Alendronate Sodium Tablets
DEFINITION
Alendronate Sodium Tablets contain an amount of Alendronate Sodium equivalent to NLT 90.0% and NMT 110.0% of the labeled amount of alendronic acid (C4H13NO7P2).
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
Solution A:
14.7 g/L of sodium citrate dihydrate and 7.05 g/L of anhydrous dibasic sodium phosphate in water. [Note—Adjust with phosphoric acid to a pH of 8.0 before bringing the solution to volume. ]
Solution B:
38.1 g/L of sodium borate in water
Solution C:
1 mg/mL of 9-fluorenylmethyl chloroformate in acetonitrile. [Note—Prepare this solution fresh just before use. ]
Mobile phase:
Acetonitrile, methanol, and Solution A (20:5:75)
Diluent:
29.4 g/L of sodium citrate dihydrate in water
Standard stock solution:
0.03 mg/mL of anhydrous alendronate sodium in Diluent, from USP Alendronate Sodium RS
Standard solution:
Transfer 5.0 mL of the Standard stock solution to a 50-mL polypropylene screw-cap centrifuge tube containing 5 mL of Solution B, and mix for 3 min. Add 4 mL of Solution C, and agitate for 30 s. Allow the solution to stand at room temperature for 25 min. Add 25 mL of methylene chloride, and agitate for 40 s. Centrifuge the mixture for 10 min. Use the clear upper aqueous layer.
Sample stock solution:
Transfer NLT 10 Tablets to a 1000-mL volumetric flask. Add 500 mL of Diluent, shake by mechanical means for 30 min, and sonicate for 5 min. Dilute with Diluent to volume, and centrifuge a portion of this solution. Quantitatively dilute a portion of the clear supernatant to a concentration of 0.02–0.03 mg/mL of alendronic acid.
Sample solution:
Transfer 5.0 mL of the Sample stock solution to a 50-mL polypropylene screw-cap centrifuge tube containing 5 mL of Solution B, and mix for 3 min. Add 4 mL of Solution C, and agitate for 30 s. Allow the solution to stand at room temperature for 25 min. Add 25 mL of methylene chloride, and agitate for 40 s. Centrifuge the mixture for 10 min. Use the clear upper aqueous layer.
Blank:
Transfer 5 mL of Diluent to a 50-mL polypropylene screw-cap centrifuge tube containing 5 mL of Solution B, and mix for 3 min. Add 4 mL of Solution C, and agitate for 30 s. Allow the solution to stand at room temperature for 25 min. Add 25 mL of methylene chloride, and agitate for 40 s. Centrifuge the mixture for 10 min. Use the clear upper aqueous layer.
Chromatographic system
Mode:
LC
Detector:
UV 266 nm
Column:
4.1-mm × 25-cm; packing L21
Column temperature:
35
Flow rate:
1 mL/min
Injection size:
50 µL
System suitability
Sample:
Standard solution
Suitability requirements
Capacity factor:
NLT 2.0
Relative standard deviation:
NMT 2.0% for replicate injections
Analysis
Samples:
Standard solution, Sample solution, and Blank
Calculate the percentage of the label claim in the portion of C4H13NO7P2 taken:
Result = (rU/rS) × (CS/CU) × (Mr1/Mr2) × 100
| rU | = | = peak area from the Sample solution |
| rS | = | = peak area from the Standard solution |
| CS | = | = concentration of anhydrous USP Alendronate Sodium RS in the Standard stock solution (mg/mL) |
| CU | = | = nominal concentration of alendronic acid in the Sample stock solution (mg/mL) |
| Mr1 | = | = molecular weight of alendronic acid, 249.10 |
| Mr2 | = | = molecular weight of anhydrous alendronate sodium, 271.09 |
Acceptance criteria:
C4H12NNaO7P2 equivalent to 90.0%–110.0% of the labeled amount of C4H13NO7P2
PERFORMANCE TESTS
• Dissolution 
711
711
Test 1
Medium:
Water; 900 mL
Apparatus 2:
50 rpm
Time:
15 min
Determine the amount of C4H13NO7P2 dissolved by using the following method.
Solution A and Mobile phase:
Proceed as directed in the Assay.
Diluent:
176.4 g/L of sodium citrate in Medium
Solution B:
Dissolve 6.2 g of boric acid in approximately 950 mL of water. Adjust with 1 N sodium hydroxide to a pH of 9.0, and dilute with water to 1 L.
Solution C:
0.5 mg/mL of 9-fluorenylmethyl chloroformate in acetonitrile. [Note—Prepare this solution fresh. ]
Standard stock solution:
USP Alendronate Sodium RS in Medium to make a concentration equivalent to dissolving 1 Tablet in 900 mL of the same Medium. Calculate the concentration, C (mg/mL), of anhydrous alendronate sodium in this solution.
Standard solution:
Transfer 5.0 mL of the Standard stock solution to a 50-mL polypropylene screw-cap centrifuge tube containing 1.0 mL of Diluent and 5.0 mL of Solution B, and mix for 3 min. Add 4.0 mL of Solution C, and agitate for 30 s. Allow the solution to stand at room temperature for 25 min. Add 25 mL of methylene chloride, and agitate for 40 s. Centrifuge the mixture for 5 min. Use a portion of the clear, upper aqueous layer.
Blank:
Transfer 5 mL of water to a 50-mL polypropylene screw-cap centrifuge tube containing 1.0 mL of Diluent and 5.0 mL of Solution B, and mix for 3 min. Add 4.0 mL of Solution C, and agitate for 30 s. Allow the solution to stand at room temperature for 25 min. Add 25 mL of methylene chloride, and agitate for 40 s. Centrifuge the mixture for 5 min. Use a portion of the clear, upper aqueous layer.
Sample solution:
Withdraw a portion of the solution under test, and centrifuge immediately. Transfer 5.0 mL of the supernatant to a 50-mL polypropylene screw-cap centrifuge tube containing 1.0 mL of Diluent and 5.0 mL of Solution B, and mix for 3 min. Add 4.0 mL of Solution C, and agitate for 30 s. Allow the solution to stand at room temperature for 25 min. Add 25 mL of methylene chloride, and agitate for 40 s. Centrifuge the mixture for 5 min. Use a portion of the clear, upper aqueous layer.
Chromatographic system and System suitabilitity:
Proceed as directed in the Assay.
Analysis
Samples:
Standard solution and Sample solution
Calculate the percentage of C4H13NO7P2 dissolved:
Result = (rU/rS) × C × (Mr1/Mr2) × V × (100/L)
| rU | = | = peak area from the Sample solution |
| rS | = | = peak area from the Standard solution |
| C | = | = defined under the Standard stock solution |
| Mr1 | = | = molecular weight of alendronic acid, 249.10 |
| Mr2 | = | = molecular weight of alendronate sodium, 271.09 |
| V | = | = volume of the Medium, 900 mL |
| L | = | = Tablet label claim (mg) |
Tolerances:
NLT 80% (Q) of the labeled amount of C4H13NO7P2 is dissolved; for tablets labeled for weekly dosing, NLT 75% (Q) of the labeled amount of C4H13NO7P2 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:
50 rpm
Time:
30 min
Determine the amount of C4H12NNaO7P2·3H2O dissolved using the following method.
Solution B and Solution C:
Proceed as directed in the Assay.
0.6 M citrate buffer:
176.4 g/L of sodium citrate dihydrate in water
0.05 M buffer:
Transfer 14.7 g of sodium citrate dihydrate and 7.05 g of anhydrous dibasic sodium phosphate to a 1000-mL volumetric flask, dissolve in about 900 mL of water, adjust with phosphoric acid to a pH of 8.0, and dilute with water to volume.
Mobile phase:
0.05 M buffer, acetonitrile, and methanol (76:19:5)
Standard stock solution:
Prepare a solution of USP Alendronate Sodium RS in Medium with a final concentration corresponding to the concentration obtained by dissolving 1 tablet in 900 mL of Medium. Calculate the concentration, C (mg/mL), of anhydrous alendronate sodium in this solution.
Standard solution:
Transfer 5.0 mL of the Standard stock solution to a 50-mL screw-cap polypropylene centrifuge tube containing 1.0 mL of 0.6 M citrate buffer and 5.0 mL of Solution B, and mix for about 3 min. Add 4.0 mL of Solution C, and agitate for about 30 s. Allow the solution to stand at room temperature for about 30 min. Add 25 mL of methylene chloride, and agitate vigorously for about 40 s. Centrifuge the mixture for 10 min. Use a portion of the clear upper aqueous layer.
Blank:
Using 5 mL of water, proceed as directed for the Standard solution, beginning with “to a 50-mL screw-cap polypropylene centrifuge tube”.
Sample solution
For Tablets labeled to contain 5 mg, 10 mg, 35 mg, or 40 mg:
After 30 min, withdraw 30 mL of the solution under test, and pass through a suitable 0.45-µm filter, discarding the first 10 mL. Using 5.0 mL of the filtrate, proceed as directed for the Standard solution, beginning with “to a 50-mL screw-cap polypropylene centrifuge tube”.
For Tablets labeled to contain 70 mg:
After 30 min, withdraw 30 mL of the solution under test, and pass through a suitable 0.45-µm filter, discarding the first 10 mL. Transfer 6.0 mL of the filtrate to a 10-mL volumetric flask, and dilute with water to volume. Using 5.0 mL of this dilution, proceed as directed for the Standard solution, beginning with “to a 50-mL screw-cap polypropylene centrifuge tube”.
Chromatographic system and System suitability:
Proceed as directed in the Assay.
Analysis:
Proceed as directed in Test 1.
Tolerances:
NLT 80% (Q) of the labeled amount of alendronate sodium (C4H12NNaO7P2·3H2O) is dissolved.
• Uniformity of Dosage Units 905:
Meet the requirements
905:
Meet the requirements
ADDITIONAL REQUIREMENTS
• Packaging and Storage:
Preserve in tight containers. Store between 15 and 30.
and 30.
• Labeling:
The labeling indicates weekly dosing where appropriate. When more than one Dissolution test is given, the labeling states the test used only if Test 1 is not used.
• USP Reference Standards 11
11
USP Alendronate Sodium RS 
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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 2094
Pharmacopeial Forum: Volume No. 36(5) Page 1157