Identification—
A:
Infrared Absorption 
197
—The spectra of trifluorovinyl chloride polymer and mineral oil dispersions of it, separately prepared from a test specimen recrystallized from water and dried at 105
for 1 hour, exhibit maxima in the regions of 4000 to 1350 cm
1 and 1350 to 450 cm
1, respectively, only at the same wavelengths as those of similar preparations of
USP Etidronate Disodium RS.
B:
A solution (1 in 100) responds to the flame test for
Sodium 191.
Limit of phosphite—
Solution A—
Prepare an aqueous solution containing 0.65 mg per mL of anhydrous sodium carbonate and 0.40 mg per mL of sodium bicarbonate.
Solution B—
Prepare an aqueous solution containing 4.68 mg per mL of anhydrous sodium carbonate and 2.89 mg per mL of sodium bicarbonate.
Mobile phase—
Use variable mixtures of
Solution A and
Solution B as directed for
Chromatographic system. Make adjustments if necessary (see
System Suitability under
Chromatography 621).
Standard solution—
Dissolve suitable quantities of
USP Etidronate Disodium Related Compound A RS and dibasic sodium phosphate in
Solution A to obtain a solution having a known concentration of 0.027 mg of sodium phosphite dibasic pentahydrate and 0.015 mg of dibasic sodium phosphate in each mL.
[NOTE—Etidronate Disodium Related compound A is sodium phosphite dibasic pentahydrate.
]
Suppressor regenerant solution—
Use 12.5 mM sulfuric acid.
Test solution—
Transfer approximately 50 mg of Etidronate Disodium, accurately weighed, to a suitable flask. Dissolve in 10.0 mL of Solution A.
Chromatographic system (see Chromatography 621)—
The liquid chromatograph is equipped with a conductivity detector, a 4-mm × 25-cm column and a 4-mm × 50-mm guard column that contain packing L61 and a 4-mm anion self-regenerating suppressor. The flow rate is about 1.0 mL per minute for the
Mobile phase and 3 to 5 mL per minute for the
Suppressor regenerant solution. The chromatograph is programmed as follows.
Time
(minutes) |
Solution A
(%) |
Solution B
(%) |
 Elution |
| 0–6.0 |
100 |
0 |
isocratic |
| 6.0–6.1 |
100®0 |
0®100 |
linear gradient |
| 6.1–8.0 |
0 |
100 |
isocratic |
| 8.0–8.1 |
0 ®100 |
100®0 |
linear gradient |
| 8.1–15 |
100 |
0 |
isocratic |
Chromatograph the
Standard solution, and record the peak responses as directed for
Procedure: the elution order is phosphite, followed by phosphate; the resolution,
R, between phosphite and phosphate is not less than 2.5; and the relative standard deviation for replicate injections is not more than 10% for each peak.
Procedure—
Separately inject equal volumes (about 20 µL) of the
Standard solution and the
Test solution into the chromatograph, record the chromatograms, and measure the responses for the phosphite peaks. Calculate the percentage of phosphite, determined as monobasic sodium phosphite, in the portion of Etidronate Disodium taken by the formula:
1000(103.98/216.06)(C/W)(rU / rS),
in which 103.98 and 216.06 are the molecular weights of sodium phosphite monobasic and sodium phosphite dibasic pentahydrate, respectively;
C is the concentration, in mg per mL, of
USP Etidronate Disodium Related Compound A RS in the
Standard solution; W is the weight, in mg, of Etidronate Disodium taken to prepare the
Test solution; and
rU and
rS are the phosphite peak responses obtained from the
Test solution and the
Standard solution, respectively: not more than 1.0% of phosphite, determined as monobasic sodium phosphite, is found.
Heavy metals, Method II 231—
Use 0.5 g of Etidronate Disodium for the
Test Preparation and 2.5 mL of
Standard Lead Solution for the
Standard Preparation. Transfer the
Test Preparation and the
Standard Preparation to separate quartz crucibles, add 0.5 g of magnesium oxide to each crucible, and mix. Evaporate the
Standard Preparation to dryness at 110
for 1 hour, and ignite each crucible over a flame to a light gray color. Ignite at 800
for 1 hour, cool, and dissolve the residues by the dropwise addition of hydrochloric acid, and add 3 mL of water. Adjust with ammonia TS to a pH of 8.5, then adjust with acetic acid to a pH of 4. Make a final pH adjustment to 3.4 ± 0.05, using dilute hydrochloric acid. Filter into 50-mL color comparison tubes, and dilute with water to 40 mL. The limit is 0.005%.
Assay—
Mobile phase—
Prepare a 35 mM to 40 mM ammonium nitrate solution in water, and adjust with dilute ammonium hydroxide to a pH of 7.0.
Standard preparation—
Dissolve an accurately weighed quantity of
USP Etidronic Acid Monohydrate RS in a mixture of 1 mL of 1 N sodium hydroxide solution and 150 mL of
Mobile phase, to obtain a solution having a known concentration of between 0.73 and 0.75 mg of etidronic acid monohydrate per mL.
Assay preparation—
Transfer between 42.0 and 43.0 mg of Etidronate Disodium, accurately weighed, to a 50-mL volumetric flask, and dissolve in and dilute with Mobile phase to volume.
Chromatographic system (see Chromatography 621)—
The liquid chromatograph is equipped with a refractive index detector and a 4.6 × 150-mm column that contains packing L23. The column and the detector temperatures are maintained at 32
. The flow rate is about 1.5 mL per minute. Chromatograph the
Standard preparation, and record the peak responses as directed for
Procedure: the relative standard deviation for replicate injections is not more than 1.5%.
Procedure—
Separately inject equal volumes (about 20 µL) of the
Standard preparation and the
Assay preparation into the chromatograph, record the chromatograms, and measure the responses for the major peaks. Calculate the percentage of C
2H
6Na
2O
7P
2 in the portion of Etidronate Disodium taken by the formula:
100(250.00/224.05)(CS / CU)(rU / rS),
in which 250.00 and 224.05 are the molecular weights of etidronate disodium and etidronic acid monohydrate, respectively;
CS is the concentration, in mg per mL, of
USP Etidronic Acid Monohydrate RS in the
Standard preparation; CU is the concentration, in mg per mL, of Etidronate Disodium in the
Assay preparation; and
rU and
rS are the peak responses obtained from the
Assay preparation and the
Standard preparation, respectively.
;)
