Glycopyrrolate Tablets

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

Glycopyrrolate Tablets contain NLT 93.0% and NMT 107.0% of the labeled amount of glycopyrrolate (C₁₉H₂₈BrNO₃). 

2 IDENTIFICATION

A. The retention time of the major peak of the Sample solution corresponds to that of the Standard solution, as obtained in the Assay. Add the following:

B. The UV spectrum of the major peak of the Sample solution corresponds to that of the Standard solution, as obtained in the Assay. _{(USP 1- Aug-2019)}

3 ASSAY

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Procedure

Buffer solution: Prepare a solution of 1.0 g of sodium sulfate anhydrous and 200 mg of sodium 1-hexanesulfonate monohydrate in 650 mL of water. To this solution add 3.0 mL of 1 N sulfuric acid, and mix.

Mobile phase: Acetonitrile, methanol, and Buffer solution (20:15:65)

Standard solution: 0.1 mg/mL of USP Glycopyrrolate RS in Mobile phase

Sample solution: Nominally _{(USP 1-Aug-2019)} 0.1 mg/mL of glycopyrrolate in Mobile phase. Prepare by transferring 10 Tablets to a suitable volumetric flask. Add Mobile phase to 50% of the volume of the flask, and sonicate for 10 min or until the Tablets disintegrate completely. Add Mobile phase to 75% of the volume of the flask, shake mechanically for 30 min, and dilute with Mobile phase to volume. Centrifuge aportion of the solution, and pass the supernatant through a suitable filter, discarding the first few milliliters of the filtrate.

3.1 Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 222 nm. For Identification B, use a diode array detector in the range of 210–400 nm. _{(USP 1-Aug-2019)}

Column: 4.6-mm × 15-cm; 5-µm packing L1

Column temperature: 40°

Flow rate: 1.2 mL/min

Injection volume: 50 µL

3.2 System suitability

Sample: Standard solution

Suitability requirements

Tailing factor: NMT 2.0

Relative standard deviation: NMT 1.0%

3.3 Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amount of glycopyrrolate (C₁₉H₂₈BrNO₃) in the portion of Tablets taken: 

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

r_U = peak response of glycopyrrolate from the Sample solution

r_S = peak response of glycopyrrolate from the Standard solution

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

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

Acceptance criteria: 93.0%–107.0%

4 PERFORMANCE TESTS

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Dissolution 〈711〉

Medium: Water; 500 mL

Apparatus 1: 100 rpm

Time: 45 min

Buffer solution: 1.0 g of sodium sulfate anhydrous and 200 mg of sodium 1-pentanesulfonate in 620 mL of water

Mobile phase: Acetonitrile, methanol, Buffer solution, and 1 N sulfuric acid (200:180:620:3)

Standard stock solution: 0.2 mg/mL of USP Glycopyrrolate RS in Medium. A small volume of methanol, not exceeding 20% of the nal volume, can be used to solubilize glycopyrrolate.

Standard solution: (L/500) mg/mL of glycopyrrolate in Medium from the Standard stock solution, where L is the label claim in mg/Tablet. Prepare this solution fresh, and refrigerate immediately at 5°.

Sample solution: Pass a portion of the solution under test through a suitable filter, discarding the first few milliliters of the filtrate. Refrigerate the samples at 5°.

4.1 Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 210 nm

Column: 4.6-mm × 15-cm; 5-µm packing L1

Temperatures

Autosampler: 5°

Column: 40°

Flow rate: 1.2 mL/min

Injection volume: 80 µL

4.2 System suitability

Sample: Standard solution

Suitability requirements

Tailing factor: NMT 2.0

Relative standard deviation: NMT 2.0%

4.3 Analysis

Samples: Standard solution and Sample solution

Calculate the _{(USP 1-Aug-2019)} percentage of the labeled amount of glycopyrrolate dissolved:

Result = (r_U /r_S) × (C_S /L) × V × 100

r_U = peak response from the Sample solution

r_S = peak response from the Standard solution

C_S = concentration of USP Glycopyrrolate RS _{(USP 1-Aug-2019)} in the Standard solution (mg/mL)

L = label claim (mg/Tablet)

V = volume of Medium, 500 mL

Tolerances: NLT 75% (Q) of the labeled amount of glycopyrrolate (C₁₉H₂₈BrNO₃) is dissolved.

Uniformity of Dosage Units 〈905〉: Meet the requirements

5 IMPURITIES

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Organic Impurities

Buffer solution: Prepare a solution of 1.0 g of sodium sulfate anhydrous and 200 mg of sodium 1-hexanesulfonate monohydrate in 650 mL of water. To this solution add 3.0 mL of 1 N sulfuric acid, and mix.

Diluent: Prepare a solution of 1.0 g of sodium sulfate anhydrous, 6.8 g of monobasic potassium phosphate, and 200 mg of sodium 1- hexanesulfonate monohydrate in 650 mL of water. To this solution add 3.0 mL of 1 N sulfuric acid, 150 mL of methanol, and 200 mL of acetonitrile, and mix. Adjust with phosphoric acid to a pH of 2.8.

Solution A: Acetonitrile, methanol, and Buffer solution (20:15:65)

Solution B: Acetonitrile, methanol, and Buffer solution (50:15:35)

Mobile phase: See Table 1.

Table 1

Standard solution: 0.0015 mg/mL each of USP Glycopyrrolate RS, USP Glycopyrrolate Related Compound B RS, and USP Glycopyrrolate Related Compound C RS in Diluent. Sonicate, if necessary, to facilitate dissolution.

Sample solution: Nominally _{(USP 1-Aug-2019)} 0.5 mg/mL of glycopyrrolate in Diluent. Prepare by transferring the equivalent of 25 mg of glycopyrrolate from a portion of NLT 20 powdered Tablets to a 50-mL volumetric ask. Add 30 mL of Diluent, sonicate for 10 min, shake mechanically for 30 min, and dilute with Diluent to volume. Centrifuge a portion of the solution, and pass the supernatant through a suitable filter, discarding the first few milliliters of the filtrate.

5.1 Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 222 nm

Column: 4.6-mm × 15-cm; 5-µm packing L1

Column temperature: 40°

Flow rate: 1 mL/min

Injection volume: 50 µL

5.2 System suitability

Sample: Standard solution

Suitability requirements

Resolution: NLT 2.0 between glycopyrrolate and glycopyrrolate related compound B

Tailing factor: NMT 2.0 for the glycopyrrolate peak

Relative standard deviation: NMT 6.0% for the glycopyrrolate and glycopyrrolate related compound C peaks

5.3 Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of glycopyrrolate related compound C in the portion of Tablets taken:

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

r_U = peak response of glycopyrrolate related compound C from the Sample solution

r_S = peak response of glycopyrrolate related compound C from the Standard solution

C_S = concentration of USP Glycopyrrolate Related Compound C RS in the Standard solution (mg/mL)

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

Calculate the percentage of any other individual impurity in the portion of Tablets taken:

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

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

r_S = peak response of glycopyrrolate from the Standard solution

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

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

Acceptance criteria: See Table 2.

Table 2

^a Glycopyrrolate related compound A.

^b Disregard the peaks due to 5-nitroisophthalic acid and glycopyrrolate base, because these are process impurities and are controlled in the drug substance monograph.

^c Glycopyrrolate related compound B.

^d Glycopyrrolate related compound C.

6 ADDITIONAL REQUIREMENTS

Packaging and Storage: Preserve in tight containers. Store at controlled room temperature.

Change to read:

USP Reference Standards 〈11〉

USP Glycopyrrolate RS

USP Glycopyrrolate Related Compound B RS

[Note—May be available as a free base or a hydrochloride salt.] (USP 1-Aug-2019)

1-Methylpyrrolidin-3-yl-2-cyclopentyl-2-hydroxy-2-phenylacetate.

C₁₈H₂₅NO₃             303.40

1-Methylpyrrolidin-3-yl 2-cyclopentyl-2-hydroxy-2-phenylacetate hydrochloride.

C₁₈H₂₅NO₃ · HCl          339.86  (USP 1-Aug-2019)

USP Glycopyrrolate Related Compound C RS

2-Cyclopentyl-2-hydroxy-2-phenylacetic acid.

C₁₃H₁₆O₃               220.26