Prednisolone Sodium Phosphate
(pred nis' oh lone soe' dee um fos' fate).
C21H27Na2O8P
484.39
484.39Pregna-1,4-diene-3,20-dione, 11,17-dihydroxy-21-(phosphonooxy)-, disodium salt, (11
)-.
11
,17,21-Trihydroxypregna-1,4-diene-3,20-dione 21-(disodium phosphate)
[125-02-0].» Prednisolone Sodium Phosphate contains not less than 96.0 percent and not more than 102.0 percent of C21H27Na2O8P, calculated on the anhydrous basis.
Packaging and storage—
Preserve in tight containers.
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Identification—
B:
The residue from the ignition of about 20 mg of it meets the requirements of the tests for Sodium 
191
and for Phosphate 191.
191 and for Phosphate 191.
Specific rotation 781S:
between +95
and +102.
781S:
between +95 and +102.
Test solution:
10 mg per mL, in a mixture of pH 7.0 phosphate buffer and carbon dioxide-free water (9:1).
pH 791:
between 7.5 and 10.5, in a solution (1 in 100).
791:
between 7.5 and 10.5, in a solution (1 in 100).
Water, Method I 921:
not more than 6.5%.
921:
not more than 6.5%.
Phosphate ions—
Standard phosphate solution—
Dissolve 143.3 mg of dried monobasic potassium phosphate, KH2PO4, in water to make 1000.0 mL. This solution contains the equivalent of 0.10 mg of phosphate (PO4) in each mL.
Phosphate reagent A—
Dissolve 5 g of ammonium molybdate in 1 N sulfuric acid to make 100 mL.
Phosphate reagent B—
Dissolve 350 mg of p-methylaminophenol sulfate in 50 mL of water, add 20 g of sodium bisulfite, mix to dissolve, and dilute with water to 100 mL.
Procedure—
Dissolve about 50 mg of Prednisolone Sodium Phosphate, accurately weighed, in a mixture of 10 mL of water and 5 mL of 2 N sulfuric acid contained in a 25-mL volumetric flask, by warming if necessary. Add 1 mL each of Phosphate reagent A and Phosphate reagent B, dilute with water to 25 mL, mix, and allow to stand at room temperature for 30 minutes. Similarly and concomitantly, prepare a standard solution, using 5.0 mL of Standard phosphate solution instead of the 50 mg of the substance under test. Concomitantly determine the absorbances of both solutions in 1-cm cells at 730 nm, with a suitable spectrophotometer, using water as the blank. The absorbance of the test solution is not more than that of the standard solution. The limit is 1.0% of phosphate (PO4).
Selenium 291:
0.003%, a 200-mg test specimen being used.
291:
0.003%, a 200-mg test specimen being used.
Related compounds—
Buffer solution, Mobile phase, and System suitability solution—
Proceed as directed in the Assay.
Standard solution—
Accurately weigh a known quantity of USP Prednisolone Sodium Phosphate RS into an appropriate volumetric flask. Dilute quantitatively, and stepwise if necessary, with Mobile phase to obtain a solution having a known concentration of about 0.001 mg per mL.
Test solution—
Accurately weigh a known quantity of Prednisolone Sodium Phosphate into an appropriate volumetric flask. Dilute quantitatively, and stepwise if necessary, with Mobile phase to obtain a solution having a known concentration of about 1 mg per mL.
Chromatographic system (see Chromatography 621)—
Proceed as directed in the Assay . The run time is about four times the retention time of prednisolone sodium phosphate.
621)—
Proceed as directed in the Assay . The run time is about four times the retention time of prednisolone sodium phosphate.
Procedure—
Inject equal volumes (about 20 µL) of the Standard solution and the Test solution into the chromatograph, record the chromatograms, and measure the peak responses. Calculate the percentage of the individual impurities listed in Table 1 in the portion of Prednisolone Sodium Phosphate taken by the formula:
(100/F)(CS / CT)(rT / rS)
in which F is the relative response factor (see Table 1 for values); CS is the concentration, in mg per mL, of USP Prednisolone Sodium Phosphate RS in the Standard solution; CT is the concentration, in mg per mL, of Prednisolone Sodium Phosphate in the Test solution; rT is the peak response of each individual impurity in the Test solution; and rS is the peak response of the prednisolone sodium phosphate in the Standard solution. The percentage limit of each individual impurity is given in Table 1.
Table 1
| Component | Relative Retention Time |
Relative Response Factor |
Limit (%) |
|---|---|---|---|
| Impurity A1 | 0.18 | 1 | NMT 0.2 |
| Impurity B2 | 0.29 | 1 | NMT 1.0 |
| d-homo A derivative3 | 0.40 | 1 | NMT 1.0 |
| Prednisolone (free)4 | 0.54 | 1.3 | NMT 1.0 |
| D-homo B derivative5 | 0.72 | 1 | NMT 1.0 |
| Prednisone sodium phosphate | 0.77 | 1.0 | NMT 0.5 |
| Impurity C6 | 0.85 | 1 | NMT 0.3 |
| Impurity D7 | 0.94 | 1 | NMT 0.2 |
| Impurity E8 | 2.72 | 1 | NMT 0.5 |
| Impurity F9 | 3.50 | 1 | NMT 0.2 |
| Any other individual unspecified impurity | — | 1 | NMT 0.1 |
| Total of all impurities | — | — | NMT 3.0 |
|
1
11
,17,20-Trihydroxy-21-nor-13(17)a-homopregnane-1,4-diene-3,13a-dione 20-phosphate.
2
11
,17 -Dihydroxyandrosta-1,4-diene-3-one 17-carboxylic acid.
3
11
,17,20-Trihydroxy-21-nor-14(15)a-homopregnane-1,4-diene-3,16-dione 20-phosphate.
4
11
,17,21-Trihydroxypregna-1,4-diene-3,20-dione.
5
11
,17,20-Trihydroxy-21-nor-14(15)a-homopregnane-1,4-diene-3,16-dione 20-phosphate.
6
21-Oxo-11
,17,21-trihydroxypregna-1,4-diene-3,20-dione.
7
11
-Hydroxyandrosta-1,4-diene-3,17-dione.
8
16
-Phosphoryloxyacetyl-11,16-dihydroxyandrosta-1,4-diene-3-one 11-phosphate.
9
21-Oxo-20-phosphoryloxy-11
-hydroxypregna-1,4,17-triene-3-one.
|
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Assay—
Mobile phase—
Transfer 6.6 g of hexylamine and 5.32 g of monobasic ammonium phosphate into an appropriate flask. After 10 minutes, add 1850 g of water and dissolve the contents while stirring. Adjust with phosphoric acid to a pH of 6.40 ± 0.05. Add 390 g of acetonitrile, mix by stirring, and then sonicate for not more than 2 minutes.
System suitability solution—
Dissolve equal, accurately weighed, quantities of USP Prednisolone RS and USP Prednisolone Sodium Phosphate RS in Mobile phase to obtain a solution having a known concentration of about 0.01 mg per mL of each of the Reference Standards.
Standard preparation—
Dissolve an accurately weighed quantity of USP Prednisolone RS in Mobile phase to obtain a solution having a known concentration of about 0.3 mg per mL.
Assay preparation—
Dissolve an accurately weighed quantity of the Prednisolone Sodium Phosphate in Mobile phase to obtain a solution having a known concentration of about 0.42 mg per mL.
Chromatographic system (see Chromatography 621)—
The liquid chromatograph is equipped with a 254-nm detector and a 4.6-mm × 7.5-cm column that contains 3.5-µm packing L1. The column temperature is maintained at 35, and the injector temperature is maintained at 6. The flow rate is about 1.5 mL per minute, and the run time is about 22 minutes. Chromatograph the System suitability solution, and record the peak responses as directed for Procedure: the relative retention times are about 0.52 for prednisolone and 1 for prednisolone sodium phosphate; the resolution, R, between prednisolone and prednisolone sodium phosphate is not less than 12; and the relative standard deviation for five replicate injections of the Standard preparation is not more than 1.0%.
621)—
The liquid chromatograph is equipped with a 254-nm detector and a 4.6-mm × 7.5-cm column that contains 3.5-µm packing L1. The column temperature is maintained at 35, and the injector temperature is maintained at 6. The flow rate is about 1.5 mL per minute, and the run time is about 22 minutes. Chromatograph the System suitability solution, and record the peak responses as directed for Procedure: the relative retention times are about 0.52 for prednisolone and 1 for prednisolone sodium phosphate; the resolution, R, between prednisolone and prednisolone sodium phosphate is not less than 12; and the relative standard deviation for five replicate injections of the Standard preparation is not more than 1.0%.
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 C21H27Na2O8P in the portion of the Prednisolone Sodium Phosphate taken using the formula:
100(CS / CU)(484.39/360.45)(rU / rS)
in which CS and CU are the concentrations, in mg per mL, of prednisolone in the Standard preparation and Prednisolone Sodium Phosphate in the Assay preparation, respectively; 484.39 and 360.45 are the molecular weights for prednisolone sodium phosphate and free prednisolone, respectively; and rU and rS are the peak responses obtained from the Assay preparation and the Standard preparation, respectively.
Auxiliary Information—
Please check for your question in the FAQs before contacting USP.
| Topic/Question | Contact | Expert Committee |
|---|---|---|
| Monograph | Mary S. Waddell
Scientific Liaison 1-301-816-8124 |
(SM42010) Monographs - Small Molecules 4 |
| Reference Standards | RS Technical Services 1-301-816-8129 rstech@usp.org |
USP35–NF30 Page 4403
Pharmacopeial Forum: Volume No. 34(1) Page 108