Pindolol

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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C₁₄H₂₀N₂O₂ 248.33

2-Propanol, 1-(1H-indol-4-yloxy)-3-(1-methylethyl)amino-;

1-(Indol-4-yloxy)-3-(isopropylamino)-2-propanol CAS RN^®: 13523-86-9; UNII: BJ4HF6IU1D.

1 DEFINITION

Pindolol contains NLT 98.5% and NMT 101.0% of pindolol (C₁₄H₂₀N₂O₂), calculated on the dried basis.

2 IDENTIFICATION

A. SPECTROSCOPIC IDENTIFICATION TESTS (197), Infrared Spectroscopy: 197A or 197K

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

Change to read:

3.1 PROCEDURE

Mobile phase: Acetonitrile and 0.05 M sodium acetate, previously adjusted with glacial acetic acid to a pH of 5.0 (350:650)

System suitability solution: 0.005 mg/mL each of USP Pindolol RS and USP Indole RS in Mobile phase

Standard stock solution: 1 mg/mL of USP Pindolol RS in Mobile phase prepared as follows. To a suitable amount of USP Pindolol RS add Mobile phase to fill about 90% of the total volume, and sonicate for about 5 min to dissolve. Dilute with Mobile phase to volume. (ERR 1-May-2023)

Standard solution: 0.1 mg/mL of USP Pindolol RS from Standard stock solution in Mobile phase

Sample stock solution: 1 mg/mL of Pindolol in Mobile phase prepared as follows. To a suitable amount of Pindolol add Mobile phase to fill about 90% of the total volume, and sonicate for about 5 min to dissolve. Dilute with Mobile phase to volume.

Sample solution: 0.1 mg/mL of Pindolol from Sample stock solution in Mobile phase

3.2 Chromatographic system

(See Chromatography (621), System Suitability.)

Mode: LC

Detector: UV 219 nm

Column: 4.6-mm x 15-cm; 3-µm packing L10

Flow rate: 1 mL/min

Injection volume: 10 µL

Run time: NLT 2 times the retention time for pindolol

3.3 System suitability

Samples: System suitability solution and Standard solution

[NOTE-The relative retention times for indole and pindolol are 0.5 and 1.0, respectively.]

Suitability requirements

Resolution: NLT 7 between indole and pindolol, System suitability solution

Tailing factor: NMT 2.0, Standard solution

Relative standard deviation: NMT 0.73%, Standard solution

3.4 Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of pindolol (C₁₄H₂₀N₂O₂) in the portion of Pindolol taken:

Result = (r_U/r_S) x (C_S/C_U) x 100

r_U = peak response of pindolol from the Sample solution

r_S = peak response of pindolol from the Standard solution

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

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

Acceptance criteria: 98.5%-101.0% on the dried basis

4 IMPURITIES

4.1 RESIDUE ON IGNITION (281)

NMT 0.1%

4.2 ORGANIC IMPURITIES

Solution A: 0.05 M sodium acetate. Adjust with glacial acetic acid to a pH of 5.0.

Mobile phase: Acetonitrile and Solution A (50:50)

System suitability solution: 0.003 mg/mL of USP Pindolol RS and 0.005 mg/mL of USP Indole RS in Mobile phase. [NOTE-Sonication may be needed to aid in the dissolution.]

Standard solution: 0.003 mg/mL of USP Pindolol RS and 0.005 mg/mL of USP 4-Hydroxyindole RS in Mobile phase. [Note-Sonication may be needed to aid in the dissolution.]

Sensitivity solution: 0.5 µg/mL of USP Pindolol RS from Standard solution in Mobile phase

Sample solution: Use the Sample stock solution, prepared as directed in the Assay.

Chromatographic system

(See Chromatography (621), System Suitability.)

Mode: LC

Detector: UV 264 nm

Column: 4.6-mm x 15-cm; 3-µm packing L10

Flow rate: 1 mL/min

Injection volume: 10 µL

Run time: NLT 3 times the retention time of the pindolol peak

System suitability

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

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

Suitability requirements

Resolution: NLT 7 between indole and pindolol, System suitability solution

Relative standard deviation: NMT 2% for 4-hydroxyindole and pindolol, Standard solution

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

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the specified impurity, 4-hydroxyindole, in the portion of Pindolol taken:

Result = (r_U/r_S) x (C_S/C_U) x 100

r_U = peak response of 4-hydroxyindole from the Sample solution

r_S = peak response of 4-hydroxyindole from the Standard solution

C_S = concentration of USP 4-Hydroxyindole RS in the Standard solution (mg/mL)

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

Calculate the percentage of any individual unspecified impurity in the portion of Pindolol taken:

Result = (r_U/r_S) x (C_S/C_U) x 100

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

r_S = peak response of pindolol from the Standard solution

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

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

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

Table 1

^a For resolution measurement only. It is not to be reported or included in the total impurities.

5 SPECIFIC TESTS

LOSS ON DRYING (731)

Analysis: Dry at 105° for 4 h.

Acceptance criteria: NMT 0.5%

6 ADDITIONAL REQUIREMENTS

6.1 PACKAGING AND STORAGE

Preserve in well-closed containers, protected from light.

6.2 USP REFERENCE STANDARDS (11)

USP 4-Hydroxyindole RS

1H-Indol-4-ol.

C₈H₇NO 133.15

USP Indole RS

Indole.

C₈H₇N 117.15

USP Pindolol RS