Glycopyrrolate Tablets
The retention time of the major peak of the Sample solution corresponds to that of the Standard solution, as obtained in the Assay.USP35
Buffer:
Prepare a solution of 1.0 g of anhydrous sodium sulfate 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.
711
USP35
Buffer:
1.0 g of anhydrous sodium sulfate and 200 mg of sodium 1-pentanesulfonate in 620 mL of water
• Organic Impurities
USP35
Store at controlled room temperature.USP35
11
USP Glycopyrrolate Related Compound B RS
1-Methylpyrrolidin-3-yl-2-cyclopentyl-2-hydroxy-2-phenylacetate.
C18H25NO3 303.40
USP35
DEFINITION
Glycopyrrolate Tablets contain NLT 93.0% and NMT 107.0% of the labeled amount of glycopyrrolate (C19H28BrNO3).
IDENTIFICATION
Change to read:
• A.
The retention time of the major peak of the Sample solution corresponds to that of the Standard solution, as obtained in the Assay.USP35
ASSAY
Change to read:
• Procedure
Buffer:
Prepare a solution of 1.0 g of anhydrous sodium sulfate 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 (20:15:65)
Standard solution:
0.1 mg/mL of USP Glycopyrrolate RS in Mobile phase
Sample solution:
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 a portion of the solution, and pass the supernatant through a suitable filter, discarding the first few mL of the filtrate.
Chromatographic system
Mode:
LC
Detector:
UV 222 nm
Column:
4.6-mm × 15-cm; 5-µm packing L1
Column temperature:
40
Flow rate:
1.2 mL/min
Injection size:
50 µL
System suitability
Sample:
Standard solution
Suitability requirements
Tailing factor:
NMT 2.0
Relative standard deviation:
NMT 1.0%
Analysis
Samples:
Standard solution and Sample solution
Calculate the percentage of the labeled amount of glycopyrrolate (C19H28BrNO3) in the portion of Tablets taken:
Result = (rU/rS) × (CS/CU) × 100
| rU | = | = peak response of glycopyrrolate from the Sample solution |
| rS | = | = peak response of glycopyrrolate from the Standard solution |
| CS | = | = concentration of USP Glycopyrrolate RS in the Standard solution (mg/mL) |
| CU | = | = nominal concentration of glycopyrrolate in the Sample solution (mg/mL) |
Acceptance criteria:
93.0%–107.0%USP35
USP35
PERFORMANCE TESTS
Change to read:
• Dissolution 711
USP35
Medium:
Water; 500 mL
Apparatus 1:
100 rpm
Time:
45 min
Buffer:
1.0 g of anhydrous sodium sulfate and 200 mg of sodium 1-pentanesulfonate in 620 mL of water
Mobile phase:
Acetonitrile, methanol, Buffer, 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 final 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 mL of the filtrate. Refrigerate the samples at 5.
.
Chromatographic system
Mode:
LC
Detector:
UV 210 nm
Column:
4.6-mm × 15-cm; 5-µm packing L1
Temperature
Column:
40
Sampler:
5
Flow rate:
1.2 mL/min
Injection size:
80 µL
System suitability
Sample:
Standard solution
Suitability requirements
USP35
Tailing factor:
NMT 2.0
Relative standard deviation:
NMT 2.0%
Calculate the average percentage of the labeled amount of glycopyrrolate dissolved:
Result = (rU/rS) × (CS/L) × V × 100
| rU | = | = peak response from the Sample solution |
| rS | = | = peak response from the Standard solution |
| CS | = | = concentration of glycopyrrolate in the Standard solution (mg/mL) |
| L | = | = label claim (mg/Tablet) |
| V | = | = volume of Medium, 500 mL |
USP35
Tolerances:
NLT 75% (Q) of the labeled amount of glycopyrrolate (C19H28BrNO3) is dissolved.
• Uniformity of Dosage Units 905:
Meet the requirements
905:
Meet the requirements
IMPURITIES
Add the following:
• Organic Impurities
Buffer:
Prepare a solution of 1.0 g of anhydrous sodium sulfate 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 anhydrous sodium sulfate, 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 (20:15:65)
Solution B:
Acetonitrile, methanol, and Buffer (50:15:35)
Mobile phase:
See Table 1.
Table 1
| Time (min) |
Solution A (%) |
Solution B (%) |
|---|---|---|
| 0 | 100 | 0 |
| 10 | 100 | 0 |
| 25 | 10 | 90 |
| 35 | 10 | 90 |
| 37 | 100 | 0 |
| 45 | 100 | 0 |
Standard solution:
1.5 µg/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:
500 µg/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 flask. 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 mL of the filtrate.
Chromatographic system
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 size:
50 µL
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
Analysis
Samples:
Standard solution and Sample solution
Calculate the percentage of glycopyrrolate related compound C in the portion of Tablets taken:
Result = (rU/rS) × (CS/CU) × 100
| rU | = | = peak response of glycopyrrolate related compound C from the Sample solution |
| rS | = | = peak response of glycopyrrolate related compound C from the Standard solution |
| CS | = | = concentration of USP Glycopyrrolate Related Compound C RS in the Standard solution (mg/mL) |
| CU | = | = 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 = (rU/rS) × (CS/CU) × 100
| rU | = | = peak response of each impurity from the Sample solution |
| rS | = | = peak response of glycopyrrolate from the Standard solution |
| CS | = | = concentration of USP Glycopyrrolate RS in the Standard solution (mg/mL) |
| CU | = | = nominal concentration of glycopyrrolate in the Sample solution (mg/mL) |
Acceptance criteria:
See Table 2.
Table 2
| Name | Relative Retention Time |
Acceptance Criteria, NMT (%) |
|---|---|---|
| 5-Nitroisophthalic acida | 0.45 | —d |
| Glycopyrrolate | 1.00 | — |
| Glycopyrrolate baseb | 1.14 | —d |
| Cyclopentylmandelic acidc | 2.68 | 0.5 |
| Any other individual impurity | — | 0.2 |
| Total impurities | — | 1.2 |
|
a
Glycopyrrolate related compound A.
b
Glycopyrrolate related compound B.
c
Glycopyrrolate related compound C.
d
Disregard the peaks due to 5-nitroisophthalic acid and glycopyrrolate base, because these are process impurities and are controlled in the drug substance monograph.
|
||
USP35ADDITIONAL REQUIREMENTS
Change to read:
• Packaging and Storage:
Preserve in tight containers. Store at controlled room temperature.USP35
Change to read:
• USP Reference Standards 11
USP Glycopyrrolate RS 
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USP Glycopyrrolate Related Compound B RS
1-Methylpyrrolidin-3-yl-2-cyclopentyl-2-hydroxy-2-phenylacetate.
C18H25NO3 303.40
USP Glycopyrrolate Related Compound C RS
2-Cyclopentyl-2-hydroxy-2-phenylacetic acid.
C13H16O3 220.26
2-Cyclopentyl-2-hydroxy-2-phenylacetic acid.
C13H16O3 220.26
USP35
Auxiliary Information—
Please check for your question in the FAQs before contacting USP.
| Topic/Question | Contact | Expert Committee |
|---|---|---|
| Monograph | Elena Gonikberg, Ph.D.
Principal Scientific Liaison 1-301-816-8251 |
(SM32010) Monographs - Small Molecules 3 |
| 711 |
Margareth R.C. Marques, Ph.D.
Senior Scientific Liaison 1-301-816-8106 |
(GCDF2010) General Chapters - Dosage Forms |
| Reference Standards | RS Technical Services 1-301-816-8129 rstech@usp.org |
USP35–NF30 Page 3359
Pharmacopeial Forum: Volume No. 37(1)