Accessed from 80.28.157.
17 by quimica on Fri Aug 08 08:08:08 EDT 2014
USP 37
Reagent Water Control: Use a suitable quantity of Re-
agent Water obtained at the same time as that used in the
preparation of the Standard Solution and the System Suitabili-
ty Solution.
Water Sample: Obtain an on-line or off-line sample that
suitably reflects the quality of water used.
Other Control Solutions: Prepare appropriate reagent
blank solutions or other specified solutions needed for estab-
lishing the apparatus baseline or for calibration adjustments
following the manufacturer’s instructions, and run the ap-
propriate blanks to zero the instrument, if necessary.
System Suitability: Test the Reagent Water Control in the
apparatus, and record the response, rW. Repeat the test us-
ing the Standard Solution, and record the response, rS. Cal-
culate the corrected Standard Solution response, which is al-
so the limit response, by subtracting the Reagent Water Con-
trol response from the response of the Standard Solution.
The theoretical limit of 0.50 mg/L of carbon is equal to the
corrected Standard Solution response, rS − rW. Test the System
Suitability Solution in the apparatus, and record the re-
sponse, rSS. Calculate the corrected System Suitability Solution
response by subtracting the Reagent Water Control response
from the response of the System Suitability Solution, rSS − rW.
Calculate the percent response efficiency for the System Suit-
ability Solution:
% response efficiency = 100[(rSS − rW)/(rS − rW)]
where rSS is the instrument response to the System Suitability
Solution; rW is the instrument response to the Reagent Water
Control; and rS is the instrument response to the Standard
Solution. The system is suitable if the percent response effi-
ciency is not less than 85% and not more than 115%.
Procedure: Perform the test on the Water Sample, and re-
cord the response, rU. The Water Sample meets the require-
ments if rU is not more than the limit response, rS − rW. This
method can be performed using on-line or off-line instru-
mentation that meets the Apparatus Requirements.
STERILE WATER
The following sections apply to tests for Sterile Water for
Injection, Sterile Purified Water, Sterile Water for Irrigation, and
Sterile Water for Inhalation.
Follow the requirements in Bulk Water, with the following
exceptions.
Apparatus Requirements: In addition to the Apparatus
Requirements in Bulk Water, the apparatus must have a man-
ufacturer’s specified limit of detection of 0.10 mg/L (0.10
ppm) or lower of carbon.
Reagent Water: Use water having a TOC level of not
more than 0.50 mg/L. [NOTE—A conductivity requirement
may be necessary in order to ensure method reliability.]
Standard Solution: Unless otherwise directed in the in-
dividual monograph, dissolve in the Reagent Water an accu-
rately weighed quantity of USP Sucrose RS to obtain a solu-
tion having a concentration of 19.0 mg/L of sucrose (8.0
mg/L of carbon).
System Suitability Solution: Dissolve in Reagent Water
an accurately weighed quantity of USP 1,4-Benzoquinone
RS to obtain a solution having a concentration of 12.0 mg/L
(8.0 mg/L of carbon).
Official from August 1, 2014
Copyright (c) 2014 The United States Pharmacopeial Convention. All rights reserved.
Physical Tests / á645ñ Water Conductivity 311
Water Sample: Obtain a sample that suitably reflects
the quality of water used. Before opening, vigorously agitate
the package to homogenize the water sample. Several pack-
ages may be required in order to collect sufficient water for
analysis.
System Suitability: Test the Reagent Water Control in
the apparatus, and record the response, rW. Repeat the test
using the Standard Solution, and record the response, rS. Cal-
culate the corrected Standard Solution response, which is al-
so the limit response, by subtracting the Reagent Water Con-
trol response from the response of the Standard Solution.
The theoretical limit of 8.0 mg/L of carbon is equal to the
corrected Standard Solution response, rS − rW. Test the System
Suitability Solution in the apparatus, and record the re-
sponse, rSS. Calculate the corrected System Suitability Solution
response by subtracting the Reagent Water Control response
from the response of the System Suitability Solution, rSS − rW.
Calculate the percent response efficiency for the System Suit-
ability Solution:
% response efficiency = 100[(rSS − rW)/(rS − rW)]
General Chapters
where rSS is the instrument response to the System Suitability
Solution; rW is the instrument response to the Reagent Water
Control; and rS is the instrument response to the Standard
Solution. The system is suitable if the percent response effi-
ciency is not less than 85% and not more than 115%.
Procedure: Perform the test on the Water Sample, and
record the response, rU. The Water Sample meets the re-
quirements if rU is not more than the limit response, rS − rW,
determined in the System Suitability requirements in Sterile
Water.
á645ñ WATER CONDUCTIVITY
Change to read:
s INTRODUCTIONsUSP37
Electrical conductivity in water is a measure of the ion-fa-
cilitated electron flow through it. Water molecules dissociate
into ions as a function of pH and temperature and result in a
very predictable conductivity. Some gases, most notably
carbon dioxide, readily dissolve in water and interact to
form ions, which predictably affect conductivity salso.sUSP37
For the purpose of this discussion, these ions and their re-
sulting conductivity can be considered intrinsic to the water.
sWater conductivity is also affected by the presence of ex-
traneous ions. The extraneous ions used in modeling the
conductivity specifications described below are the chloride
and ammonia ions. The conductivity of the ubiquitous
chloride ion (at the theoretical endpoint concentration of
0.47 ppm when chloride was a required attribute test in USP
22 and earlier revisions) and the ammonium ion (at the limit
of 0.3 ppm) represents a major portion of the allowed water
ionic impurity level. A balancing quantity of anions (such as
chloride, to counter the ammonium ion) and cations (such
as sodium, to counter the chloride ion) is included in this al-
 Accessed from 80.28.157.17 by quimica on Fri Aug 08 08:08:08 EDT 2014
312 á645ñ Water Conductivity / Physical Tests
lowed impurity level to maintain electroneutrality. Extrane-
ous ions such as these may have a significant effect on the
water’s chemical purity and suitability for use in pharma-
ceutical applications.
The procedure in the section Bulk Water is specified for
measuring the conductivity of waters such as Purified Water,
Water for Injection, Water for Hemodialysis, and the conden-
sate of Pure Steam. The procedure in the section Sterile Wa-
ter is specified for measuring the conductivity of waters such
as Sterile Purified Water, Sterile Water for Injection, Sterile Wa-
ter for Inhalation, and Sterile Water for Irrigation.
The procedures below shall be performed using instru-
mentation that has been calibrated, has conductivity sensor
cell constants that have been accurately determined, and
has a temperature compensation function that has been dis-
abled for Bulk Water Stage 1 testing. For both online and
offline measurements, the suitability of instrumentation for
quality control testing is also dependent on the sampling lo-
cation(s) in the water system. The selected sampling instru-
ment location(s) must reflect the quality of the water
General Chapters
used.sUSP37
Change to read:
INSTRUMENT SPECIFICATIONS AND
OPERATING PARAMETERS
sWater conductivity must be measured accurately with
calibrated instrumentation. An electrical conductivity meas-
urement consists of the determination of the conductance,
G (or its inverse, resistance, R), of the fluid between and
around the electrodes. The conductance (1/R) is directly af-
fected by the geometrical properties of the electrodes; i.e.,
the conductance is inversely proportional to the distance (d)
between the electrodes and proportional to the area (A) of
the electrodes. This geometrical ratio (d/A) is known as the
cell constant, Q. Thus the measured conductance is normal-
ized for the cell constant to determine the conductivity, k,
according to the following equation:
conductivity, k (S/cm) = Q (cm–1)/R (W)
It is the cell constant and the resistance measurement that
must be verified and adjusted, if necessary.
Cell constant: The cell constant must be known within
±2%. The cell constant can be verified directly by using a
solution of known or traceable conductivity, or indirectly by
comparing the instrument reading taken with the conduc-
tivity sensor in question to readings from a conductivity sen-
sor of known or traceable cell constant. If necessary, adjust
the cell constant following the manufacturer¢s instrument
protocol. The frequency of verification/calibration is a func-
tion of the sensor design.
Resistance measurement: Calibration (or verification) of
the resistance measurement is accomplished by replacing
the conductivity sensor electrodes with precision resistors
having standards traceable to NIST or equivalent national
authorities in other countries (accurate to ±0.1% of the sta-
ted value) to give a predicted instrument conductivity re-
sponse. The accuracy of the resistance measurement is ac-
ceptable if the measured conductivity with the traceable re-
sistor is within ±0.1 mS/cm of the calculated value according
Official from August 1, 2014
Copyright (c) 2014 The United States Pharmacopeial Convention. All rights reserved.
USP 37
to the equation above. For example, the traceable resistor is
50 kW, and the cell constant, Q, is 0.10 cm–1. The calculated
value is 2.0 × 10–6 S/cm or 2.0 mS/cm. The measured value
should be 2.0 ± 0.1 mS/cm. The instrument must have a
minimum resolution of 0.1 mS/cm on the lowest range.
The target conductivity value(s) should be based on the
type of water to be analyzed, and it should be equal to or
less than the water conductivity limit for that type of water.
Multiple measuring circuits may be embedded in the meter
or the sensor, and each circuit may require separate verifica-
tion or calibration before use. The frequency of recalibration
is a function of instrument system design.
System verification: The cell constant of the user’s sensor
can be determined with the user’s resistance measurement
system, or the cell constant can be determined with an in-
dependent resistance measurement system. If the cell con-
stant is determined with an independent resistance meas-
urement system, it is recommended that the user verify that
the sensor has been properly connected to the resistance
measurement system to ensure proper performance. Verifi-
cation can be made by comparing the conductivity (or resis-
tivity) values displayed by the measuring equipment with
those of an external calibrated conductivity-measuring de-
vice. The two non–temperature-compensated conductivity
(or resistivity) values should be equivalent to or within ±5%
of each other, or should have a difference that is acceptable
on the basis of product water criticality and/or the water
conductivity ranges in which the measurements are taken.
The two conductivity sensors should be positioned close
enough together to measure the same water sample at the
same temperature and water quality.
Temperature compensation and temperature
measurements: Because temperature has a substantial ef-
fect on conductivity readings of specimens at high and low
temperatures, many instruments automatically correct the
actual reading to display the value that theoretically would
be observed at the nominal temperature of 25°. This is typi-
cally done using a temperature sensor embedded in the
conductivity sensor and a software algorithm embedded in
the instrument. This temperature compensation algorithm
may not be accurate for the various water types and impuri-
ties. For this reason, conductivity values used in the Stage 1
test for Bulk Water are non–temperature-compensated
measurements. Other conductivity tests that are specified
for measurement at 25° can use either temperature-com-
pensated or non–temperature-compensated measurements.
A temperature measurement is required for the Stage 1
test or for the other tests at 25°. It may be made using the
temperature sensor embedded in the conductivity cell sen-
sor. An external temperature sensor positioned near the
conductivity sensor is also acceptable. Accuracy of the tem-
perature measurement must be ±2°.sUSP37
Change to read:
BULK WATER
The procedure and test limits in this section are intended
for Purified Water, Water for Injection, Water for Hemodialysis,
the condensate of Pure Steam, and any other monographs
that specify this section.
Accessed from 80.28.157.17 by quimica on Fri Aug 08 08:08:08 EDT 2014
USP 37 Physical Tests / á645ñ Water Conductivity 313

sThis is a three-stage test method to accommodate online
or offline testing. Online conductivity testing provides real-
time measurements and opportunities for real-time process
control, decision, and intervention. Precautions should be
taken while collecting water samples for offline conductivity
measurements. The sample may be affected by the sam-
pling method, the sampling container, and environmental
factors such as ambient carbon dioxide concentration and
organic vapors. This procedure can be started at Stage 2 if
offline testing is preferred.sUSP37
Procedure
ature, if necessary, and, while maintaining it at 25 ± 1°, be-
gin vigorously agitating the test specimen while periodically
observing the conductivity. When the change in conductivi-
ty (due to uptake of atmospheric carbon dioxide) is less
than a net of 0.1 mS/cm per 5 min, note the conductivi-
ty. s[NOTE—Conductivity measurements at this stage may
be temperature-compensated to 25° or non–temperature-
compensated.]sUSP37
5. If the conductivity is not greater than 2.1 mS/cm, the
water meets the requirements of the test for conductivity. If
the conductivity is greater than 2.1 mS/cm, proceed with
Stage 3.

STAGE 1 STAGE 3

Stage 1 is intended for online measurement or may be
performed offline in a suitable container.
1. Determine the temperature of the water and the con-
ductivity of the water with a non–temperature-compensated
conductivity reading.
6. Perform this test within approximately 5 min of the
conductivity determination in step 5, while maintaining the
sample temperature at 25 ± 1°. Add a saturated potassium
chloride solution to the same water sample (0.3 mL per 100
mL of the test specimen), and determine the pH to the

General Chapters
2. Using Table 1, find the temperature value that is NMT nearest 0.1 pH unit, as directed in pH á791ñ.
the measured temperature, i.e., the next lower temperature. 7. Referring to Table 2, determine the conductivity limit at
The corresponding conductivity value on this table is the the measured pH value. If the measured conductivity in step
limit. [NOTE—Do not interpolate.] 4 is sNMT the table valuesUSP37 determined in step 6, the
3. If the measured conductivity is NMT the table val- water meets the requirements of the test for conductivity. If
ue sdetermined in step 2,sUSP37 the water meets the require- either the measured conductivity is greater than this value
ments of the test for conductivity. If the conductivity is or the pH is outside the range of 5.0–7.0, the water does
higher than the table value, proceed with Stage 2. not meet the requirements of the test for conductivity.
Table 1. Stage 1—Temperature and Conductivity Table 2. Stage 3—pH and Conductivity Requirements
Requirements (for atmosphere- and temperature-equilibrated samples only)
(for non–temperature-compensated conductivity measurements only) pH Conductivity Requirement (mS/cm)
Temperature Conductivity Requirement (mS/cm) 5.0 4.7
0 0.6 5.1 4.1
5 0.8 5.2 3.6
10 0.9 5.3 3.3
15 1.0 5.4 3.0
20 1.1 5.5 2.8
25 1.3 5.6 2.6
30 1.4 5.7 2.5
35 1.5 5.8 2.4
40 1.7 5.9 2.4
45 1.8 6.0 2.4
50 1.9 6.1 2.4
55 2.1 6.2 2.5
60 2.2 6.3 2.4
65 2.4 6.4 2.3
70 2.5 6.5 2.2
75 2.7 6.6 2.1
80 2.7 6.7 2.6
85 2.7 6.8 3.1
90 2.7 6.9 3.8
95 2.9 7.0 4.6
100 3.1
STERILE WATER
STAGE 2
The procedure and test limits are intended for Sterile Puri-
4. Transfer a sufficient amount of water ssUSP37 to a suita- fied Water, Sterile Water for Injection, Sterile Water for Inhala-
ble container, and stir the test specimen. Adjust the temper-

Official from August 1, 2014

Copyright (c) 2014 The United States Pharmacopeial Convention. All rights reserved.
 Accessed from 80.28.157.17 by quimica on Fri Aug 08 08:08:08 EDT 2014
314 á645ñ Water Conductivity / Physical Tests USP 37

tion, and Sterile Water for Irrigation, and any other mono- to +150°, is available as the ASTM E1 series 89C through
graphs that specify this section. The sterile waters are de- 96C. Other temperature-measuring devices may be used if
rived from Purified Water or Water for Injection, and therefore they are validated for this procedure (see Thermometers
have been determined to be compliant with the Bulk Water á21ñ). Dimensions should be within ±20% of those given in
requirements before being stored in the container. The the illustration.
specification provided represents the maximum allowable
conductivity value, taking into consideration the limitation
of the measurement method and reasonable container
leaching. Such specification and the sampling volume
choices should be defined and validated on the basis of the
intended purpose of the water.

Procedure

Obtain a sample that suitably reflects the quality of water

used. Before opening, vigorously agitate the package to ho-
mogenize the water sample. Several packages may be re-
quired to collect sufficient water for analysis.
Transfer a sufficient amount of water to a suitable con-
tainer, and stir the test specimen. Adjust the temperature, if
General Chapters

necessary, and, while maintaining it at 25 ± 1°, begin vigo-

rously agitating the test specimen while periodically observ-
ing the conductivity. When the change in conductivity (due
to uptake of ambient carbon dioxide) is less than a net of
0.1 mS/cm per 5 min, note the conductivity.
For containers with a nominal volume of 10 mL or less, if
the conductivity is NMT 25 mS/cm, the water meets the re-
quirements. For containers with a nominal volume greater
than 10 mL, if the conductivity is NMT 5 mS/cm, the water
meets the requirements.

á651ñ CONGEALING
TEMPERATURE

The temperature at which a substance passes from the liq-

uid to the solid state upon cooling is a useful index to purity
if heat is liberated when the solidification takes place, provi-
ded that any impurities present dissolve in the liquid only,
and not in the solid. Pure substances have a well-defined
freezing point, but mixtures generally freeze over a range of
temperatures. For many mixtures, the congealing tempera-
ture, as determined by strict adherence to the following em-
pirical methods, is a useful index of purity. The method for
determining congealing temperatures set forth here is appli-
cable to substances that melt between −20° and 150°, the
range of the thermometer used in the bath. The congealing
temperature is the maximum point (or lacking a maximum,
the point of inflection) in the temperature-time curve.
Apparatus—Assemble an apparatus similar to that illus-
trated, in which the container for the substance is a 25- ×
100-mm test tube. This is provided with a suitable, short-
range thermometer suspended in the center, and a wire stir-
rer, about 30 cm long, bent at its lower end into a horizon-
tal loop around the thermometer. Use a thermometer hav-
ing a range not exceeding 30°, graduated in 0.1° divisions,
and calibrated for, but not used at, 76-mm immersion. A
suitable series of thermometers, covering a range from −20°
Congealing Temperature Apparatus
The specimen container is supported, by means of a cork,
in a suitable water-tight cylinder about 50 mm in internal
diameter and 11 cm in length. The cylinder, in turn, is sup-
ported in a suitable bath sufficient to provide not less than a
37-mm layer surrounding the sides and bottom of the cylin-
der. The outside bath is provided with a suitable thermome-
ter.
Procedure—Melt the substance, if a solid, at a tempera-
ture not exceeding 20° above its expected congealing
point, and pour it into the test tube to a height of 50 to 57
mm. Assemble the apparatus with the bulb of the test tube
thermometer immersed halfway between the top and bot-
tom of the specimen in the test tube. Fill the bath to about
12 mm from the top of the tube with suitable fluid at a tem-
perature 4° to 5° below the expected congealing point.
In case the substance is a liquid at room temperature, car-
ry out the determination using a bath temperature about
15° below the expected congealing point.
When the test specimen has cooled to about 5° above its
expected congealing point, adjust the bath to a tempera-

Official from August 1, 2014

Copyright (c) 2014 The United States Pharmacopeial Convention. All rights reserved.