Add the following:
Alprazolam Orally Disintegrating Tablets
DEFINITION
Alprazolam Orally Disintegrating Tablets contain NLT 90.0% and NMT 110.0% of the labeled amount of alprazolam (C17H13ClN4).
IDENTIFICATION
• 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
Buffer:
6.8 g/L of monobasic potassium phosphate in water. Adjust with phosphoric acid to a pH of 3.5.
Diluent:
Acetonitrile and water (3:2)
Mobile phase:
Acetonitrile, methanol, and Buffer (7:2:11)
Standard solution:
10 µg/mL of USP Alprazolam RS in Diluent
Sample solution:
10 µg/mL of alprazolam in Diluent. Prepare using 10 Tablets, and pass through a suitable filter. [Note—Sonicate with intermittent shaking to help dissolve, if necessary. ]
Chromatographic system
Mode:
LC
Detector:
UV 221 nm
Column:
4.6-mm × 15-cm; 5-µm packing L7
Column temperature:
30
Flow rate:
1.5 mL/min
Injection size:
30 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 alprazolam (C17H13ClN4) in the portion of Tablets 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 Alprazolam RS in the Standard solution (µg/mL) |
| CU | = | = nominal concentration of alprazolam in the Sample solution (µg/mL) |
Acceptance criteria:
90.0%–110.0%
PERFORMANCE TESTS
• Disintegration 
701
701
Time:
NMT 60 s
• Dissolution 711
711
Medium:
pH 6.0 phosphate buffer (80 g/L of monobasic potassium phosphate and 20 g/L of dibasic potassium phosphate in water. Adjust with phosphoric acid or diluted sodium hydroxide to a pH of 6.0 ± 0.1); 900 mL
Apparatus 2:
50 rpm
Time:
10 min
Mobile phase, Chromatographic system, and System suitability:
Proceed as directed in the Assay, except use an injection size of 100 µL.
Standard stock solution:
50 µg/mL of USP Aprazolam RS in methanol. [Note—Sonicate to help dissolve, if necessary. ]
Standard solution:
L/1000 µg/mL of USP Aprazolam RS in Medium from the Standard stock solution, where L is the Tablet label claim in µg
Sample solution:
Pass a portion of the solution under test through a nylon membrane filter of 0.45-µm pore size, discarding the first few mL.
Analysis
Samples:
Standard solution and Sample solution
Calculate the percentage of alprazolam (C17H13ClN4) dissolved:
Result = (rU/rS) × CS × (V/L) × 100
| rU | = | = peak response from the Sample solution |
| rS | = | = peak response from the Standard solution |
| CS | = | = concentration of USP Alprazolam RS in the Standard solution (mg/mL) |
| V | = | = volume of Medium, 900 mL |
| L | = | = label claim (mg/Tablet) |
Tolerances:
NLT 80% (Q) of the label claim of C17H13ClN4 is dissolved.
• Uniformity of Dosage Units 905:
Meet the requirements
905:
Meet the requirements
IMPURITIES
Organic Impurities
• Procedure
Buffer and Diluent:
Prepare as directed in the Assay.
Solution A:
Acetonitrile, methanol, and Buffer (5:4:11)
Solution B:
Acetonitrile, methanol, and Buffer (8:1:11)
Mobile phase:
See the gradient table below.
| Time (min) |
Solution A (%) |
Solution B (%) |
|---|---|---|
| 0 | 100 | 0 |
| 12 | 100 | 0 |
| 15 | 0 | 100 |
| 60 | 0 | 100 |
| 65 | 100 | 0 |
| 70 | 100 | 0 |
Standard solution:
0.6 µg/mL of USP Alprazolam RS in Diluent
Sample solution:
200 µg/mL of alprazolam in Diluent. Prepare using 10 Tablets, and pass through a suitable filter.
Chromatographic system
Mode:
LC
Detector:
UV 240 nm
Column:
4.6-mm × 15-cm; 5-µm packing L7
Column temperature:
30
Flow rate:
1.2 mL/min
Injection size:
25 µL
System suitability
Sample:
Standard solution
Suitability requirements
Theoretical plates:
NLT 2000
Tailing factor:
NMT 1.5
Relative standard deviation:
NMT 6.0%
Analysis
Samples:
Standard solution and Sample solution
Calculate the percentage of each impurity in the portion of Tablets taken:
Result = (rU/rS) × (CS/CU) × (1/F) × 100
| rU | = | = peak response of each impurity from the Sample solution |
| rS | = | = peak response of alprazolam from the Standard solution |
| CS | = | = concentration of USP Alprazolam RS in the Standard solution (µg/mL) |
| CU | = | = nominal concentration of alprazolam in the Sample solution (µg/mL) |
| F | = | = relative response factor (see Impurity Table 1) |
Acceptance criteria
Individual impurities:
See Impurity Table 1.
Total impurities:
NMT 2.0%. [Note—Disregard any peaks less than 0.05%. ]
Impurity Table 1
| Name | Relative Retention Time |
Relative Response Factor |
Acceptance Criteria, NMT (%) |
|---|---|---|---|
| Alprazolam related compound Aa,b | 0.8 | — | — |
| Alprazolam | 1.0 | — | — |
| 2-Amino-5-chlorobenzophenone | 2.9 | 1.9 | 0.5 |
| Any other unknown impurity | — | 1.0 | 0.5 |
|
a
2-(2-Acetylhydrazino)-7-chloro-5-phenyl-3H-1,4-benzodiazepine.
b
Disregard the peak due to alprazolam related compound A, because it is a process impurity in alprazolam.
|
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ADDITIONAL REQUIREMENTS
• Packaging and Storage:
Preserve in tight containers, and store at controlled room temperature.
• USP Reference Standards 11
11
USP Alprazolam RS 
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USP35
Auxiliary Information—
Please check for your question in the FAQs before contacting USP.
| Topic/Question | Contact | Expert Committee |
|---|---|---|
| Monograph | Ravi Ravichandran, Ph.D.
Principal Scientific Liaison 1-301-816-8330 |
(SM42010) Monographs - Small Molecules 4 |
| 701 |
Margareth R.C. Marques, Ph.D.
Senior Scientific Liaison 1-301-816-8106 |
(GCDF2010) General Chapters - Dosage Forms |
| 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 2106
Pharmacopeial Forum: Volume No. 36(4) Page 890