Bisacodyl

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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C₂₂H₁₉NO₄  361.39

Phenol, 4,4'-(2-pyridinylmethylene)bis-, diacetate (ester);

4,4'-(2-Pyridylmethylene)diphenol diacetate (ester);

4,4'-(Pyridin-2-ylmethylene) diphenyl diacetate CAS RN^®: 603-50-9.

1 DEFINITION

Bisacodyl contains NLT 98.0% and NMT 102.0% of bisacodyl (C₂₂H₁₉NO₄), calculated on the dried basis. [CAUTION-Avoid inhalation and contact with the eyes, skin, and mucous membranes.]

2 IDENTIFICATION

Change to read:

A. ASPECTROSCOPIC 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.

3 ASSAY

3.1 PROCEDURE

Buffer: 1.58 g/L of ammonium formate in water; adjusted with formic acid to a pH of 5.0

Mobile phase: Acetonitrile and Buffer (45:55)

Diluent: Acetonitrile, acetic acid, and water (30:4:66)

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

Sample solution: 0.5 mg/mL of Bisacodyl in Diluent

Chromatographic system

(See Chromatography (621), System Suitability.)

Mode: LC

Detector: UV 265 nm

Column: 4.6-mm × 25-cm; 5-µm packing L1

Flow rate: 1.5 mL/min

Injection volume: 10 µL

Run time: NLT 2 times the retention time of bisacodyl

System suitability

Sample: Standard solution

Suitability requirements

Tailing factor: NMT 1.5

Relative standard deviation: NMT 0.73%

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of bisacodyl (C₂₂H₁₉NO₄) in the portion of Bisacodyl taken:

Result = (r_U/r_S) × (C_S/C_U) × 100

r_U = peak response of bisacodyl from the Sample solution

r_S = peak response of bisacodyl from the Standard solution

C_S = concentration of USP Bisacodyl RS in the Standard solution (mg/mL)

C_U = concentration of Bisacodyl in the Sample solution (mg/mL)

Acceptance criteria: 98.0%-102.0% on the dried basis

4 IMPURITIES

4.1 RESIDUE ON IGNITION (281)

NMT 0.1%

4.2 ORGANIC IMPURITIES

Buffer: 1.58 g/L of ammonium formate in water; adjusted with formic acid to a pH of 5.0

Mobile phase: Acetonitrile and Buffer (45:55)

Diluent: Acetonitrile and water (35:5)

System suitability solution: 0.8 mg/mL of USP Bisacodyl RS; 2 µg/mL each of USP Bisacodyl Related Compound A RS, USP Bisacodyl Related Compound C RS, and USP Bisacodyl Related Compound E RS; and 4 µg/mL of USP Bisacodyl Related Compound B RS in Diluent

Sensitivity solution: 0.0003 mg/mL of USP Bisacodyl RS in Diluent

Standard stock solution: 1.0 mg/mL of USP Bisacodyl RS in Diluent

Standard solution: 1.0 µg/mL of USP Bisacodyl RS in Diluent

Sample solution: 1.0 mg/mL of Bisacodyl in Diluent

Chromatographic system

(See Chromatography (621), System Suitability.)

Mode: LC

Detector: UV 265 nm

Column: 4.6-mm x 25-cm; 4- or 5-µm packing L1

Flow rate: 1.5 mL/min

Injection volume: 20 µL

Run time: NLT 3.5 times the retention time of bisacodyl

System suitability

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

[NOTE-See Table 1 for the relative retention times.]

Suitability requirements

Resolution: NLT 1.5 between the bisacodyl related compound E and bisacodyl peaks, System suitability solution

Tailing factor: NMT 2.0 for the bisacodyl peak, System suitability solution

Relative standard deviation: NMT 5.0% for the bisacodyl peak, Standard solution

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

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of each individual impurity in the portion of Bisacodyl taken:

Result = (r_U/r_S) × (C_S/C_U) × (1/F) × 100

r_U = peak response of each individual impurity from the Sample solution

r_S = peak response of bisacodyl from the Standard solution

C_S = concentration of the Standard solution (mg/mL)

C_U = concentration of the Sample solution (mg/mL)

F = relative response factor (see Table 1)

Acceptance criteria: See Table 1. The reporting threshold is 0.05%.

Table 1

5 SPECIFIC TESTS

LOSS ON DRYING (731)

Analysis: Dry at 105° for 2 h.

Acceptance criteria: NMT 0.5%

6 ADDITIONAL REQUIREMENTS

PACKAGING AND STORAGE: Preserve in well-closed containers, protected from light. Store at room temperature.

USP REFERENCE STANDARDS (11)

USP Bisacodyl RS

USP Bisacodyl Related Compound A RS

4,4'-(Pyridin-2-ylmethylene)diphenol.

C₁₈H₁₅NO₂  277.32

USP Bisacodyl Related Compound B. RS

2,4'-(Pyridin-2-ylmethylene)diphenol.

C₁₈H₁₅NO₂  277.32

USP Bisacodyl Related Compound C RS

4-[(4-Hydroxyphenyl) (pyridin-2-yl)methyl]phenyl acetate.

C₂₀H₁₇NO₃  319.35

USP Bisacodyl Related Compound E RS

2-[(4-Acetoxyphenyl) (pyridin-2-yl)methyl]phenyl acetate.

C₂₂H₁₉NO₄  361.39