942 Fluconazole Injection / Official Monographs JP XVII

Dissolution rate (z) with respect to the labeled amount ing conditions, the relative standard deviation of the peak
of fluconazole (C13H12F2N6O) area of fluconazole is not more than 1.0z.
＝ MS × AT/AS × V?/V × 1/C × 90
Containers and storage Containers—Tight containers.
MS: Amount (mg) of fluconazole for assay taken
C: Labeled amount (mg) of fluconazole (C13H12F2N6O) in
1 capsule Fluconazole Injection
Operating conditions—
フルコナゾール注射液
Proceed as directed in the operating conditions in the
Assay.
System suitability— Fluconazole Injection is an aqueous injection.
System performance: When the procedure is run with 20 It contains not less than 95.0z and not more
mL of the standard solution under the above operating con- than 105.0z of the labeled amount of fluconazole
ditions, the number of theoretical plates and the symmetry (C13H12F2N6O: 306.27).
factor of the peak of fluconazole are not less than 3000 and
Method of preparation Prepare as directed under Injec-
not more than 1.5, respectively.
tions, with Fluconazole.
System repeatability: When the test is repeated 6 times
with 20 mL of the standard solution under the above operat- Description Fluconazole Injection occurs as a clear and
ing conditions, the relative standard deviation of the peak colorless liquid.
area of fluconazole is not more than 1.0z.
Identification (1) Take a volume of Fluconazole Injec-
Assay Take out the contents from not less than 20 tion, equivalent to 0.1 g of Fluconazole, and evaporate to
Fluconazole Capsules, weigh accurately, and powder, if dryness on a water bath. To the residue add 10 mL of dilute
necessary. Weigh accurately a quantity of the contents, hydrochloric acid, shake, and filter. Add 1 mL of Reinecke
equivalent to about 50 mg of fluconazole (C13H12F2N6O), salt TS to the filtrate: a light red precipitate is produced.
and add the mobile phase to make exactly 100 mL. Disperse (2) Determine the absorption spectrum of the sample
the particles with the aid of ultrasonic waves, stir for 30 solution obtained in the Assay as directed under Ultraviolet-
minutes, and filter through a membrane filter with a pore visible Spectrophotometry <2.24>: it exhibits maxima be-
size not exceeding 0.45 mm. Discard the first 10 mL of the fil- tween 259 nm and 263 nm, and between 264 nm and 268 nm.
trate, pipet 5 mL of the subsequent filtrate, add the mobile
pH Being specified separately when the drug is granted ap-
phase to make exactly 50 mL, and use this solution as the
proval based on the Law.
sample solution. Separately, weigh accurately about 25 mg
of fluconazole for assay, previously dried at 1059C for 4 Bacterial endotoxins <4.01> Less than 0.75 EU/mg.
hours, and dissolve in the mobile phase to make exactly 50
Extractable volume <6.05> It meets the requirement.
mL. Pipet 5 mL of this solution, add the mobile phase to
make exactly 50 mL, and use this solution as the standard Foreign insoluble matter <6.06> Perform the test according
solution. Perform the test with exactly 20 mL each of the to Method 1: it meets the requirement.
sample solution and standard solution as directed under
Insoluble particulate matter <6.07> It meets the require-
Liquid Chromatography <2.01> according to the following
ment.
conditions, and determine the peak areas, AT and AS, of
fluconazole in each solution. Sterility <4.06> Perform the test according to the Mem-
brane filtration method: it meets the requirement.
Amount (mg) of fluconazole (C13H12F2N6O)
＝ M S × AT / AS × 2 Assay Pipet a volume of Fluconazole Injection, equivalent
to 10 mg of fluconazole (C13H12F2N6O), add water to make
MS: Amount (mg) of fluconazole for assay taken
exactly 50 mL, and use this solution as the sample solution.
Operating conditions— Separately, weigh accurately about 50 mg of fluconazole for
Detector: An ultraviolet absorption photometer (wave- assay, previously dried at 1059C for 4 hours, dissolve in a so-
length: 261 nm). lution of sodium chloride (9 in 1000) to make exactly 50 mL.
Column: A stainless steel column 3.9 mm in inside diame- Pipet 10 mL of this solution, add water to make exactly 50
ter and 15 cm in length, packed with octadecylsilanized silica mL, and use this solution as the standard solution. Deter-
gel for liquid chromatography (4 mm in particle diameter). mine the absorbances, AT and AS, of the sample solution
Column temperature: A constant temperature of about and standard solution at 261 nm as directed under Ultravio-
359 C. let-visible Spectrophotometry <2.24>.
Mobile phase: Dissolve 0.82 g of anhydrous sodium ace-
Amount (mg) of fluconazole (C13H12F2N6O)
tate in 1000 mL of water, and adjust to pH 5.0 with acetic
＝ MS × AT/AS × 1/5
acid (100). To 700 mL of this solution add 200 mL of metha-
nol and 100 mL of acetonitrile. MS: Amount (mg) of fluconazole for assay taken
Flow rate: Adjust so that the retention time of fluconazole
Containers and storage Containers—Hermetic containers.
is about 4 minutes.
System suitability—
System performance: When the procedure is run with 20
mL of the standard solution under the above operating con-
ditions, the number of theoretical plates and the symmetry
factor of the peak of fluconazole are not less than 3000 and
not more than 1.5, respectively.
System repeatability: When the test is repeated 6 times
with 20 mL of the standard solution under the above operat-
JP XVII Official Monographs / Flucytosine 943

as the standard solution. Transfer 5.0 mL of diluted 0.01

Flucytosine mol/L sodium hydroxide TS (1 in 20) to a 20-mL volumetric
flask, proceed in the same manner as directed in the prepara-
フルシトシン tion of the standard solution, and use this solution as the
blank solution. Determine the absorbances, AT and AS, of
the sample solution and standard solution at 600 nm, using
the blank solution as the control as directed under Ultravio-
let-visible Spectrophotometry <2.24>: AT is not larger than
AS (not more than 0.048z).
(4) Heavy metals <1.07>—Proceed with 1.0 g of Flucyto-
C4H4FN3O: 129.09
sine according to Method 2, and perform the test. Prepare
5-Fluorocytosine
the control solution with 2.0 mL of Standard Lead Solution
[2022-85-7]
(not more than 20 ppm).
(5) Arsenic <1.11>—Prepare the test solution with 1.0 g
Flucytosine, when dried, contains not less than
of Flucytosine according to Method 2, and perform the test
98.5z of flucytosine (C4H4FN3O), and not less than
(not more than 2 ppm).
14.0z and not more than 15.5z of fluorine (F:
(6) Related substances—Dissolve 50 mg of Flucytosine in
19.00).
5 mL of diluted methanol (1 in 2), and use this solution as
Description Flucytosine occurs as a white crystalline pow- the sample solution. Measure accurately 1 mL of the sample
der. It is odorless. solution, add diluted methanol (1 in 2) to make exactly 25
It is sparingly soluble in water, slightly soluble in metha- mL. Measure accurately 1 mL of this solution, add diluted
nol, in ethanol (95), in acetic anhydride and in acetic acid methanol (1 in 2) to make exactly 20 mL, and use this solu-
(100), and practically insoluble in diethyl ether. tion as the standard solution. Perform the test with these so-
It dissolves in 0.1 mol/L hydrochloric acid TS. lutions as directed under Thin-layer Chromatography <2.03>.
The pH of a solution of 1.0 g of Flucytosine in 100 mL of Spot 20 mL each of the sample solution and standard solu-
water is between 5.5 and 7.5. tion on a plate of silica gel with fluorescent indicator for
It is slightly hygroscopic. thin-layer chromatography. Develop the plate with a mixture
Melting point: about 2959C (with decomposition). of ethyl acetate, methanol and water (5:3:2) to a distance of
about 12 cm, air-dry the plate, and observe the spots under
Identification (1) Add 0.2 mL of bromine TS to 5 mL of
ultraviolet light (main wavelength: 254 nm): the spots other
a solution of Flucytosine (1 in 500): a yellow-brown color of
than the principal spot from the sample solution are not
bromine TS is immediately discharged. Further add 2 mL of
more intense than the spot from the standard solution.
barium hydroxide TS: a purple precipitate is formed.
(2) Proceed with 0.1 g of Flucytosine as directed under Loss on drying <2.41> Not more than 1.0z (1 g, 1059C,
Oxygen Flask Combustion Method <1.06>, using a mixture 4 hours).
of 0.5 mL of 0.01 mol/L sodium hydroxide TS and 20 mL of
Residue on ignition <2.44> Not more than 0.1z (1 g).
water as the absorbing liquid. The solution responds to the
Qualitative Tests <1.09> (2) for fluoride. Assay (1) Flucytosine—Weigh accurately about 0.2 g of
(3) Determine the absorption spectrum of a solution of Flucytosine, previously dried, dissolve in 40 mL of acetic
Flucytosine in 0.1 mol/L hydrochloric acid TS (1 in 125,000) acid (100), add 100 mL of acetic anhydride, and titrate
as directed under Ultraviolet-visible Spectrophotometry <2.50> with 0.1 mol/L perchloric acid VS (potentiometric
<2.24>, and compare the spectrum with the Reference Spec- titration). Perform a blank determination.
trum: both spectra exhibit similar intensities of absorption at
Each mL of 0.1 mol/L perchloric acid VS
the same wavelengths.
＝ 12.91 mg of C4H4FN3O
Purity (1) Clarity and color of solution—Dissolve 1.0 g
(2) Fluorine—Weigh accurately about 10 mg of Flucyto-
of Flucytosine in 100 mL of water: the solution is clear and
sine, previously dried, and proceed as directed in the deter-
colorless.
mination of fluorine under Oxygen Flask Combustion
(2) Chloride <1.03>—Dissolve 1.0 g of Flucytosine in 80
Method <1.06>, using a mixture of 0.5 mL of 0.01 mol/L
mL of water by heating on a water bath. After cooling, to 40
sodium hydroxide VS and 20 mL of water as the absorbing
mL of this solution add 6 mL of dilute nitric acid and water
liquid.
to make 50 mL. Perform the test using this solution as the
test solution. Prepare the control solution with 0.20 mL of Containers and storage Containers—Tight containers.
0.01 mol/L hydrochloric acid VS (not more than 0.014z). Storage—Light-resistant.
(3) Fluoride—Dissolve 0.10 g of Flucytosine in 10.0 mL
of diluted 0.01 mol/L sodium hydroxide TS (1 in 20). Trans-
fer 5.0 mL of this solution to a 20-mL volumetric flask, add
10 mL of a mixture of alizarin complexone TS, acetic acid-
potassium acetate buffer solution (pH 4.3) and cerrous ni-
trate TS (1:1:1), and add water to make 20 mL. Allow the
mixture to stand for 1 hour, and use this solution as the sam-
ple solution. Separately, transfer 4.0 mL of Standard Fluo-
rine Solution to a 20-mL volumetric flask, add 5.0 mL of
diluted 0.01 mol/L sodium hydroxide TS (1 in 20), add 10
mL of a mixture of alizarin complexone TS, acetic acid-
potassium acetate buffer solution (pH 4.3) and cerrous ni-
trate TS (1:1:1). Proceed in the same manner as directed in
the preparation of the sample solution, and use this solution