a priority pollutant, but few regulatory
limits exist for the concentration of NDMA in the environment
and drinking water in particular. However, a number of inter-
national, national and subnational authorities have set regula-
tory guidelines or assessment levels for nitrosamines in drink-
ing water. In 1989, NDMA was found in a drinking water well
in northern California and the state has since established a
notification level of 10 ng/L (ppt), and a response level of
300 ng/L, at which removal of the water source from service
is recommended. Internationally, in 2008 the World Health
Organization (WHO) added NDMA to its guidelines for drink-
ing water quality. In March 2010, Health Canada proposed a
maximum acceptable concentration for NDMA in drinking
water of 40 ng /L.
As of October 2009, the US Environmental Protection Agency
(EPA) listed five nitrosamines, including NDMA, on its candi-
date list of priority drinking water contaminants for which the
EPA will research whether regulations are needed. If NDMA
or other nitrosamines become regulated drinking water conta-
minants, robust, sensitive analytical methods will be required
for compliance monitoring [1].
This application note describes a GC/MS/MS method that
yields an LOD of 0.20 ppt and an LOQ of 0.56 ppt.
Experimental
Standards and Reagents
NDMA standard was obtained from Supelco, and d6-NDMA
surrogate and N-nitroso-di-n-propylamine-d14 (NDPA- d14)
internal standard were obtained from Cambridge Isotope
Laboratories Inc. Standards were made up by weight in
dichloromethane. Coconut charcoal SPE cartridges, 80/120
mesh, were obtained from Restek. Dichloromethane and
methanol were obtained from Fisher Scientific. HPLC grade
water was used to prepare the calibration standards.
Instruments
This method was developed on an Agilent 7890A Series GC
equipped with an S/SL inlet and coupled to an Agilent 7000B
Triple Quadrupole GC/MS in positive chemical ionization (PCI)
mode. Table 1 lists the instrument conditions.
Table 1. Agilent 7890A Series Gas Chromatograph and Agilent 7000B
Triple Quadrupole Mass Spectrometer Conditions
GC run conditions
Analytical columns DB-WAXETR 30 m 0.25 mm, 0.25 m
(p/n 122-7332)
Inlet temperature 200 C
Injection mode Splitless 5-L injection.
Flow Constant flow at 1.7 mL/min
Oven program 40 C for 3 minutes
then 10 C/min to 110 C for 0 minutes
then 15 C/min to 200 C for 0 minutes
then 40 C/min to 240 C for 0 minutes
Carrier gas Helium Ultra High Purity. Constant flow.
Transfer line temperature 240 C
PCI MS conditions
Tune PCI Autotune
EMV gain 15
Acquisition parameters PCI positive mode with single reaction monitoring
(SRM)
Reagent gas Ammonia, 20 % flow
Collision gas Nitrogen, constant flow, 1.5 mL/min
Quench gas Helium, constant flow, 2.25 mL/min
Solvent delay 6.0 minutes
MS temperatures Source 200 C; Quadrupole 150 C
3
Sample Preparation
One-half liter of each water sample spiked with NDMA stan-
dard at a given concentration was extracted using solid phase
extraction (SPE) procedures similar to those described else-
where [1]. NDMA-d6-was added to samples as a surrogate
prior to sample preparation to monitor extraction efficiency.
The eluent from the SPE column was reduced to 0.5 mL using
a gentle stream of nitrogen at room temperature. The sample
was then brought to 1.0 mL with dichloromethane. The final
concentration factor was 500 fold. NDPA-d14 was then added
as an internal standard.
Acquisition Parameters
The mass spectrometer single reaction monitoring (SRM)
acquisition parameters are given in Table 2.
Table 2. Agilent 7000B Triple Quadrupole GC/MS Acquisition Parameters
PCI with ammonia mode
Nitrosamine RT (min) SRM Dwell time (ms) Collision energy (EV) Gain
N-Nitrosodimethylamine (NDMA) 9.141 92 & 75 30 12 15
Deuterated N-Nitrosodimethylamine (NDMA-d6) 9.133 98 & 81 30 12 15
Deuterated N-Nitrosodi-n-propylamine (NDPA-d14) 11.862 162 & 50
162 & 145
30
30
12
12
15
15
Results and Discussion
PCI with Ammonia
Using the 7000 Triple Quadrupole GC/MS in positive chemical
ionization (PCI) mode with ammonia as the reagent gas and
single reaction monitoring (SRM) enables the low detection
limits that may be required to monitor NDMA in environmen-
tal water samples. Figure 1 illustrates an LOQ with a signal-to-
noise (S/N) ratio of 12:1 for NDMA at 0.56 ppt (height, peak-
to-peak, 30 second noise region over 8.48.9 minutes).
10
2
0
0.1
0.2
0.3
0.4
0.5
0.6
0.7
0.8
0.9
1.0
1.1
1.2
1.3
1.4
1.5
1.6
1.7
1.8
1.9
2.0
2.1
2.2
2.3
Noise (peak-to-peak) = 17.02; SNR (9.010 minutes) = 12.7
* 9.010
689.58
Acquisition time (min)
C
o
u
n
t
s
7 7.2 7.4 7.6 7.8 8 8.2 8.4 8.6 8.8 9 9.2 9.4 9.6 9.8 10 10.2 10.4 10.6 10.8 11 11.2
Noise region:
8.48.9 minutes
Figure 1. Single Reaction Monitoring (SRM) chromatogram of 0.56 ppt NDMA standard.
4
Figure 2 shows an overlay of the SRM chromatograms of the
seven calibration levels and Figure 3 illustrates the corre-
sponding calibration curve with a linear correlation coefficient
of > 0.999.
Figure 2. Overlaid SRM chromatograms of NDMA standards.
Figure 3. Calibration curve for NDMA standards from 0.56 to 360 ppt in PCI Ammonia mode, after
accounting for 500 fold concentration during sample preparation.
NDMA: overlay of 7 levels 10
4
0
0.1
0.2
0.3
0.4
0.5
0.6
0.7
0.8
0.9
1.0
1.1
1.2
1.3
Acquisition time (min)
C
o
u
n
t
s
8.40 8.46 8.52 8.58 8.64 8.70 8.76 8.82 8.88 8.94 9.00 9.06 9.12 9.18 9.24 9.30 9.36 9.40
ppt NDMA
0.560
1.125
2.250
4.500
9.000
18.000
36.000
NDMA - 7 Levels, 7 Levels Used, 7 Points, 7 Points Used, 0 QCs
Relative concentration
-2 0 2 4 6 8 10 12 14 16 18 20 22 24 26 28 30 32 34 36 38
R
e
l
a
t
i
v
e

r
e
s
p
o
n
s
e
s
0
0.2
0.4
0.6
0.8
1.0
1.2
1.4
1.6
1.8
2.0
2.2
2.4
2.6
2.8
y = 0.072178*x + 0.030053
R
2
= 0.99968047
Type:Linear, Origin:Ignore, Weight:None
5
With this data, minimum reportable limits such as the LOD
and LOQ were determined as 0.20 ppt and 0.56 ppt, respec-
tively at the 95% confidence level for 10 replicate injections
by using a one-tail Student-T test with n-1 degrees of free-
dom. Figure 4 shows typical lab and field blank detection
Figure 4. NDMA SRM chromatograms of lab and field blanks.
Figure 5. NDMA and NDMA-d6 SRM channels of dichloromethane solvent blank and water sample
illustrating clean solvent background and 3.4 ppt NDMA detected in the water sample.
levels of NDMA. Figure 5 illustrates the NDMA and NDMA-d6
SRM channels of dichloromethane solvent blank and actual
drinking water sample from a city in the western United
States that was determined to contain 3.4 ppt NDMA.
10
2
10
2
0
0.4
0.8
1.2
1.6
2.0
2.4
0
0.2
0.4
0.6
0.8
1.0
1.2
1.4
1.6
Acquisition time (min)
6.2 6.4 6.6 6.8 7.0 7.2 7.4 7.6 7.8 8.0 8.2 8.4 8.6 8.8 9.0 9.2 9.4 9.6 9.8 10.0 10.2 10.4 10.6
Lab blank
Field blank
C
o
u
n
t
s
C
o
u
n
t
s
1
2
+CI MRM CID@12.0 (92.0000 -> 75.0000) 091212_dcm_blank_10.D
1
0
0
2
+CI MRM CID@12.0 (98.0000 -> 81.0000) 091212_dcm_blank_10.D
0
1
2
+CI MRM CID@12.0 (92.0000 -> 75.0000) 091212_srwtp_finaleff_0900_082812.D
9.000
4661
0
0.5
1
1.5
2
2.5
+CI MRM CID@12.0 (98.0000 -> 81.0000) 091212_srwtp_finaleff_0900_082812.D
8.995
6963
Acquisition time (min)
C
o
u
n
t
s
C
o
u
n
t
s
C
o
u
n
t
s
C
o
u
n
t
s
8.54 8.58 8.62 8.66 8.7 8.74 8.78 8.82 8.86 8.9 8.94 8.98 9.02 9.06 9.1
Solvent blank NDMA channel
Solvent blank NDMA-d6 channel
Water NDMA channel
Water NDMA-d6 channel
10
3
10
3
10
3
10
3
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Agilent shall not be liable for errors contained herein or for incidental or consequential
damages in connection with the furnishing, performance, or use of this material.
Information, descriptions, and specifications in this publication are subject to change
without notice.
Agilent Technologies, Inc., 2013
Printed in the USA
January 22, 2013
5991-1801EN
Conclusion
This method, using the Agilent 7890A GC and 7000B Triple
Quadrupole GC/MS system, yields limits of detection and
quantification of less than 1 ppt NDMA in water matrices.
Reference
1. J.W. Munch, M.V. Basset. US EPA Method 521, Version
1. September, 2004.
For More Information
These data represent typical results. For more information on
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www.agilent.com/chem.