Alprazolam Tablets
DEFINITION
Alprazolam Tablets contain NLT 90.0% and NMT 110.0% of the labeled amount of alprazolam (C17H13ClN4).
IDENTIFICATION
• A. Infrared Absorption
Sample:
An amount of finely powdered Tablets, equivalent to 15 mg of alprazolam, prepared as follows. Dissolve the Sample in 10 mL of 10 mg/mL of sodium carbonate solution. Add 15 mL of chloroform, and shake vigorously for 30 min. Centrifuge, withdraw the aqueous layer, and transfer the chloroform to a clean container. Add 200 mg of potassium bromide. Evaporate the chloroform from this mixture to dryness, and dry the dispersion in vacuum at 60
for 24 h. Grind this dispersion into a fine powder. Prepare a suitable pellet for testing by placing 100 mg of dried potassium bromide into a die. Sprinkle 20 mg of the finely ground alprazolam–potassium bromide dispersion onto the dried potassium bromide layer, and cover with another specimen of 100 mg of dried potassium bromide.
for 24 h. Grind this dispersion into a fine powder. Prepare a suitable pellet for testing by placing 100 mg of dried potassium bromide into a die. Sprinkle 20 mg of the finely ground alprazolam–potassium bromide dispersion onto the dried potassium bromide layer, and cover with another specimen of 100 mg of dried potassium bromide.
Acceptance criteria:
The IR absorption spectrum of the potassium bromide dispersion so obtained exhibits maxima characteristic of alprazolam, as compared to that of a similar preparation of USP Alprazolam RS, at the following wavenumbers: at 1609, 1578, 1566, 1539, 1487, and 1379 wavenumbers in the region of 1650–1300 cm
1; at 932, 891, 826, 779, 746, 696, and 658 wavenumbers in the region of 975–600 cm1.
1; at 932, 891, 826, 779, 746, 696, and 658 wavenumbers in the region of 975–600 cm1.
ASSAY
• Procedure
Mobile phase:
Acetonitrile, chloroform, butyl alcohol, glacial acetic acid, and water (850: 80: 50: 0.5: 20)
Internal standard solution:
0.25 mg/mL of triazolam in acetonitrile
Standard stock solution:
0.25 mg/mL of USP Alprazolam RS in Internal standard solution
Standard solution:
25 µg/mL of USP Alprazolam RS from Standard stock solution in acetonitrile
Sample solution:
Nominally 25 µg/mL of alprazolam from finely powdered Tablets (NLT 20) prepared as follows. Transfer a suitable amount of the powdered tablets to a suitable volumetric flask. Add 1% of the flask volume of water. Transfer 10% of the flask volume of Internal standard solution, shake vigorously for 10 min, and dilute with acetonitrile to volume.
Chromatographic system
Mode:
LC
Detector:
UV 254 nm
Column:
4.6-mm × 30-cm; packing L3
Flow rate:
2 mL/min
Injection size:
20 µL
System suitability
Sample:
Standard solution
Suitability requirements
Resolution:
NLT 2.0 between triazolam and alprazolam
Relative standard deviation:
NMT 2.0% for replicate injections
Analysis
Samples:
Standard solution and Sample solution
Calculate the percentage of the labeled amount of alprazolam (C17H13ClN4) in the portion of Tablets taken:
Result = (RU/RS) × (CS/CU) × 100
| RU | = | = peak area response ratio of the alprazolam peak relative to the internal standard peak from the Sample solution |
| RS | = | = peak area response ratio of the alprazolam peak relative to the internal standard peak 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
• Dissolution, Procedure for a Pooled Sample 
711
711
Buffer stock solution:
Dissolve 80 g of monobasic potassium phosphate and 20 g of dibasic potassium phosphate in 1 L of water. Add, with mixing, phosphoric acid or potassium hydroxide solution (45 in 100), as necessary to adjust the solution, such that the resulting solution has a pH of 6.0 ± 0.1.
Buffer:
Prepare a 1-in-10 dilution of the Buffer stock solution to obtain a solution that has a pH of 6.0 ± 0.1.
Medium:
Buffer; 500 mL
Apparatus 1:
100 rpm
Time:
30 min
Mobile phase:
Acetonitrile, tetrahydrofuran, and Buffer (35:5:60)
Standard stock solution:
0.05 mg/mL of USP Alprazolam RS in methanol
Standard solution:
Add 50 mL of Buffer stock solution and 250 mL of water to a 500-mL flask. Add to the flask 5.0 mL of Standard stock solution for every 0.25 mg of alprazolam contained in the Tablet being assayed. Dilute with water to volume.
Sample solution:
Pass a portion of the solution under test through a suitable filter.
Chromatographic system
Mode:
LC
Detector:
UV 254 nm
Column:
4.6-mm × 10-cm; packing L7
Flow rate:
1 mL/min
System suitability
Sample:
Standard solution
Suitability requirements
Column efficiency:
NLT 500 theoretical plates
Relative standard deviation:
NMT 3.0% for replicate injections
Analysis
Samples:
Standard solution and Sample solution
Calculate the percentage of labeled amount of alprazolam (C17H13ClN4) dissolved.
Tolerances:
NLT 80% (Q) of the labeled amount of alprazolam (C17H13ClN4) is dissolved.
• Uniformity of Dosage Units 905
905
Mobile phase, Chromatographic system, and System suitability:
Proceed as directed in the Assay.
Internal standard solution
0.032 mg/mL of triazolam in acetonitrile
Standard solution:
0.025 mg/mL of USP Alprazolam RS in Internal standard solution
Sample solution:
Transfer 1 Tablet to a container. Add 0.4 mL of water directly onto the Tablet, allow the Tablet to stand for 2 min, and then swirl the container to disperse the Tablet. For every 0.25 mg of alprazolam contained in the Tablet, add 10.0 mL of Internal standard solution to the container. Shake, and centrifuge if necessary.
Analysis
Samples:
Standard solution and Sample solution
Calculate the percentage of alprazolam (C17H13ClN4) in the Tablet taken:
Result = (RU/RS) × C × V × (100/L)
| RU | = | = peak area response ratio of the alprazolam peak relative to the internal standard peak from the Sample solution |
| RS | = | = peak area response ratio of the alprazolam peak relative to the internal standard peak from the Standard solution |
| C | = | = concentration of USP Alprazolam RS in the Standard solution (mg/ml) |
| V | = | = volume of Internal standard solution used to prepare the Sample solution (mL) |
| L | = | = label claim (mg/Tablet) |
Acceptance criteria:
Meet the requirements
ADDITIONAL REQUIREMENTS
• Packaging and Storage:
Preserve in tight, light-resistant containers, and store at controlled room temperature.
• USP Reference Standards 11
11
USP Alprazolam RS 
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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 |
| 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 2104
Pharmacopeial Forum: Volume No. 33(1) Page 41