Hyoscyamine 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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1 DEFINITION

Hyoscyamine Sulfate contains NLT 98.0% and NMT 102.0% of hyoscyamine sulfate [(C₃₄H₄₈NO₁₀) · H₂SO₄], calculated on the anhydrous basis.

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

2 IDENTIFICATION

Change to read:

A. ▲Spectroscopic Identification Tests 〈197〉, Infrared Spectroscopy, 197A or 197K:▲ (CN 1-May-2020)

Meets the requirements.

B. The retention time of the major peak of the Sample solution corresponds to that of the Standard solution, as obtained in the Assay.

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

Sample solution: 50 mg/mL

Acceptance criteria: Meets the requirements

3 ASSAY

Procedure

Buffer: 7.0 g/L of monobasic potassium phosphate, adjusted with 0.05 M phosphoric acid to a pH of 3.3

Solution A: Dissolve 3.5 g of sodium dodecyl sulfate in 606 mL of Buffer, add 320 mL of acetonitrile, and mix.

Solution B: Acetonitrile

Mobile phase: See Table 1. Return to original conditions and re-equilibrate the system.

Table 1

Standard solution: 0.24 mg/mL of USP Hyoscyamine Sulfate RS in Solution A

Sample solution: 0.24 mg/mL of Hyoscyamine Sulfate in Solution A

Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 210 nm

Column: 4.6-mm × 10-cm; 3-µm packing L1

Flow rate: 1.0 mL/min

Injection volume: 10 µL

System suitability

Sample: Standard solution

Suitability requirements

Tailing factor: NMT 2.0

Relative standard deviation: NMT 0.73%

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of hyoscyamine sulfate [(C₃₄H₄₈NO₁₀) · H₂SO₄] in the portion of Hyoscyamine Sulfate taken:

Result = (rᵤ / rₛ) × (Cₛ / Cᵤ) × 100

rᵤ = peak response from the Sample solution

rₛ = peak response from the Standard solution

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

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

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

4 IMPURITIES

Residue on Ignition 〈281〉: NMT 0.1%

Organic Impurities

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

Standard stock solution: 1.2 mg/mL of USP Hyoscyamine Sulfate RS in Solution A

Standard solution: 0.24 µg/mL of USP Hyoscyamine Sulfate RS from the Standard stock solution in Solution A

System suitability stock solution: 2.4 µg/mL of USP Hyoscyamine Related Compound A RS in Solution A

System suitability solution: Transfer 5.0 mL of System suitability stock solution to a 50-mL volumetric flask, add 10 mL of the Standard stock solution, and dilute with Solution A to volume.

System suitability

Samples: Standard solution and System suitability solution

Suitability requirements

Resolution: NLT 2.0 between hyoscyamine related compound A and hyoscyamine, System suitability solution

Relative standard deviation: NMT 10.0%, Standard solution

Analysis

Samples: Sample solution and Standard solution

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

Result = (rᵢ / rₛ) × (Cₛ / Cᵤ) × (1/F) × 100

rᵢ = peak response of each impurity from the Sample solution

rₛ = peak response of hyoscyamine from the Standard solution

Cₛ = concentration of USP Hyoscyamine Sulfate RS in the Standard solution (µg/mL)

Cᵤ = concentration of Hyoscyamine Sulfate in the Sample solution (µg/mL)

F = relative response factor (see Table 2)

Acceptance criteria: See Table 2.

Table 2

5 SPECIFIC TESTS

Optical Rotation 〈781S〉, Procedures, Specific Rotation

Sample solution: 50 mg/mL in water

Acceptance criteria: −24° to −29°, measured at 20°

Water Determination 〈921〉, Method I, Method Ia: 2.0%–5.5%

6 ADDITIONAL REQUIREMENTS

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

USP Reference Standards 〈11〉

USP Hyoscyamine Sulfate RS

USP Hyoscyamine Related Compound A RS

Norhyoscyamine sulfate;

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

C₃₂H₄₄N₂O₁₀S  648.77