Printed on: Fri Jan 05 2024, 08:57:41 PM(EST) Status: Currently Official on 06-Jan-2024 DocId: GUID-4091C7E0-92EA-46DA-8B0E-A2D928D42AAB_4_en-US

Printed by: USP NF Official Date: Official as of 01-May-2020 Document Type: USP @2024 USPC
Do Not Distribute DOI Ref: cat5p DOI: https://doi.org/10.31003/USPNF_M350_04_01
1

CS = concentration of USP Acetazolamide RS in the

Acetazolamide for Injection Standard solution (mg/mL)
DEFINITION CU = nominal concentration of acetazolamide in the
Acetazolamide for Injection is prepared from Acetazolamide Sample solution (mg/mL)
with the aid of sodium hydroxide. It is suitable for parenteral
Acceptance criteria: 95.0%–110.0%
use. The contents of each container, when constituted as
directed in the labeling, yield a solution containing NLT PERFORMANCE TESTS
95.0% and NMT 110.0% of the labeled amount of • UNIFORMITY OF DOSAGE UNITS á905ñ: Meets the
acetazolamide (C4H6N4O3S2). requirements
IDENTIFICATION IMPURITIES
• ORGANIC IMPURITIES
Change to read: Buffer: 6.8 g/L of monobasic potassium phosphate in water
• A. ▲SPECTROSCOPIC IDENTIFICATION TESTS á197ñ, Infrared Mobile phase: Acetonitrile and Buffer (10:90)
Spectroscopy: 197K▲ (CN 1-May-2020) System suitability solution: 0.16 µg/mL each of USP
Sample: Dissolve 500 mg in 5 mL of water, add 2 drops of Acetazolamide Related Compound D RS and USP
hydrochloric acid, and allow the mixture to stand for about Acetazolamide Related Compound E RS in Mobile phase
15 min. Filter through a fine sintered-glass funnel, wash Standard stock solution: 0.1 mg/mL of USP
with several small portions of water, and dry under vacuum Acetazolamide RS prepared as follows. Transfer a weighed
over silica gel for 3 h. amount of USP Acetazolamide RS to a suitable volumetric
Acceptance criteria: Meets the requirements flask and add acetonitrile equivalent to 10% of the final
• B. The retention time of the major peak of the Sample volume and Buffer equivalent to 20% of the final volume.

al
solution corresponds to that of the Standard solution, as Sonicate to dissolve and dilute with Buffer to volume.
obtained in the Assay. Standard solution: 0.8 µg/mL of USP Acetazolamide RS
• C. IDENTIFICATION TESTS—GENERAL á191ñ, Chemical from Standard stock solution in Mobile phase
Identification Tests, Sodium: Meets the requirements Sample solution: Nominally 0.4 mg/mL of acetazolamide
from Acetazolamide for Injection prepared as follows.
ASSAY Dissolve the contents of one container of Acetazolamide for
• PROCEDURE
Mobile phase: Dissolve 4.1 g of anhydrous sodium acetate
in 950 mL of water, add 20 mL of methanol and 30 mL of
ci Injection in water corresponding to the volume of solvent
specified in the labeling. Dilute with Mobile phase as
needed.
acetonitrile, and mix. Adjust with glacial acetic acid to a pH Chromatographic system
of 4.0. (See Chromatography á621ñ, System Suitability.)
ffi
Standard solution: 0.1 mg/mL of USP Acetazolamide RS Mode: LC
prepared as follows. Transfer USP Acetazolamide RS to a Detector: 265 nm
suitable volumetric flask, add 0.5 N sodium hydroxide Column: 4.6-mm × 15-cm; 3.5-µm packing L11
equivalent to 10% of the final volume, and dilute with water Flow rate: 1.0 mL/min
to volume. Injection volume: 25 µL
Sample solution: Nominally 0.1 mg/mL of acetazolamide Run time: NLT 3.5 times the retention time of
O

from Acetazolamide for Injection prepared as follows. acetazolamide

Dissolve the contents of one container of Acetazolamide for System suitability
Injection in a volume of water corresponding to the volume Samples: System suitability solution and Standard solution
of solvent specified in the labeling. Dilute with water as Suitability requirements
needed. Resolution: NLT 1.5 between acetazolamide related
Chromatographic system compound E and acetazolamide related compound D,
(See Chromatography á621ñ, System Suitability.) System suitability solution
Mode: LC Relative standard deviation: NMT 5.0%, Standard
Detector: UV 254 nm solution
Column: 4.6-mm × 25-cm; 10-µm packing L1 Analysis
Flow rate: 2 mL/min Samples: Standard solution and Sample solution
Injection volume: 20 µL Calculate the percentage of each impurity in the portion of
System suitability Acetazolamide for Injection taken:
Sample: Standard solution
Suitability requirements Result = (r U/r S) × (C S/C U) × (1/F) × 100
Tailing factor: NMT 1.5
Relative standard deviation: NMT 1.0% rU = peak area of each impurity from the Sample
Analysis solution
Samples: Standard solution and Sample solution rS = peak area of acetazolamide from the Standard
Calculate the percentage of the labeled amount of solution
acetazolamide (C4H6N4O3S2) in the portion of CS = concentration of USP Acetazolamide RS in the
Acetazolamide for Injection taken: Standard solution (mg/mL)
CU = nominal concentration of acetazolamide in the
Result = (r U/r S) × (C S/C U) × 100 Sample solution (mg/mL)
F = relative response factor (see Table 1)
rU = peak response of acetazolamide from the
Sample solution Acceptance criteria: See Table 1. Disregard any impurity
rS = peak response of acetazolamide from the peak less than 0.05%.
Standard solution

https://online.uspnf.com/uspnf/document/1_GUID-4091C7E0-92EA-46DA-8B0E-A2D928D42AAB_4_en-US 1/2
Printed on: Fri Jan 05 2024, 08:57:41 PM(EST) Status: Currently Official on 06-Jan-2024 DocId: GUID-4091C7E0-92EA-46DA-8B0E-A2D928D42AAB_4_en-US
Printed by: USP NF Official Date: Official as of 01-May-2020 Document Type: USP @2024 USPC
Do Not Distribute DOI Ref: cat5p DOI: https://doi.org/10.31003/USPNF_M350_04_01
2

Table 1 f N,N′-{5,5′-[(Hydrosulfonylamino)sulfonyl]bis(1,3,4-thiadiazole-5,2-diyl)}
diacetamide.
Relative Relative Acceptance
Retention Response Criteria,
Name Time Factor NMT (%) SPECIFIC TESTS
Acetazolamide
• PH á791ñ
related compound Ea 0.38
— — Sample solution: Freshly prepared solution (1 in 10)
Acceptance criteria: 9.0–10.0
Acetazolamide • BACTERIAL ENDOTOXINS TEST á85ñ: It contains NMT 0.5 USP
related compound D 0.43 0.70 2.0
Endotoxin Units/mg of acetazolamide.
Aminothiadiazole
— —
• INJECTIONS AND IMPLANTED DRUG PRODUCTS á1ñ, Product
mercaptana, b 0.55 Quality Tests Common to Parenteral Dosage Forms, Specific
Acetamidothiadiazolea, c 0.77 — — Tests, Completeness and Clarity of Solutions: Meets the
requirements at the time of use
Acetazolamide 1.0 — — • STERILITY TESTS á71ñ: Meets the requirements
Mercaptothiadiazole ana- ADDITIONAL REQUIREMENTS
— —
loga, d 1.4
• PACKAGING AND STORAGE: Preserve as described in
Chlorothiadiazole
— —
Packaging and Storage Requirements á659ñ, Injection
analoga, e 2.2 Packaging, Packaging for constitution, preferably in
Acetazolamide dimera, f 2.8 — — containers of Type III glass, and store at room temperature.
• LABELING á7ñ, Labels and Labeling for Injectable Products:
Any unspecified Meets the requirements
—
degradation product 1.0 0.20
• USP REFERENCE STANDARDS á11ñ

al
Total degradation products — — 3.0 USP Acetazolamide RS
USP Acetazolamide Related Compound D RS
a This process impurity is controlled in the drug substance. It is included in the
5-Amino-1,3,4-thiadiazole-2-sulfonamide.
table for identification only and is not to be reported in the total degradation
products.
C2H4N4O2S2 180.21
b 5-Amino-1,3,4-thiadiazole-2-thiol. ci USP Acetazolamide Related Compound E RS
c N-(1,3,4-Thiadiazol-2-yl)acetamide. 5-Acetamido-1,3,4-thiadiazole-2-sulfonic acid potassium
d N-(5-Mercapto-1,3,4-thiadiazol-2-yl)acetamide. salt.
e N-(5-Chloro-1,3,4-thiadiazol-2-yl)acetamide. C4H4KN3O4S2 261.32
ffi
O

https://online.uspnf.com/uspnf/document/1_GUID-4091C7E0-92EA-46DA-8B0E-A2D928D42AAB_4_en-US 2/2