Accessed from 80.28.157.

17 by quimica on Fri Aug 08 10:30:45 EDT 2014

310 á631ñ Color and Achromicity / Physical Tests USP 37

Matching Fluids (Continued) nologies from being used, but this chapter provides guid-
Parts of Parts of ance on how to qualify these analytical technologies for use
Match- Cobaltous Ferric Parts of as well as guidance on how to interpret instrument results
ing Chloride Chloride Cupric Parts of for use as a limit test.
Fluid CS CS Sulfate CS Water
Apparatuses commonly used to determine TOC in water
E 0.4 1.2 0.3 3.1
for pharmaceutical use have in common the objective of ox-
F 0.3 1.2 0.0 3.5 idizing the organic molecules in the water to produce car-
G 0.5 1.2 0.2 3.1 bon dioxide followed by the measurement of the amount of
H 0.2 1.5 0.0 3.3 carbon dioxide produced. Then the amount of CO2 pro-
I 0.4 2.2 0.1 2.3 duced is determined and used to calculate the organic car-
J 0.4 3.5 0.1 1.0 bon concentration in the water.
All technologies must discriminate between the inorganic
K 0.5 4.5 0.0 0.0
carbon, which may be present in the water from sources
L 0.8 3.8 0.1 0.3
such as dissolved CO2 and bicarbonate, and the CO2 gener-
M 0.1 2.0 0.1 2.8 ated from the oxidation of organic molecules in the sample.
N 0.0 4.9 0.1 0.0 The discrimination may be accomplished either by deter-
O 0.1 4.8 0.1 0.0 mining the inorganic carbon and subtracting it from the to-
P 0.2 0.4 0.1 4.3 tal carbon (total carbon is the sum of organic carbon and in-
Q 0.2 0.3 0.1 4.4 organic carbon), or by purging inorganic carbon from the
sample before oxidation. Although purging may entrain or-
R 0.3 0.4 0.2 4.1
General Chapters

ganic molecules, such purgeable organic carbon is present

S 0.2 0.1 0.0 4.7
in negligible quantities in water for pharmaceutical use.
T 0.5 0.5 0.4 3.6

BULK WATER

The following sections apply to tests for bulk Purified Wa-

á641ñ COMPLETENESS OF ter, Water for Injection, Water for Hemodialysis, and the con-
SOLUTION densate of Pure Steam.
Apparatus Requirements: This test method is performed
either as an on-line test or as an off-line laboratory test using
a calibrated instrument. The suitability of the apparatus
Place the quantity of the substance specified in the indi-
must be periodically demonstrated as described below. In
vidual monograph in a meticulously cleansed, glass-stop-
addition, it must have a manufacturer’s specified limit of de-
pered, 10-mL glass cylinder approximately 13 mm × 125
tection of 0.05 mg/L (0.05 ppm) or lower of carbon.
mm in size. Using the solvent that is specified in the mono-
When testing water for quality control purposes, ensure
graph or on the label of the product, fill the cylinder almost
that the instrument and its data are under appropriate con-
to the constriction at the neck. Shake gently to effect solu-
trol and that the sampling approaches and locations of both
tion: the solution is not less clear than an equal volume of
on-line and off-line measurements are representative of the
the same solvent contained in a similar vessel and examined
quality of the water used. The nature of the water produc-
similarly.
tion, distribution, and use should be considered when se-
lecting either on-line or off-line measurement.
USP Reference Standards á11ñ: USP 1,4-Benzoquinone
RS. USP Sucrose RS.
á643ñ TOTAL ORGANIC CARBON Reagent Water: Use water having a TOC level of not
more than 0.10 mg/L. [NOTE—A conductivity requirement
may be necessary in order to ensure method reliability.]
Total organic carbon (TOC) is an indirect measure of or- Container Preparation: Organic contamination of con-
ganic molecules present in pharmaceutical waters measured tainers results in higher TOC values. Therefore, use labware
as carbon. Organic molecules are introduced into the water and containers that have been scrupulously cleaned of or-
from the source water, from purification and distribution ganic residues. Any method that is effective in removing or-
system materials, from biofilm growing in the system, and ganic matter can be used (see Cleaning Glass Apparatus
from the packaging of sterile and nonsterile waters. TOC á1051ñ). Use Reagent Water for the final rinse.
can also be used as a process control attribute to monitor Standard Solution: Unless otherwise directed in the indi-
the performance of unit operations comprising the purifica- vidual monograph, dissolve in the Reagent Water an accu-
tion and distribution system. A TOC measurement is not a rately weighed quantity of USP Sucrose RS to obtain a solu-
replacement test for endotoxin or microbiological control. tion having a concentration of 1.19 mg/L of sucrose (0.50
Although there can be a qualitative relationship between a mg/L of carbon).
food source (TOC) and microbiological activity, there is no System Suitability Solution: Dissolve in Reagent Water an
direct numerical correlation. accurately weighed quantity of USP 1,4-Benzoquinone RS to
A number of acceptable methods exist for analyzing TOC. obtain a solution having a concentration of 0.75 mg/L (0.50
This chapter does not endorse, limit, or prevent any tech- mg/L of carbon).

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 10:30:45 EDT 2014
USP 37 Physical Tests / á645ñ Water Conductivity 311

Reagent Water Control: Use a suitable quantity of Re- Water Sample: Obtain a sample that suitably reflects
agent Water obtained at the same time as that used in the the quality of water used. Before opening, vigorously agitate
preparation of the Standard Solution and the System Suitabili- the package to homogenize the water sample. Several pack-
ty Solution. ages may be required in order to collect sufficient water for
Water Sample: Obtain an on-line or off-line sample that analysis.
suitably reflects the quality of water used. System Suitability: Test the Reagent Water Control in
Other Control Solutions: Prepare appropriate reagent the apparatus, and record the response, rW. Repeat the test
blank solutions or other specified solutions needed for estab- using the Standard Solution, and record the response, rS. Cal-
lishing the apparatus baseline or for calibration adjustments culate the corrected Standard Solution response, which is al-
following the manufacturer’s instructions, and run the ap- so the limit response, by subtracting the Reagent Water Con-
propriate blanks to zero the instrument, if necessary. trol response from the response of the Standard Solution.
System Suitability: Test the Reagent Water Control in the The theoretical limit of 8.0 mg/L of carbon is equal to the
apparatus, and record the response, rW. Repeat the test us- corrected Standard Solution response, rS − rW. Test the System
ing the Standard Solution, and record the response, rS. Cal- Suitability Solution in the apparatus, and record the re-
culate the corrected Standard Solution response, which is al- sponse, rSS. Calculate the corrected System Suitability Solution
so the limit response, by subtracting the Reagent Water Con- response by subtracting the Reagent Water Control response
trol response from the response of the Standard Solution. from the response of the System Suitability Solution, rSS − rW.
The theoretical limit of 0.50 mg/L of carbon is equal to the Calculate the percent response efficiency for the System Suit-
corrected Standard Solution response, rS − rW. Test the System ability Solution:
Suitability Solution in the apparatus, and record the re-
% response efficiency = 100[(rSS − rW)/(rS − rW)]

General Chapters
sponse, rSS. Calculate the corrected System Suitability Solution
response by subtracting the Reagent Water Control response where rSS is the instrument response to the System Suitability
from the response of the System Suitability Solution, rSS − rW. Solution; rW is the instrument response to the Reagent Water
Calculate the percent response efficiency for the System Suit- Control; and rS is the instrument response to the Standard
ability Solution: Solution. The system is suitable if the percent response effi-
% response efficiency = 100[(rSS − rW)/(rS − rW)] ciency is not less than 85% and not more than 115%.
Procedure: Perform the test on the Water Sample, and
where rSS is the instrument response to the System Suitability record the response, rU. The Water Sample meets the re-
Solution; rW is the instrument response to the Reagent Water quirements if rU is not more than the limit response, rS − rW,
Control; and rS is the instrument response to the Standard determined in the System Suitability requirements in Sterile
Solution. The system is suitable if the percent response effi- Water.
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 á645ñ WATER CONDUCTIVITY
method can be performed using on-line or off-line instru-
mentation that meets the Apparatus Requirements.
Change to read:
STERILE WATER
s INTRODUCTIONsUSP37
The following sections apply to tests for Sterile Water for
Injection, Sterile Purified Water, Sterile Water for Irrigation, and
Electrical conductivity in water is a measure of the ion-fa-
Sterile Water for Inhalation.
cilitated electron flow through it. Water molecules dissociate
Follow the requirements in Bulk Water, with the following
into ions as a function of pH and temperature and result in a
exceptions.
very predictable conductivity. Some gases, most notably
Apparatus Requirements: In addition to the Apparatus
carbon dioxide, readily dissolve in water and interact to
Requirements in Bulk Water, the apparatus must have a man-
form ions, which predictably affect conductivity salso.sUSP37
ufacturer’s specified limit of detection of 0.10 mg/L (0.10
For the purpose of this discussion, these ions and their re-
ppm) or lower of carbon.
sulting conductivity can be considered intrinsic to the water.
Reagent Water: Use water having a TOC level of not sWater conductivity is also affected by the presence of ex-
more than 0.50 mg/L. [NOTE—A conductivity requirement
traneous ions. The extraneous ions used in modeling the
may be necessary in order to ensure method reliability.]
conductivity specifications described below are the chloride
Standard Solution: Unless otherwise directed in the in-
and ammonia ions. The conductivity of the ubiquitous
dividual monograph, dissolve in the Reagent Water an accu-
chloride ion (at the theoretical endpoint concentration of
rately weighed quantity of USP Sucrose RS to obtain a solu-
0.47 ppm when chloride was a required attribute test in USP
tion having a concentration of 19.0 mg/L of sucrose (8.0
22 and earlier revisions) and the ammonium ion (at the limit
mg/L of carbon).
of 0.3 ppm) represents a major portion of the allowed water
System Suitability Solution: Dissolve in Reagent Water
ionic impurity level. A balancing quantity of anions (such as
an accurately weighed quantity of USP 1,4-Benzoquinone
chloride, to counter the ammonium ion) and cations (such
RS to obtain a solution having a concentration of 12.0 mg/L
as sodium, to counter the chloride ion) is included in this al-
(8.0 mg/L of carbon).

Official from August 1, 2014

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