Atropine Sulfate

This article is compiled based on the United States Pharmacopeia (USP) – 2025 Edition

Issued and maintained by the United States Pharmacopeial Convention (USP)

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Atropine Sulfate

Change to read:

(C₁₇H₂₃NO₃)₂·H₂SO₄·H₂O ▲694.84▲ (ERR 1-Jul-2020)

Anhydrous 676.82

Benzeneacetic acid, α-(hydroxymethyl)-, 8-methyl-8-azabicyclo[3.2.1]oct-3-yl ester, endo-(±)-, sulfate (2:1) (salt), monohydrate;

1αH,5αH-Tropan-3-α-ol (±)-tropate (ester), sulfate (2:1) (salt) monohydrate

CAS RN®: 5908-99-6; UNII: 03J5ZE7KA5.

Anhydrous CAS RN®: 55-48-1; UNII: KAE4PSB0Z3.

1 DEFINITION

Atropine Sulfate contains NLT 98.0% and NMT 102.0% of atropine sulfate (C₁₇H₂₃NO₃)₂·H₂SO₄ calculated on the anhydrous basis.

[Caution—Handle atropine sulfate with exceptional care, because it is highly potent.]

2 IDENTIFICATION

A. Spectroscopic Identification Tests 〈197〉, Infrared Spectroscopy: 197K or 197A

B. Identification Tests—General 〈191〉, Chemical Identification Tests, Sulfate

Sample solution: 50 mg/mL

Acceptance criteria: Meets the requirements

C. The retention time of the major peak of the Sample solution corresponds to that of the System suitability solution, as obtained in the Assay.

3 ASSAY

Procedure

Buffer: 1.8 g/L of monobasic potassium phosphate and 2.5 g/L of sodium 1-pentanesulfonate, adjusted with phosphoric acid to a pH of 2.5

Diluent: Acetonitrile and Buffer (20:80)

Solution A: Acetonitrile and Buffer (5:95)

Solution B: Acetonitrile and Buffer (80:20)

Mobile phase: See Table 1.

[Note—The gradient was established on an HPLC system with a dwell volume of approximately 0.8 mL.]

System suitability solution: 1 µg/mL of USP Hyoscyamine Related Compound A RS and 0.5 mg/mL of USP Atropine Sulfate RS in Diluent

Sensitivity solution: 0.25 µg/mL of USP Atropine Sulfate RS in Diluent

Standard solution: 0.5 mg/mL of USP Atropine Sulfate RS in Diluent

Sample solution: 0.5 mg/mL of Atropine Sulfate in Diluent

Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 210 nm

Column: 4.6-mm × 15-cm; 3-µm packing L1

Column temperature: 50°

Flow rate: 2 mL/min

Injection volume: 5 µL

System suitability

Samples: System suitability solution, Sensitivity solution, and Standard solution

[Note—See Table 2 for the relative retention times.]

Suitability requirements

Resolution: NLT 1.4 between hyoscyamine related compound A and atropine, System suitability solution

Tailing factor: 0.8–1.8 for atropine, System suitability solution

Relative standard deviation: NMT 0.73%, Standard solution

Signal-to-noise ratio: NLT 10 for atropine, Sensitivity solution

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of atropine sulfate (C₁₇H₂₃NO₃)₂·H₂SO₄·H₂O 

in the portion of Atropine Sulfate taken:

Result = (rᵤ/rₛ) × (Cₛ/Cᵤ) × 100

rᵤ = peak response of atropine from the Sample solution

rₛ = peak response of atropine from the Standard solution

Cₛ = concentration of USP Atropine Sulfate RS in the Standard solution (mg/mL)

Cᵤ = concentration of Atropine Sulfate in the Sample solution (mg/mL)

Acceptance criteria: 98.0%–102.0% on the anhydrous basis

4 IMPURITIES

Residue on Ignition 〈281〉: NMT 0.2%

Organic Impurities

Buffer, Diluent, Solution A, Solution B, Mobile phase, System suitability solution, Sensitivity solution, Standard solution, Sample solution, Chromatographic system, and System suitability: Proceed as directed in the Assay.

Analysis

Sample: Sample solution

Calculate the percentage of each impurity in the portion of Atropine Sulfate taken:

Result = (rᵢ/rₜ) × (1/F) × 100

rᵢ = peak response of each impurity from the Sample solution

rₜ = sum of all the peak responses from the Sample solution

F = relative response factor for each impurity (see Table 2)

Acceptance criteria: See Table 2. The reporting threshold is 0.05%.

a 3-Hydroxy-2-phenylpropanoic acid; also known as (2RS)-3-Hydroxy-2-phenylpropanoic acid.

b (1S,3R,5S)-6-Hydroxy-8-methyl-8-azabicyclo[3.2.1]oct-3-yl (S)-3-hydroxy-2-phenylpropanoate; also known as (1S,3R,5S,6RS)-6-Hydroxy-8-methyl-8-azabicyclo[3.2.1]oct-3-yl (2S)-3-hydroxy-2-phenylpropanoate.

c (S)-(1R,2R,4S,5S,7s)-9-Methyl-3-oxa-9-azatricyclo[3.3.1.02,4]nonan-7-yl 3-hydroxy-2-phenylpropanoate; also known as (S)-(1R,2R,4S,5S,7s)-9-Methyl-3-oxa-9-azatricyclo[3.3.1.02,4]non-7-yl (2S)-3-hydroxy-2-phenylpropanoate.

d (1R,3S,5R)-6-Hydroxy-8-methyl-8-azabicyclo[3.2.1]octan-3-yl (S)-3-hydroxy-2-phenylpropanoate; also known as (1R,3S,5R,6RS)-6-Hydroxy-8-methyl-8-azabicyclo[3.2.1]oct-3-yl (2S)-3-hydroxy-2-phenylpropanoate.

e (1R,3r,5S)-8-Methyl-8-azabicyclo[3.2.1]octan-3-yl 2-hydroxy-3-phenylpropanoate; also known as (1R,3r,5S)-8-Methyl-8-azabicyclo[3.2.1]oct-3-yl (2RS)-2-hydroxy-3-phenylpropanoate.

f (1R,3r,5S)-8-Methyl-8-azabicyclo[3.2.1]octan-3-yl 2-phenylacrylate; also known as (1R,3r,5S)-8-Methyl-8-azabicyclo[3.2.1]oct-3-yl 2-phenylpropenoate.

5 SPECIFIC TESTS

Optical Rotation 〈781S〉, Procedures, Specific Rotation

Sample solution: 0.1 g/mL of Atropine Sulfate in water

Temperature: 20°

Path length: 1.0 or 2.0 dm

Acceptance criteria: Between −0.50° and +0.05°

Water Determination 〈921〉, Method I : NMT 4.0%

6 ADDITIONAL REQUIREMENTS

Packaging and Storage: Preserve in tight, light-resistant containers.

USP Reference Standards 〈11〉

USP Atropine Sulfate RS

USP Hyoscyamine Related Compound A RS

Norhyoscyamine sulfate; (1R,3r,5S)-8-Azabicyclo[3.2.1]octan-3-yl (S)-3-hydroxy-2-phenylpropanoate sulfate (2:1).

(C₁₆H₂₁NO₃)₂·H₂SO₄ 648.77