Zaleplon Capsules
DEFINITION
Zaleplon Capsules contain NLT 90.0% and NMT 110.0% of zaleplon (C17H15N5O), calculated on the anhydrous basis.
IDENTIFICATION
• A. Ultraviolet Absorption 
197U
197U
Diluent:
Acetonitrile and water (1:4)
Standard solution:
0.1 mg/mL of USP Zaleplon RS in Diluent
Sample solution:
0.1 mg/mL of zaleplon in Diluent from the contents of NLT 5 Capsules
• B.
The retention time of the major peak of the Sample solution corresponds to that of the Standard solution, as obtained in the Assay.
ASSAY
• Procedure
Solution A:
0.3 g/L of ammonium formate in water
Solution B:
Acetonitrile
Diluent:
Acetonitrile and water (1:4)
Mobile phase:
See the gradient table below.
| Time (min) |
Solution A (%) |
Solution B (%) |
|---|---|---|
| 0 | 95 | 5 |
| 30 | 50 | 50 |
| 31 | 95 | 5 |
Standard solution:
0.1 mg/mL of USP Zaleplon RS in Diluent
Sample solution:
0.1 mg/mL of zaleplon in Diluent from NLT 5 Capsules. Pass through a filter of 0.45-µm pore size. [Note—Use the entire Capsule with its contents. Shake for 10 min. ]
Chromatographic system
Mode:
LC
Detector:
UV 240 nm
Column:
4.6-mm × 25-cm; 5-µm packing L1
Column temperature:
30
Flow rate:
1.4 mL/min
Injection size:
15 µL
System suitability
Sample:
Standard solution
Suitability requirements
Tailing factor:
NMT 1.5
Relative standard deviation:
NMT 2.0%
Analysis
Samples:
Standard solution and Sample solution
Calculate the percentage of zaleplon (C17H15N5O) in the portion of Capsules 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 Zaleplon RS in the Standard solution (mg/mL) |
| CU | = | = nominal concentration of zaleplon in the Sample solution (mg/mL) |
Acceptance criteria:
90.0%–110.0% on the anhydrous basis
PERFORMANCE TESTS
• Dissolution
Test 1
Medium:
Water; 900 mL
Apparatus 2:
75 rpm, with sinkers if necessary
Time:
20 min
Determine the percentage of zaleplon dissolved using one of the following procedures.
Spectrophotometric procedure
Standard stock solution:
11 mg of USP Zaleplon RS in a 250-mL volumetric flask, add 25.0 mL of methanol to dissolve. Dilute with Medium to volume. [Note—This solution is stable for 7 days. ]
Standard solution:
Dilute the Standard stock solution with Medium to obtain a final concentration of L/1000 mg/mL, where L is the Capsule label claim in mg. [Note—This solution is stable for 7 days. ]
Sample solution:
Pass a portion of the solution under test through a suitable filter of 0.45-µm pore size.
Instrumental conditions
Analytical wavelength:
333 nm
Path length:
1 cm
Blank:
Medium
Analysis
Samples:
Standard solution and Sample solution
Calculate the percentage of zaleplon (C17H15N5O) dissolved:
Result = (AU/AS) × (CS/L) × V × 100
| AU | = | = absorbance of the Sample solution |
| AS | = | = absorbance of the Standard solution |
| CS | = | = concentration of the Standard solution (mg/mL) |
| L | = | = label claim (mg/Capsule) |
| V | = | = volume of Medium, 900 mL |
Chromatographic procedure
Buffer:
0.77 g/L of ammonium acetate in water
Mobile phase:
Buffer and methanol (67:33)
Standard stock solution:
0.22 mg/mL of USP Zaleplon RS prepared as follows. Dissolve first in methanol using 5% of final volume and dilute with Medium to volume.
Standard solution:
Dilute the Standard stock solution with Medium to obtain a final concentration of (L/900) mg/mL, where L is the Capsule label claim in mg.
Sample solution:
Pass a portion of the solution under test through a suitable filter of 0.45-µm pore size.
Chromatographic system
Mode:
LC
Detector:
UV 230 nm
Column:
4.6-mm × 5-cm; 3-µm packing L1
Column temperature:
35
Flow rate:
2.0 mL/min
Injection size:
50 µL
System suitability
Sample:
Standard solution
Suitability requirements
Tailing factor:
NMT 1.5
Column efficiency:
NLT 2000 theoretical plates
Relative standard deviation:
NMT 2.0%
Analysis
Samples:
Standard solution and Sample solution
Calculate the percentage of zaleplon (C17H15N5O) 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 USP Zaleplon RS in the Standard solution (mg/mL) |
| L | = | = label claim (mg/Capsule) |
| V | = | = volume of Medium, 900 mL |
Tolerances:
NLT 85% (Q) of the labeled amount of zaleplon (C17H15N5O) is dissolved.
Test 2:
If the product complies with this test, the labeling indicates that the product meets USP Dissolution Test 2.
Medium:
Water; 900 mL
Apparatus 2:
75 rpm, with sinkers
Time:
20 min
Buffer:
1.36 g/L of monobasic potassium phosphate in water. Adjust with phosphoric acid to a pH of 3.0.
Mobile phase:
Buffer and acetonitrile (7:3)
Standard stock solution:
1.1 mg/mL of USP Zaleplon RS in Mobile phase
Standard solution:
Dilute the Standard stock solution with Medium to obtain a final concentration of (L/900) mg/mL, where L is the Capsule label claim in mg.
Sample solution:
Pass a portion of the solution under test through a suitable filter of 0.45-µm pore size.
Chromatographic system
Mode:
LC
Detector:
UV 225 nm
Column:
4.6-mm × 15-cm; 5-µm packing L1
Column temperature:
28
Flow rate:
1.5 mL/min
Injection size:
20 µL
System suitability
Sample:
Standard solution
Suitability requirements
Tailing factor:
NMT 2.0
Column efficiency:
NLT 2000 theoretical plates
Relative standard deviation:
NMT 2.0%
Analysis
Samples:
Standard solution and Sample solution
Calculate the percentage of zaleplon (C17H15N5O) 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 USP Zaleplon RS in the Standard solution (mg/mL) |
| L | = | = label claim (mg/Capsule) |
| V | = | = volume of Medium, 900 mL |
Tolerances:
NLT 80% (Q) of the labeled amount of zaleplon (C17H15N5O) is dissolved.
• Uniformity of Dosage Units 905:
Meet the requirements
905:
Meet the requirements
IMPURITIES
Organic Impurities
• Procedure
Diluent, Mobile phase, Sample solution, and Chromatographic system:
Proceed as directed in the Assay.
Standard stock solution:
0.5 mg/mL of USP Zaleplon RS in Diluent
System suitability solution:
0.5 µg/mL of USP Zaleplon Related Compound B RS in the Standard stock solution
Sensitivity solution:
0.05 µg/mL of USP Zaleplon RS in Diluent, from the Standard stock solution
Standard solution:
0.1 mg/mL of USP Zaleplon RS in Diluent, from the Standard stock solution
System suitability
Samples:
System suitability solution and Sensitivity solution
Suitability requirements
Signal-to-noise ratio:
NLT 10 for the zaleplon peak, Sensitivity solution
Resolution:
NLT 1.5 between zaleplon and zaleplon related compound B, System suitability solution
Tailing factor:
NMT 1.5 for the zaleplon peak, System suitability solution
Relative standard deviation:
NMT 2.0% for the zaleplon peak, System suitability solution
Analysis
Samples:
Standard solution and Sample solution
Calculate the percentage of any individual impurity in the portion of Capsules taken:
Result = (rU/rS) × (CS/CU) × 100
| rU | = | = peak response of an individual impurity from the Sample solution |
| rS | = | = peak response of USP Zaleplon RS from the Standard solution |
| CS | = | = concentration of USP Zaleplon RS in the Standard solution (mg/mL) |
| CU | = | = nominal concentration of zaleplon in the Sample solution (mg/mL) |
Acceptance criteria
Individual impurities:
See Impurity Table 1.
Total impurities:
NMT 1.0%
Impurity Table 1
| Name | Relative Retention Time |
Acceptance Criteria, NMT (%) |
|---|---|---|
| Cyanopyrazolaminea,* | 0.16 | — |
| Zaleplon related compound Ab,* | 0.76 | — |
| Zaleplon | 1.0 | — |
| Zaleplon related compound Bc,* | 1.05 | — |
| Any individual unspecified impurity | — | 0.2 |
|
a
3-Aminopyrazole-4-carbonitrile.
b
(E)-N-{3-[3-(Dimethylamino)acryloyl]phenyl}-N-ethylacetamide.
c
N-[3-(3-Cyanopyrazolo[1,5-
 ]pyrimidin-5-yl)phenyl]-N-ethylacetamide.
*
Included for peak identification purposes only.
|
||
ADDITIONAL REQUIREMENTS
• Packaging and Storage:
Preserve in light-resistant containers. Store at controlled room temperature.
• Labeling:
When more than one Dissolution test is given, the labeling states the Dissolution test used only if Test 1 is not used.
• USP Reference Standards 11
11
USP Zaleplon RS
USP Zaleplon Related Compound B RS
N-[3-(3-Cyanopyrazolo[1,5-]pyrimidin-5-yl)phenyl]-N-ethylacetamide.
C17H15N5O 305.33
N-[3-(3-Cyanopyrazolo[1,5-
]pyrimidin-5-yl)phenyl]-N-ethylacetamide.
C17H15N5O 305.33
Auxiliary Information—
Please check for your question in the FAQs before contacting USP.
| Topic/Question | Contact | Expert Committee |
|---|---|---|
| Monograph | Hariram Ramanathan, M.S.
Associate Scientific Liaison 1-301-816-8313 |
(SM42010) Monographs - Small Molecules 4 |
| Reference Standards | RS Technical Services 1-301-816-8129 rstech@usp.org |
USP35–NF30 Page 5059
Pharmacopeial Forum: Volume No. 36(4) Page 939