Analysis of hydrazine in drinking water by isotope dilution gas chromatography/tandem mass spectrometry with derivatization and liquid-liquid extraction

Article abstract of DOI:10.1021/ac702536d

A new isotope dilution gas chromatography/chemical ionization/tandem mass spectrometric method was developed for the analysis of carcinogenic hydrazine in drinking water. The sample preparation was performed by using the optimized derivatization and multiple liquid-liquid extraction techniques. Using the direct aqueous-phase derivatization with acetone, hydrazine and isotopically labeled hydrazine-¹⁵N₂ used as the surrogate standard formed acetone azine and acetone azine-¹⁵N₂, respectively. These derivatives were then extracted with dichloromethane. Prior to analysis using methanol as the chemical ionization reagent gas, the extract was dried with anhydrous sodium sulfate, concentrated through evaporation, and then fortified with isotopically labeled N-nitrosodimethylamine-d₆ used as the internal standard to quantify the extracted acetone azine- ¹⁵N₂. The extracted acetone azine was quantified against the extracted acetone azine-¹⁵N₂. The isotope dilution standard calibration curve resulted in a linear regression correlation coefficient (R) of 0.999. The obtained method detection limit was 0.70 ng/L for hydrazine in reagent water samples, fortified at a concentration of 1.0 ng/L. For reagent water samples fortified at a concentration of 20.0 ng/L, the mean recoveries were 102% with a relative standard deviation of 13.7% for hydrazine and 106% with a relative standard deviation of 12.5% for hydrazine- ¹⁵N₂. Hydrazine at 0.5-2.6 ng/L was detected in 7 out of 13 chloraminated drinking water samples but was not detected in the rest of the chloraminated drinking water samples and the studied chlorinated drinking water sample.

Full text of DOI:10.1021/ac702536d

Anal. Chem. 2008, 80, 5449–5453
Analysis of Hydrazine in Drinking Water by Isotope
Dilution Gas Chromatography/Tandem Mass
Spectrometry with Derivatization and
Liquid-Liquid Extraction
William E. Davis, II and Yongtao Li*
Underwriters Laboratories Inc., 110 South Hill Street, South Bend, Indiana 46617
A new isotope dilution gas chromatography/chemical
ionization/tandem mass spectrometric method was de-
veloped for the analysis of carcinogenic hydrazine in
drinking water. The sample preparation was performed
by using the optimized derivatization and multiple liquid-
liquid extraction techniques. Using the direct aqueous-
phase derivatization with acetone, hydrazine and isotopi-
of textile dyes, agricultural chemicals, and pharmaceutical inter-
3
–7
mediates. Hydrazine is a hazardous substance.
Hydrazine
inhalation for a long period of time has shown adverse effects to
5
the lung, liver, spleen, and thyroid systems of animals. Hydrazine
is reported to be neurotoxic, hepatotoxic, and nephrotoxic in
6
rodents. In humans, exposure to hydrazine can damage the liver,
8
,9
kidney, and central nervous systems. In the United States,
hydrazine has not been regulated as a drinking water contaminant.
However, it has been classified as a probable human carcinogen
by the U.S. Environmental Protection Agency (EPA) and has a
15
cally labeled hydrazine-
formed acetone azine and acetone azine-
2
N used as the surrogate standard
1
5
2
N , respec-
tively. These derivatives were then extracted with dichlo-
romethane. Prior to analysis using methanol as the
chemical ionization reagent gas, the extract was dried with
anhydrous sodium sulfate, concentrated through evapora-
tion, and then fortified with isotopically labeled N-ni-
-
6
3
cancer risk level of 10 with an air concentration of 0.2 ng/m
and with a drinking water concentration of 10 ng/L.
Hydrazine drinking water contamination can originate from
military and industrial wastes, wastewater treatment plant (WWTP)
effluents, and possible formation in drinking water disinfection
processes and distribution systems. Because hydrazine is often
used for removal of halogens from wastewater treatment, it may
enter drinking water sources that are impacted by wastewater or
WWTP effluents. Particularly in recent years, reclaimed water has
been increasingly used as part of drinking water sources through
groundwater injection or surface water replenishment. Conven-
tional chlorination techniques can result in the formation of various
disinfectant byproduct (DBPs). Trihalomethanes (THMs) and
haloacetic acids (HAAs) are two classes of drinking water DBPs
currently regulated in the United States. The maximum contami-
nation levels are 80 µg/L for total THMs and 60 µg/L for the
trosodimethylamine-d
quantify the extracted acetone azine-
acetone azine was quantified against the extracted acetone
azine-15
. The isotope dilution standard calibration
curve resulted in a linear regression correlation coefficient
R) of 0.999. The obtained method detection limit was
.70 ng/L for hydrazine in reagent water samples, fortified
6
used as the internal standard to
1
5
2
N . The extracted
N
2
(
0
at a concentration of 1.0 ng/L. For reagent water samples
fortified at a concentration of 20.0 ng/L, the mean
recoveries were 102% with a relative standard deviation
of 13.7% for hydrazine and 106% with a relative standard
1
5
deviation of 12.5% for hydrazine-
.5-2.6 ng/L was detected in 7 out of 13 chloraminated
2
N . Hydrazine at
10
0
HAAs. Chloramination is an alternate disinfection technique that
can be used to reduce the formation of THMs and HAAs.
However, chloramination has been found to be increasingly
associated with the formation of nitrogenous DBPs including
drinking water samples but was not detected in the rest
of the chloraminated drinking water samples and the
studied chlorinated drinking water sample.
(
4) Toth, B. J. Natl. Cancer Inst. 1969, 42, 469–475.
Hydrazine is a highly reactive base and reducing agent, which
(5) Vernot, E. H.; MacEwen, J. D.; Bruner, R. H.; Haun, C. C.; Kinkead, E. R.;
Prentice, D. E.; Hall, A.; Schmidt, R. E.; Eason, R. L.; Hubbard, G. B.; Young,
1
,2
has a wide range of industrial and military applications. It is
used in rocket and spacecraft fuels, for removal of halogens from
wastewater, as an oxygen scavenger or corrosion inhibitor in water
boilers, in the polymerization of urethane, and in the manufacture
J. T. Fundam. Appl. Toxicol. 1985, 5, 1050–1064
6) Lambelt, C.; Shank, R. Carcinogenesis 1998, 9 (1), 65–70
(7) U.S. Environmental Protection Agency (EPA); Integrated Risk Information
System (IRIS); Hydrazine/Hydrazine Sulfate (CASRN 302-01-2); http:
www.epa.gov/iris/sunbst/0352.htm.
.
(
.
(
8) Toth, B. Hydrazines and Cancer: A guidebook on the carcinogenic activities
of hydrazines, related chemicals, and hydrazine containing natural products;
Harwood Academic Publishers: Reading, United Kingdom, 2000.
*
To whom correspondence should be addressed. E-mail: Yongtao.Li@us.ul.com.
Fax: 574-233-8207.
(
1) Budavari, S., Ed. The Merck Index: An Encyclopedia of Chemicals, Drugs,
(9) Morris, J.; Densem, J. W.; Wald, N. J.; Doll, R. Occup. Environ. Med. 1995,
52 (1), 43–45
(10) U.S. Environmental Protection Agency (EPA). Fed. Regist. 2006, 71 (2),
(40 CFR Parts 9, 141, and 142); National Primary Drinking Water
Regulations: Stage 2 Disinfectants and Disinfection Byproducts Rule, Final
Rule; http://www.epa.gov/EPA-WATER/2006/January/Day-04/w03.htm.
and Biologicals, 12th ed.; Merck Research Laboratories, Merck & Co., Inc.:
.
Whitehouse Station, NJ, 1996; pp 816-817
.
(
(
2) Schmidt, E. W. Hydrazine and Its Derivates: Preparation, Properties, and
Applications, 2nd ed.; Wiley Interscience: New York, 2001.
3) Von Burg, R.; Stout, T. J. Appl. Toxicol. 1991, 11, 447–450
.
1
0.1021/ac702536d CCC: $40.75  2008 American Chemical Society
Analytical Chemistry, Vol. 80, No. 14, July 15, 2008 5449
Published on Web 06/20/2008

1
1
N-nitrosodimethylamine (NDMA). In addition, chloramination
may also result in the formation of hydrazine that can be produced
from the reaction of monochloramine with ammonia under certain
chloraminated drinking water samples included in this work. The
reported method could be used to analyze hydrazine at concentra-
tion levels of sub to low nanogram per liter, which was sufficiently
sensitive for analyses and formation studies of hydrazine in
drinking water.
1
2–14
conditions.
Because of its high health risks and potential
formation as well as possible contamination in drinking water
source supplies, it is very important to analyze hydrazine in
drinking water, particularly in chloraminated drinking water.
Spectrophotometric or colorimetric determination was often
used for the analysis of hydrazine. Colorimetric methods could
provide a detection limit of submicrogram per liter to milligram
per liter for treated wastewater and boiler feed waters as well as
EXPERIMENTAL SECTION
Standards and Reagents. Pure acetone azine (98%), hydra-
zine dihydrochloride (>99.99%), and isotopically labeled hydrazine-
1
5
2
N dihydrochloride (98%) standards were purchased from
Sigma-Aldrich (St. Louis, MO). Isotopically labeled N-nitrosodim-
ethylamine-d (NDMA-d ) and N-nitroso-di-n-propylamine-d (NDPA-
15,16
6
6
14
natural well waters.
However, sample matrices such as colors,
d14) were purchased from Restek (Bellefonte, PA). Ultra-Resi-
turbidities, and coexisting aromatic amines could interfere with
colorimetric determination. High-performance liquid chromatog-
raphy (HPLC) with UV detection was also used to analyze
hydrazine in sludge samples after it was derivatized to hydrazones
with benzaldehyde, which provided a detection limit of 20 µg/L
for hydrazine. The derivatization HPLC/UV technique was used
in the Occupational Safety and Health Administration (OSHA)
methods for the analysis of hydrazine in air samples, which
provided a detection limit of 0.058 parts per billion (0.076
Ion chromatography was also used for hydrazine
analysis, which could separate hydrazine from monomethylhy-
drazine and 1,1-dimethylhydrazine and provided a detection limit
of 2.2 mg/L for hydrazine.
Gas chromatography (GC) was another technique used for
analyzed grade dichloromethane was purchased from Mallinckrodt
Baker (Phillipsburg, NJ). Optima grade acetone and methanol
were purchased from Fisher Scientific (St. Louis, MO). Certified
ACS grade sodium sulfite, anhydrous sodium sulfate, sodium
hydroxide, and potassium phosphate monobasic were also ob-
tained from Fisher Scientific.
17
NDMA-d
6
and NDPA-d14 were purchased as standard stock
solutions at 1.0 mg/mL in dichloromethane. The standard stock
1
5
3
18,19
solutions of hydrazine, hydrazine- N , and acetone azine were
2
µg/m ).
prepared at 1.0 mg/mL in methanol. The 4 N NaOH was prepared
in reagent water and was extracted with dichloromethane to
2
0
remove any impurities prior to use. NDMA-d and NDPA-d were
6
14
used as the internal standards (IS), which were fortified into the
1
5
2
1,22
extracts after sample extraction. Hydrazine- N was used as the
2
hydrazine analysis.
Hydrazine was derivatized with acetone
surrogate standard (SS), which was fortified into the samples
before derivatization.
Sample Collection and Storage. Drinking water samples
were collected in 250-mL precleaned amber glass bottles contain-
2 3 2 3
ing 25 mg of Na SO . Na SO was used to remove free chlorine
in an aqueous phase. The formed acetone azine had much lower
solubility in water than hydrazine and could be extracted into a
low-polarity organic solvent. A detection limit of 0.1 µg/L was
obtained for the analysis of hydrazine in steam condensate, tap
water, and distilled water. Combined with acetone derivatization
and liquid-liquid extraction (LLE) techniques, GC coupled with
chemical ionization (CI)/tandem mass spectrometry (MS/MS)
was recently used for the analysis of hydrazine in drinking water
or chloramines. The preserved samples were stored at 1-5 °C
until derivatization and extraction.
GC/CI/MS/MS. GC/MS/MS analysis was performed on
Varian 4000 GC/MS and Saturn 2200 GC/MS systems, which
included a Varian 3800GC equipped with a Varian CP8400
autosampler (Walnut Creek, CA). The separation was performed
on a Restek Rtx-5Sil MS capillary column (60 m × 0.25 mm i.d. ×
1
4
and provided a method detection limit of 3.7 ng/L.
The objective of this work was to develop a more sensitive
and reliable isotope dilution GC/CI/MS/MS method combined
with the optimized direct aqueous acetone derivatization and
multiple LLE techniques. The method sensitivity, accuracy, and
precision were investigated. Positive results were obtained for the
1
µm film thickness). The GC temperature program was initially
held at 35 °C, ramped to 100 °C at a rate of 15 °C/min and held
for 5 min, ramped to 110 °C at a rate of 3 °C/min, ramped to 180
(
(
(
11) Chen, Z.; Valentine, R. L. Environ. Sci, Technol. 2007, 41, 6059–6065
12) Yagil, G.; Anbar, M. J. Am. Chem. Soc. 1962, 84, 1797–1803
13) Shank, R. C.; Whittaker, C. Formation of genotoxic hydrazine by the
chloramination of drinking water, Technical Completion Report, Project No.
W-690; University of California, Irvine, Irvine, CA.
14) Najm. I.; Brown, N. P.; Guo, Y. C.; Hwang, C. J.; Barrett, S. E. Formation
of Hydrazine as a Chloramine By-Product, Research Project Completion
Report, Project No. 2997; American Water Works Association Research
Foundation, Denver, CO, 2006.
.
°
C at a rate of 5 °C/min and held for 2 min, and then ramped to
.
220 °C at a rate of 50 °C/min and held for 1 min. Helium was
used as the carrier gas at a constant flow of 1.1 mL/min. The GC
injector was set to 150 °C. The 2-µL extracts or calibration standard
solutions were injected onto the GC column in a splitless mode.
The MS/MS was operated in the CI mode using methanol as
the CI reagent gas. The manifold temperature, trap temperature,
and transfer line temperature were set to 40, 170, and 220 °C,
respectively. The filament emission current was set to 40 µA. The
optimized excitation amplitude was 0.4 V for hydrazine derivative
(
(
(
15) Watt, G. W.; Chrisp, J. D. Anal. Chem. 1952, 24, 2006–2008.
16) Annual Book of ASTM Standards; D1385-88: Standard Test Method for
Hydrazine in Water; American Society for Testing and Materials: Philadel-
phia, PA, 2001; Section 11, Vol. 11.01.
(
(
17) Elias, G.; Bauer, W. J. Sep. Sci. 2006, 29, 460–464
18) U.S. Department of Labor; Occupational Safety & Health Administration
OSHA); Organic Method No. 20: Hydrazine;, 1980; hppt:/www.osha.gov/
dts/sltc/methods/organic/org020/org020.html.
19) U.S. Department of Labor; Occupational Safety & Health Administration
OSHA); Organic Method No. 108: Hydrazine; 1997; hppt:/www.osha.gov/
dts/sltc/methods/organic/org108/org108.html
20) Alltech Associates, Inc. Application Note A0034: Hydrazine Analysis; 1997
21) Dee, L. A.; Webb, A. K. Anal. Chem. 1967, 39, 1165–1167
22) Selim, S. L.; Warner, C. R. J. Chromatogr. 1978, 166, 507–511
.
1
5
15
(acetone azine), hydrazine- N
and NDMA-d and 0.5 V for NDPA-d14. The mass scan ranges were
1-83 Da for NDMA-d , 90-150 Da for NDPA-d14, and 52-117
Da for acetone azine and acetone azine- N
window of 2.0 Da for NDMA-d and NDPA-d14, and 3.0 Da for
2 2
derivative (acetone azine- N ),
(
6
4
6
(
1
5
(
2
with an isolation
.
6
(
(
(
.
15
acetone azine and acetone azine- N
2
. The precursor ion > product
.
.
ion transitions used for quantitation were m/z 113 > 56 for acetone
5450 Analytical Chemistry, Vol. 80, No. 14, July 15, 2008

1
5
azine, m/z 115 > 57 for acetone azine- N
2
, m/z 81 > 46 for
NDMA-d , and m/z 145 > 97 for NDPA-d14, respectively.
6
Acetone Derivatization. For the study on the effects of the
amount of acetone on the derivatization efficiency of hydrazine,
0
5
.3, 0.4, 0.5, and 0.6 mL of acetone were added into a series of
0-mL reagent water samples that contained 0.5 g of KH PO , and
2
4
hydrazine at a concentration of 20 ng/L, which corresponded to
.6, 0.8, 1.0, and 1.2% of the sample volume, respectively. KH PO
4
0
2
was used to maintain a sample pH value of ∼5. The samples were
shaken at room temperature for 30 min and then extracted with
2
2 4
mL of dichloromethane. After drying with anhydrous Na SO ,
the extracts were analyzed and the peak areas of m/z 56 ions
resulting from the produced acetone azine were measured.
For the final optimized derivatization procedures, 25 mg of
Na
water sample. Na
Na SO and KH PO
SS solution was fortified into the sample and mixed well.
2
SO
3
and 2.5 g of KH
SO was used for sample dechlorination. After
were dissolved, 10 µL of 0.5 µg/mL hydra-
2 4
PO were also added into the 250-mL
2
3
2
3
2
4
Figure 1. Effects of the amount of acetone on derivatization
efficiency.
15
zine- N
2
The 2.5 mL of acetone was then added and mixed into the sample
for derivatization. The sample was held at room temperature for
the extract was transferred into another amber glass autosampler
vial before analysis.
Calibration and Quantitation. The procedural calibration
standard solutions were prepared by following the same optimized
3
0 min to complete the derivatization.
Liquid-Liquid Extraction. For the study on the effects of
the sample pH value on the extraction efficiency of acetone azine,
250 mL of reagent water samples containing 2.5 g of KH
2 4
PO ,
derivatization and LLE procedures as described above. Hydrazine
2
0 g of Na SO , and 2.5 mL of acetone were fortified with pure
2
4
15
and 10 µL of 0.5 µg/mL hydrazine- N
2
SS solution were added
acetone azine standard at 20 ng/L, which in turn corresponded
to 5.7 ng/L hydrazine. Na SO was used to adjust the ionic
into a series of 250-mL reagent water samples containing 25 mg
of Na SO , 2.5 g of KH PO , 20 g of Na SO , and 2.5 mL of acetone
2
4
2
3
2
4
2
4
strength. For one set of extractions, the samples were extracted
directly without adjusting the pH value of the samples. For the
other set of extractions, the samples were extracted after adjusting
the pH value to ∼10 with 5.5-6 mL of 4 N NaOH. The samples
were then extracted with one, two, and three times 20 mL of
dichloromethane, respectively. After drying the extracts with
to give concentration levels of 0.5, 2, 5, 10, 20, and 40 ng/L for
hydrazine and a constant concentration of 20 ng/L for hydrazine-
15
2 6
N SS. 10 µL of 5 µg/mL NDMA-d IS solution was added into
each extract after extraction to give a constant concentration of
2
00 ng/L.
The three types of calibrations investigated in this study
2 4
anhydrous Na SO and concentrating through evaporation, the
included procedural external standard, internal standard, and
isotope dilution standard calibrations. Peak areas were used for
the measurement of the linear regression calibration curves
measured with a 1/X weight for all calibrations. For hydrazine,
the procedural isotope dilution standard calibration curve was used
extracts were then fortified with 10 µL of 50 µg/mL NDPA-d14 IS
solution and diluted to 1.0 mL with dichloromethane prior to
analysis. The extraction recoveries were measured by using an
internal standard calibration curve resulting from a series of
calibration standard solutions that were prepared directly from
acetone azine without going through the extraction procedures
and NDPA-d14 IS.
For the final optimized LLE procedures, after adjusting the
ionic strength and pH value, the derivatized sample was extracted
with 16 mL of dichloromethane for 6 min followed with 15-min
phase separation. The same extraction procedures were repeated
for two more times. The three extracts were then combined into
a 60-mL vial. The combined extract was then dried by mixing with
to quantitate the resulted acetone azine against the resulted
15
acetone azine- N
2
SS, the procedural internal standard calibration
curve was used to quantitate the resulted acetone azine against
the NDMA-d IS, and the procedural external standard calibration
6
curve was used to quantitate the resulted acetone azine by using
its peak area versus the concentration of hydrazine. In addition,
the injection was evaluated by measuring the recoveries of NDMA-
6
d IS using an external standard calibration curve. Moreover, the
1
5
resulted acetone azine- N
2
could be quantitated against the
1
5
1
2 g of anhydrous Na
was concentrated to ∼5 mL using a Zymark TurboVap evaporator
Caliper Life Sciences, Hopkinton, MA), it was then transferred
2 4
SO for 30 min. After the combined extract
NDMA-d IS. The recoveries of acetone azine- N could be used
6
2
to evaluate the derivatization and extraction efficiency of hydra-
zine, which subsequently reflected the method sensitivity.
(
into a 15-mL conical tube and was continuously concentrated down
to ∼0.9 mL. The extract was transferred into a 1-mL volumetric
RESULTS AND DISCUSSION
flask, fortified with 10 µL of 5 µg/mL NDMA-d
6
IS solution, diluted
Derivatization and Liquid-Liquid Extraction. The effects
of the amount of acetone on the derivatization efficiency of
hydrazine were studied by measuring the peak areas of acetone
azine resulting from the reagent water samples with varied sample-
to-acetone volume ratios. As shown in Figure 1, the highest peak
area of acetone azine was obtained from the reagent water sample
to the 1.0-mL mark with dichloromethane, and then transferred
into an amber autosampler vial. In to order to achieve the
maximum removal of water from the extract, 0.4 g of anhydrous
Na
2 4
SO was added into the autosampler vial and the resultant
mixture placed in a freezer for a minimum of 6 hours. Finally,
Analytical Chemistry, Vol. 80, No. 14, July 15, 2008 5451

Figure 2. Effects of extraction times on the recoveries of acetone
azine.
containing 0.5 mL or 1.0% acetone. Therefore, 2.5 mL of acetone
was used for 250-mL samples in the following studies.
In the early development of LLE procedures, a series of 250-
Figure 3. Procedural calibration curves of hydrazine with 250-mL
sample extracted. Isotope dilution calibration, hydrazine- N2 used
as the SS; internal standard calibration, NDMA-d6 used as the IS.
15
mL reagent water samples containing 2.5 g of KH
2 4
PO , 2.5 mL of
acetone, and varied amounts of Na SO were fortified with acetone
2
4
shown in Figure 3, all three procedural calibration curves were
linear in the studied concentration range but the procedural
isotope dilution standard calibration resulted in a slightly better
linearity. The obtained linear regression correlation coefficients
azine at 12 ng/L. The samples were extracted with 20 mL of
dichloromethane for 2, 4, 6, 8, 10, 12, 14, and 16 min, respectively.
The obtained recovery differences of acetone azine were not
significant for the extractions using 20, 40, and 60 g of Na
with an extraction time of 2-16 min. Therefore, 20 g or 8% Na
2
SO
SO
4
(
R) were 0.999 for the procedural isotope dilution standard
calibration, 0.997 for the internal standard calibration curve, and
.994 for the external standard calibration curve, respectively.
2
4
and an extraction time of 6 min were used for the later develop-
ment of LLE procedures, considering the potential difference in
the ionic strength of sample matrixes.
Figure 2 shows the effects of sample pH values and multiple
extractions on the recoveries of acetone azine. As shown in Figure
0
Therefore, the procedural isotope dilution standard calibration was
used in the following studies on the demonstration of method
sensitivity, accuracy, and precision and drinking water samples
and as well as matrix effects.
Chromatograms. Figure 4 shows the GC/CI/MS/MS chro-
matograms resulting from the lowest calibration standard solution
with at a concentration of 0.5 ng/L for hydrazine under the
optimized sample preparation and instrumental conditions. As
shown in Figure 4, sharp and symmetric peaks were obtained for
2, the multiple extractions without adjusting the sample pH value
before extraction did not significantly increase the recoveries of
acetone azine. The obtained absolute recoveries were 8.2, 8.7, and
10.6% for one, two, and three dichloromethane extractions,
respectively. However, the recoveries of acetone azine were
significantly increased after the sample pH was adjusted to ∼10.
The obtained absolute recoveries were 37.0, 54.6, and 66.7% for
one, two, and three dichloromethane extractions, respectively.
Therefore, the multiple LLE with a pH adjustment was included
in the final optimized LLE procedures.
the IS (NDMA-d
6
), derivatized hydrazine, and derivatized hydra-
15
zine- N
2
SS. Their retention times were approximately 9.08, 12.37,
and 12.37 min, respectively. The measured peak-to-peak signal-
to-noise ratio (ptp S/N) was 320 for the acetone azine resulting
from hydrazine at 0.5 ng/L.
1
5
2
Calibrations. Hydrazine- N was selected as the SS because
1
5
Sensitivity, Precision, and Accuracy. Method sensitivity,
accuracy, and precision were studied through the measurement
of seven replicate fortified reagent water samples. The method
detection limit (MDL) was measured from 3.14 times the standard
deviation of the seven analyses (3.14 is the Student t value for
2
the isotopically labeled nitrogen ( N ) would be retained in the
final acetone azine structure, which would distinguish the precur-
sor and product ion masses from those resulting from the
hydrazine acetone derivative. In theory, the procedural isotope
1
5
2
dilution using hydrazine- N , an isotopically labeled hydrazine
2
3
the 99% confidence level with -1 degrees of freedom). The
accuracy was measured as the mean percent relative recovery.
The precision was measured as the percent relative standard
deviation (RSD).
analogue, could effectively compensate for the effects of matrix
interferences, procedural performance variations on the derivati-
zation, extraction efficiency, and precision of hydrazine, and
instrument performance variations resulting from the injection,
15
As shown in Table 1, the obtained MDL of hydrazine was 0.70
ng/L for seven reagent water samples fortified at 1.0 ng/L. The
2
separation, and detection processes. However, hydrazine- N was
very expensive. Therefore, procedural external standard and
internal standard calibrations were also evaluated in a concentra-
tion range of 0.5-40 ng/L for the measurement of hydrazine. As
(
23) Glaser, J. A.; Forest, D. L.; McKee, G. D.; Quave, S. A.; Budde, W. L.
Environ. Sci. Technol. 1981, 15, 1426–1435
.
5452 Analytical Chemistry, Vol. 80, No. 14, July 15, 2008

Figure 4. GC/CI/MS/MS chromatograms of selected quantitation ions. IS, m/z 46 ion resulting from NDMA-d6 at 200 ng/L; hydrazine, m/z 56 ion of
15
15
acetone azine resulting from hydrazine at 0.5 ng/L (m/z 56); and SS, m/z 57 ion of acetone azine- N2 resulting from hydrazine- N2 at 20 ng/L.
Table 1. Method Sensitivity, Precision, and Accuracy
Based on Seven Replicate Fortified Reagent Water
Samples
Table 2. Results of Drinking Water (DW) Samples and
Matrix Studies
a
sample
fortified
mean
fortified
mean
recovery
(%)
concentration concentration recovery RSD
concentration
RSD
(%)
MDL
(ng/L)
DW sample
(ng/L)
(ng/L)
(%)
(%)
(
ng/L)
chlorinated S1
<0.5
0.50
<0.5
2.6
20.0
20.0
122
132
na
118
na
na
na
na
na
na
na
na
na
na
6.6
9.3
na
2.9
na
na
na
na
na
na
na
na
na
na
hydrazine
1.0
82
102
106
27.4
13.7
12.5
0.70
chloraminated S1
chloraminated S2
chloraminated S3
chloraminated S4
chloraminated S5
chloraminated S6
chloraminated S7
chloraminated S8
chloraminated S9
chloraminated S10
chloraminated S11
chloraminated S12
chloraminated S13
a
b
2
0.0
na
na
1
5
hydrazine- N2
20.0
na
20.0
na
na
na
na
na
na
na
na
na
na
1.8
a
na, not applicable.
1.6
<0.5
0.86
0.90
<0.5
<0.5
0.73
<0.5
<0.5
mean relative recoveries were 102% with a RSD of 13.7% for
hydrazine at a concentration of 20.0 ng/L and 106% with a RSD
1
5
2
of 12.5% for hydrazine- N at a concentration of 20.0 ng/L.
Drinking Water Analysis and Matrix Study. Fourteen
drinking water samples from 6 different utilities were studied,
which included one chlorinated drinking water sample and
thirteen chloraminated drinking water samples. Three samples
were selected and fortified with hydrazine at 20.0 ng/L in triplicate
to study the matrix effects on recoveries and precision. As shown
in Table 2, hydrazine was not detected above the lowest calibration
point of 0.5 ng/L in the chlorinated drinking water and six
chloraminated drinking water samples, but was detected in seven
chloraminated drinking water samples at concentrations ranging
from 0.5 to 2.6 ng/L. For the matrix spikes, the obtained mean
recoveries varied from 118 to 132% with a RSD of 2.9 to 9.3%.
a
The mean recovery and RSD results were based on triplicate
fortified DW samples. Chloraminated samples S1 and S2 were from
the same utility. Chloraminated samples S3-S6 were from the same
b
utility. Chloraminated samples S7-S10 were from the same utility. na,
not available.
reported method was successfully applied to drinking water
samples. Hydrazine at sub to low nanogram per liter levels was
detected in some chloraminated drinking water samples, which
indicates that it is very important to further study the occurrence
concentration levels and formation potential of hydrazine in
chloraminated drinking water.
CONCLUSIONS
ACKNOWLEDGMENT
This paper clearly demonstrated that the isotope dilution GC/
CI/MS/MS method, combined with the optimized direct aqueous-
phase acetone derivatization and multiple LLE techniques, pro-
vided good sensitivity, recoveries, and precision for the analysis
of hydrazine in drinking water. The procedural isotope dilution
calibration with good linearity could effectively compensate for
matrix interferences and procedural performance variations. The
Special thanks to Dr. Yingbo C. Guo (Metropolitan Water
District of Southern California, La Verne, CA) for the helpful
discussion in the method development.
Received for review December 14, 2007. Accepted May
13, 2008.
AC702536D
Analytical Chemistry, Vol. 80, No. 14, July 15, 2008 5453