JP XVII Official Monographs / Purified Water 1773

lution T1 and the solution S1 at 272 nm as directed under solution, discard the first 10 mL of the filtrate, and use the
Ultraviolet-visible Spectrophotometry <2.24>, using the solu- subsequent filtrate as the sample solution. Separately, weigh
tion T2 and the solution S2 as the blank, respectively. accurately about 80 mg of Warfarin Potassium RS, previ-
ously dried at 1059C for 3 hours, and dissolve in water to
Amount (mg) of warfarin potassium (C19H15KO4)
make exactly 100 mL. Pipet 5 mL of this solution, add water
＝ MS × AT/AS × V/2000
to make exactly 100 mL, and use this solution as the stand-
MS: Amount (mg) of Warfarin Potassium RS taken ard solution. Pipet 10 mL each of the sample solution and
standard solution, add 0.02 mol/L hydrochloric acid TS to
Dissolution <6.10> When the test is performed at 50 revolu-
make exactly 20 mL, and use these solutions as the solution
tions per minute according to the Paddle method, using 900
T1 and the solution S1, respectively. Separately, pipet 10 mL
mL of water as the dissolution medium, the dissolution rates
each of the sample solution and standard solution, add 0.02
in 15 minutes of 0.5-mg, 1-mg and 2-mg tablet and in 30
mol/L potassium hydroxide TS to make exactly 20 mL, and
minutes of 5-mg tablet of Warfarin Potassium Tablets are
use these solutions as the solution T2 and the solution S2,
not less than 80z.
respectively. Determine the absorbances, AT and AS, of the
Start the test with 1 tablet of Warfarin Potassium Tablets,
solution T1 and the solution S1 at 272 nm as directed under
withdraw not less than 20 mL of the medium at the specified
Ultraviolet-visible Spectrophotometry <2.24>, using the solu-
minute after starting the test, and filter through a membrane
tion T2 and the solution S2 as the blank, respectively.
filter with a pore size not exceeding 0.45 mm. Discard the
first 10 mL of the filtrate, pipet V mL of the subsequent Amount (mg) of warfarin potassium (C19H15KO4)
filtrate, add water to make exactly V? mL so that each mL ＝ MS × AT/AS × 1/20
contains about 0.56 mg of warfarin potassium (C19H15KO4),
MS: Amount (mg) of Warfarin Potassium RS taken
and use this solution as the sample solution. Separately,
weigh accurately about 22 mg of Warfarin Potassium RS, Containers and storage Containers—Tight containers.
previously dried at 1059C for 3 hours, and dissolve in water Storage—Light-resistant.
to make exactly 100 mL. Pipet 5 mL of this solution, and
add water to make exactly 100 mL. Pipet 5 mL of this solu-
tion, add water to make exactly 100 mL, and use this solu- Water
tion as the standard solution. Perform the test with exactly
100 mL each of the sample solution and standard solution as 常水
directed under Liquid Chromatography <2.01> according to
the following conditions, and determine the peak areas, AT
H2O: 18.02
and AS, of warfarin in each solution.
Dissolution rate (z) with respect to the labeled amount Water must meet the Quality Standards of Drinking
of warfarin potassium (C19H15KO4) water provided under the Article 4 of the Water
＝ MS × AT/AS × V?/V × 1/C × 9/4 Supply Law (the Ministry of Health, Labour and Wel-
fare Ministerial Ordinance No.101, 2003). In the case
MS: Amount (mg) of Warfarin Potassium RS taken
that Water is prepared at individual facilities using
C: Labeled amount (mg) of warfarin potassium
well water or industrial water as source water, it must
(C19H15KO4) in 1 tablet
meet the following additional requirement as well as
Operating conditions— the Quality Standards of Drinking water.
Detector: An ultraviolet absorption photometer (wave-
Purity Ammonium <1.02>—Perform the test with 30 mL of
length: 283 nm).
Water as directed under Ammonium Limit Test. Prepare the
Column: A stainless steel column 4.6 mm in inside diame-
control solution as follows: to 0.15 mL of Standard Ammo-
ter and 15 cm in length, packed with octadecylsilanized silica
nium Solution add water for ammonium limit test to make
gel for liquid chromatography (5 mm in particle diameter).
30 mL (not more than 0.05 mg/L).
Column temperature: A constant temperature of about
359 C.
Mobile phase: A mixture of methanol, water and phos-
phoric acid (700:300:1). Purified Water
Flow rate: Adjust so that the retention time of warfarin is
精製水
about 6 minutes.
System suitability—
System performance: When the procedure is run with 100 Purified Water is prepared from Water by ion-
mL of the standard solution under the above conditions, the exchange, distillation, reverse osmosis or ultrafiltra-
number of theoretical plates and the symmetry factor of the tion, or by a combination of these processes.
peak of warfarin are not less than 2000 and not more than It must be used immediately after preparation.
2.0, respectively. However, it may be stored temporarily, if adequate
System repeatability: When the test is repeated 6 times countermeasures for preventing microbial prolifera-
with 100 mL of the standard solution under the above operat- tion are taken.
ing conditions, the relative standard deviation of the peak
Description Purified Water is a clear and colorless liquid,
area of warfarin is not more than 2.0z.
having no odor.
Assay Weigh accurately and powder not less than 20
Purity Total organic carbon <2.59>—Not more than 0.50
Warfarin Potassium Tablets. Weigh accurately a portion of
mg/L.
the powder, equivalent to about 4 mg of warfarin potassium
(C19H15KO4), add 80 mL of water, shake vigorously for 15 Conductivity <2.51> When the test is performed according
minutes, and add water to make exactly 100 mL. Filter this to the following method, the conductivity (259C) is not more

The JP Drugs are to be tested according to the provisions given in the pertinent monographs, General Notices, General Rules for Crude Drugs,
General Rules for Preparations, and General Tests for their conformity to the Japanese Pharmacopoeia. (See the General Notices 5.)
1774 Purified Water in Containers / Official Monographs
than 2.1 mS・cm－1.
Transfer a suitable amount of Purified Water to a beaker,
and stir the water specimen. Adjust the temperature to 25 ±
19C, and begin agitating the water specimen vigorously,
while observing its conductivity periodically. When the
change in conductivity becomes not greater than 0.1 mS・
cm－1 per 5 minutes, adopt the observed value as the conduc-
tivity of the water specimen.
Purified Water in Containers
精製水（容器入り）
Purified Water in Containers is prepared from Puri-
fied Water by introducing it in a tight container.
It is allowable to describe it as ``Purified Water'' on
the label.
Description Purified Water in Containers is a clear and
colorless liquid, having no odor.
Purity Potassium permanganate-reducing substances—To
100 mL of Purified Water in Containers add 10 mL of dilute
sulfuric acid, boil, then add 0.10 mL of 0.02 mol/L potas-
sium permanganate VS, and boil again for 10 minutes: the
red color of the solution does not disappear.
Conductivity <2.51> When the test is performed according
to the following method, the conductivity (259C) is not more
than 25 mS・cm－1 for containers with a nominal volume of 10
mL or less, and not more than 5 mS・cm－1 for containers
with a nominal volume greater than 10 mL.
Transfer a suitable amount of Purified Water in Contain-
ers to a beaker, and stir the water specimen. Adjust the
temperature to 25 ± 19C, and begin agitating the water
specimen vigorously, while observing its conductivity
periodically. When the change in conductivity becomes not
greater than 0.1 mS・cm－1 per 5 minutes, adopt the observed
value as the conductivity of the water specimen.
Microbial limit <4.05> The acceptance criteria of TAMC is
102 CFU/mL. Perform the test using soybean-casein digest
agar medium.
Containers and storage Containers—Tight containers.
Sterile Purified Water in Containers
滅菌精製水（容器入り）
Sterile Purified Water in Containers is prepared
from Purified Water by introducing it into a hermetic
container, sealing up the container, then sterilizing the
product, or by making it sterile using a suitable
method, introducing the sterilized water into a sterile
hermetic container by applying aseptic manipulation,
then sealing up the container.
Description Sterile Purified Water in Containers is a clear
and colorless liquid, having no odor.
Purity Potassium permanganate-reducing substances—To
100 mL of Sterile Purified Water in Containers add 10 mL
of dilute sulfuric acid, boil, then add 0.10 mL of 0.02 mol/L
potassium permanganate VS, and boil again for 10 minutes:
the red color of the solution does not disappear.
Conductivity <2.51> When the test is performed according
JP XVII
to the following method, the conductivity (259C) is not more
than 25 mS・cm－1 for containers with a nominal volume of 10
mL or less, and not more than 5 mS・cm－1 for containers
with a nominal volume greater than 10 mL.
Transfer a suitable amount of Sterile Purified Water in
Containers to a beaker, and stir the water specimen. Adjust
the temperature to 25 ± 19C, and begin agitating the water
specimen vigorously, while observing its conductivity period-
ically. When the change in conductivity becomes not greater
than 0.1 mS・cm－1 per 5 minutes, adopt the observed value as
the conductivity of the water specimen.
Sterility <4.06> It meets the requirements.
Containers and storage Containers—Hermetic containers.
Plastic containers for aqueous injections can be used in place
of hermetic containers.
Water for Injection
注射用水
Water for Injection is prepared by distillation or by
reverse osmosis and/or ultrafiltration, either: from the
water which is obtained by appropriate pretreatments
such as ion-exchange or reverse osmosis on Water: or
from Purified Water.
When Water for Injection is prepared by the reverse
osmosis and/or ultrafiltration (methods for refining
water by using a reverse osmosis membrane module,
an ultrafiltration membrane module capable of remov-
ing substances having molecular masses of 6,000 and
above, or a module using both types of membranes),
care must be taken to avoid microbial contamination
of the water processing system, and to provide water
with equivalent quality to that prepared by distillation
consistently.
Water for Injection must be used immediately after
preparation. However, it may be stored temporarily, if
adequate countermeasures able to prevent microbial
proliferation stringently, such as circulating it in a
loop at a high temperature, are established.
Description Water for Injection is a clear and colorless
liquid, having no odor.
Purity Total organic carbon <2.59>—Not more than 0.50
mg/L.
Conductivity <2.51> When the test is performed according
to the following method, the conductivity (259C) is not more
than 2.1 mS・cm－1.
Transfer a suitable amount of Water for Injection to a
beaker, and stir the water specimen. Adjust the temperature
to 25 ± 19C, and begin agitating the water specimen
vigorously, while observing its conductivity periodically.
When the change in conductivity becomes not greater than
0.1 mS・cm－1 per 5 minutes, adopt the observed value as the
conductivity of the water specimen.
Bacterial endotoxins <4.01> Less than 0.25 EU/mL.

The JP Drugs are to be tested according to the provisions given in the pertinent monographs, General Notices, General Rules for Crude Drugs,
General Rules for Preparations, and General Tests for their conformity to the Japanese Pharmacopoeia. (See the General Notices 5.)