Oxaliplatin for Injection
DEFINITION
Oxaliplatin for Injection is a sterile, lyophilized mixture of Oxaliplatin and Lactose Monohydrate. It contains NLT 90.0% and NMT 110.0% of the labeled amount of oxaliplatin (C8H14N2O4Pt).
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
[Note—Use vigorous shaking and very brief sonication to dissolve the substance to be examined. Inject the Sample solution within 20 min of preparation. Use polypropylene HPLC autosampler vials. ]
Acidified water:
Adjust water with phosphoric acid to a pH of 3.0.
Mobile phase:
Acetonitrile and Acidified water (1:99)
System suitability solution:
0.1 mg/mL each of USP Oxaliplatin RS and USP Oxaliplatin System Suitability RS in water. [Note—USP Oxaliplatin System Suitability RS is compound [SP-4-2-(1R-trans)]-(1,2-cyclohexanediamine-N,N¢) dichloridoplatinum(II). ]
Standard solution:
0.1 mg/mL of USP Oxaliplatin RS in water
Sample solution:
Constitute a suitable number of vials of Oxaliplatin for Injection with the appropriate amount of water to obtain a solution having a known concentration of about 0.1 mg/mL of oxaliplatin, based on the label claim.
Chromatographic system
Mode:
LC
Detector:
UV 210 nm
Column:
4.6-mm × 25-cm; 5-µm packing L1
Column temperature:
40
Flow rate:
1.2 mL/min
Injection size:
20 µL
System suitability
Samples:
System suitability solution and Standard solution
[Note—The relative retention times for USP Oxaliplatin System Suitability RS and oxaliplatin are about 0.9 and 1.0, respectively. ]
Suitability requirements
Resolution:
NLT 2.0 between the peaks of USP Oxaliplatin System Suitability RS and oxaliplatin, System suitability solution
Tailing factor:
NMT 2.0 for the oxaliplatin peak, System suitability solution
Relative standard deviation:
NMT 1.0%, Standard solution
Analysis
Samples:
Standard solution and Sample solution
Calculate the percentage of the labeled amount of oxaliplatin (C8H14N2O4Pt) in the portion of Oxaliplatin for Injection 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 Oxaliplatin RS in the Standard solution (mg/mL) |
| CU | = | = nominal concentration of oxaliplatin in the Sample solution (mg/mL) |
Acceptance criteria:
90.0%–110.0%
PERFORMANCE TESTS
• Uniformity of Dosage Units 
905
:
Meets the requirements
905:
Meets the requirements
IMPURITIES
• Limit of Oxalic Acid
[Note—Use vigorous shaking and very brief sonication to dissolve the substance to be examined. Inject the Sample solution within 20 min of preparation. Use polypropylene HPLC autosampler vials. ]
Buffer:
Add 1.36 g of potassium dihydrogen phosphate to 10 mL of 10% tetrabutylammonium hydroxide in water, and dilute with water to 1000 mL. Adjust with phosphoric acid to a pH of 6.0.
Mobile phase:
Acetonitrile and Buffer (1:4)
Standard stock solution:
0.06 mg/mL of USP Oxaliplatin Related Compound A RS in water. [Note—USP Oxaliplatin Related Compound A RS is available as oxalic acid dihydrate. ]
Standard solution:
15 µg/mL of USP Oxaliplatin Related Compound A RS in water, from the Standard stock solution
System suitability stock solution:
0.05 mg/mL of sodium nitrate in water
System suitability solution:
1.0 µg/mL of sodium nitrate and 15 µg/mL of oxaliplatin related compound A in water, from the System suitability stock solution and Standard stock solution, respectively
Sensitivity solution:
Make a 1-to-10 dilution of the Standard solution in water.
Sample solution:
2.0 mg/mL of oxaliplatin in water from Oxaliplatin for Injection
Chromatographic system
Mode:
LC
Detector:
UV 205 nm
Column:
4.6-mm × 25-cm; 5-µm packing L1
Column temperature:
40
Flow rate:
2 mL/min
Injection size:
20 µL
System suitability
Samples:
Standard solution, System suitability solution, and Sensitivity solution
[Note—The relative retention times for sodium nitrate and oxalic acid are about 0.6 and 1.0, respectively. ]
Suitability requirements
Resolution:
NLT 2.0 between oxalic acid and sodium nitrate, System suitability solution
Relative standard deviation:
NMT 3.0% for the oxalic acid peak, Standard solution
Sensitivity:
The signal-to-noise ratio of the peak at approximately the same retention time as that in the Standard solution is NLT 10, Sensitivity solution.
Analysis
Samples:
Standard solution and Sample solution
Calculate the percentage of oxalic acid in the portion of Oxaliplatin for Injection taken:
Result = (rU/rS) × (CS/CU) × (Mr1/Mr2) × 100
| rU | = | = peak response of oxalic acid from the Sample solution |
| rS | = | = peak response of oxalic acid from the Standard solution |
| CS | = | = concentration of USP Oxaliplatin Related Compound A RS in the Standard solution (mg/mL) |
| CU | = | = concentration of oxaliplatin in the Sample solution (mg/mL) |
| Mr1 | = | = molecular weight of anhydrous oxalic acid, 90.03 |
| Mr2 | = | = molecular weight of USP Oxaliplatin Related Compound A RS, 126.07 |
Acceptance criteria:
NMT 0.5%
• Limit of (SP-4-2)-Diaqua[(1R,2R)-cyclohexane-1,2-diamine-N,N¢]platinum
[Note—Use vigorous shaking and very brief sonication to dissolve the substance to be examined. Inject the Sample solution within 20 min of preparation. Use polypropylene HPLC autosampler vials. ]
Buffer:
Dissolve 1.36 g of potassium dihydrogen phosphate and 1 g of sodium 1-heptanesufonate in 1 L of water. Adjust with phosphoric acid to a pH of 3.0.
Mobile phase:
Acetonitrile and Buffer (1:4)
System suitability solution:
2 mg/mL of USP Oxaliplatin RS in 0.005 M sodium hydroxide. Allow this solution to stand at room temperature for at least 5 days. [Note—Sonicate if necessary. ] Transfer 5 mL of this solution into a 50-mL volumetric flask, and dilute with water to volume. [Note—The preparation of the System suitability solution forms diaquodiaminocyclohexaneplatinum dimer and (SP-4-2)-diaqua[(1R,2R)-cyclohexane-1,2-diamine-N,N¢]platinum. ]
Standard solution:
Transfer USP Oxaliplatin Related Compound B RS to a suitable volumetric flask, add 25% of the final volume of methanol, and sonicate for approximately 30 min to dissolve. Allow to cool if necessary, and dilute with water to volume to obtain a solution having a known concentration of about 0.0125 mg/mL. [Note—When preparing the solution, USP Oxaliplatin Related Compound B RS is converted to (SP-4-2)-diaqua[(1R,2R)-cyclohexane-1,2-diamine-N,N¢]platinum. ]
Sample solution:
Use the Sample solution from the test for Limit of Oxalic Acid.
Chromatographic system
Mode:
LC
Detector:
UV 215 nm
Column:
4.6-mm × 25-cm; 5-µm packing L1
Column temperature:
40
Flow rate:
2 mL/min
Injection size:
20 µL
System suitability
Samples:
System suitability solution and Standard solution
[Note—The relative retention times for (SP-4-2)-diaqua[(1R,2R)-cyclohexane-1,2-diamine-N,N¢]platinum and diaquodiaminocyclohexaneplatinum dimer are about 1.0 and 1.5, respectively. ]
Suitability requirements
Resolution:
NLT 2.0 between (SP-4-2)-diaqua[(1R,2R)-cyclohexane-1,2-diamine-N,N¢]platinum and diaquodiaminocyclohexaneplatinum dimer, System suitability solution
Relative standard deviation:
NMT 3.0%, Standard solution
Analysis
Samples:
Standard solution and Sample solution
Calculate the percentage of (SP-4-2)-diaqua[(1R,2R)-cyclohexane-1,2-diamine-N,N¢]platinum in the portion of Oxaliplatin for Injection taken:
Result = (rU/rS) × (CS/CU) × (Mr1/Mr2) × 100
| rU | = | = peak response of (SP-4-2)-diaqua[(1R,2R)-cyclohexane-1,2-diamine-N,N¢]platinum from the Sample solution |
| rS | = | = peak response of (SP-4-2)-diaqua[(1R,2R)-cyclohexane-1,2-diamine-N,N¢]platinum from the Standard solution |
| CS | = | = concentration of USP Oxaliplatin Related Compound B RS in the Standard solution (mg/mL) |
| CU | = | = nominal concentration of oxaliplatin in the Sample solution (mg/mL) |
| Mr1 | = | = molecular weight of (SP-4-2)-diaqua[(1R,2R)-cyclohexane-1,2-diamine-N,N¢]platinum, 345.30 |
| Mr2 | = | = molecular weight of USP Oxaliplatin Related Compound B RS, 433.28 |
Acceptance criteria:
NMT 0.5%
• Limit of Related Compound C and Unspecified Impurities
[Note—Use vigorous shaking and very brief sonication to dissolve the substance to be examined. Inject the Sample solution within 20 min of preparation. Use polypropylene HPLC autosampler vials. ]
Mobile phase:
Proceed as directed in the Assay.
Standard stock solution:
0.1 mg/mL each of USP Oxaliplatin RS and USP Oxaliplatin Related Compound C RS in water
Standard solution:
0.01 mg/mL each of USP Oxaliplatin RS and USP Oxaliplatin Related Compound C RS in water, from the Standard stock solution
System suitability stock solution:
Dissolve USP Oxaliplatin System Suitability RS in methanol, and sonicate for approximately 10 min to obtain a solution having a concentration of 0.1 mg/mL.
System suitability solution:
Transfer 10 mL each of the Standard stock solution and the System suitability stock solution into a 100-mL volumetric flask, and dilute with water to volume.
Sample solution:
Use the Sample solution from the test for Limit of Oxalic Acid.
Chromatographic system:
Proceed as directed in the Assay, except for the Injection size.
Injection size:
10 µL
System suitability
Samples:
Standard solution and System suitability solution
Suitability requirements
Resolution:
NLT 2.0 between [SP-4-2-(1R-trans)]-(1,2-cyclohexanediamine-N,N¢) dichloridoplatinum(II) and oxaliplatin, System suitability solution
Tailing factor:
NMT 2.0 for the oxaliplatin peak, System suitability solution
Relative standard deviation:
NMT 3.0% each for the oxaliplatin and oxaliplatin related compound C peaks, Standard solution
Analysis
Samples:
Standard solution and Sample solution
Calculate the percentage of oxaliplatin related compound C in the portion of Oxaliplatin for Injection taken:
Result = (rU/rS) × (CS/CU) × 100
| rU | = | = peak response of oxaliplatin related compound C from the Sample solution |
| rS | = | = peak response of oxaliplatin related compound C from the Standard solution |
| CS | = | = concentration of USP Oxaliplatin Related Compound C RS in the Standard solution (mg/mL) |
| CU | = | = nominal concentration of oxaliplatin in the Sample solution (mg/mL) |
Calculate the percentage of each unspecified impurity in the portion of Oxaliplatin for Injection taken:
Result = (rU/rS) × (CS/CU) × 100
| rU | = | = peak response of each impurity from the Sample solution |
| rS | = | = peak response of oxaliplatin from the Standard solution |
| CS | = | = concentration of USP Oxaliplatin RS in the Standard solution (mg/mL) |
| CU | = | = nominal concentration of oxaliplatin in the Sample solution (mg/mL) |
Acceptance criteria:
See Table 1.
Table 1
| Name | Relative Retention Time |
Acceptance Criteria, NMT (%) |
|---|---|---|
| Oxaliplatin related compound Ca | 0.6 | 0.3 |
| [SP-4-2-(1R-trans)]-(1,2-Cyclohexanediamine-N,N¢) dichloridoplatinum(II)b | 0.8 | — |
| Oxaliplatin | 1.0 | — |
| Any individual unspecified impurity | — | 0.2 |
| Total impuritiesc | — | 1.5 |
|
a
[1R-trans-(1,2-Cyclohexanediamine-N,N¢)]-trans-dihydroxido-[oxalato(2-)-O,O¢]platinum(IV).
b
The relative retention time of [SP-4-2-(1R-trans)]-(1,2-cyclohexanediamine-N,N¢) dichloridoplatinum(II) has been included for system suitability purposes only.
c
Includes oxalic acid, (SP-4-2)-diaqua[(1R,2R)-cyclohexane-1,2-diamine-N,N']platinum, oxaliplatin related compound C, and the total of the individual unspecified impurities.
|
||
SPECIFIC TESTS
• pH 791:
4.0–7.0 using a polymer combination electrode, determined in a solution constituted as directed in the labeling
791:
4.0–7.0 using a polymer combination electrode, determined in a solution constituted as directed in the labeling
• Particulate Matter In Injections 788:
It meets the requirements for small-volume injections.
788:
It meets the requirements for small-volume injections.
• Constituted Solution:
At the time of use, it meets the requirements under Injections 1, Constituted Solutions.
1, Constituted Solutions.
• Bacterial Endotoxins Test 85:
NMT 1.0 USP Endotoxin Unit/mg of oxaliplatin
85:
NMT 1.0 USP Endotoxin Unit/mg of oxaliplatin
• Sterility Tests 71:
Meets the requirements
71:
Meets the requirements
• Water Determination, Method 1921:
NMT 4.0%
921:
NMT 4.0%
• Other Requirements:
It meets the requirements under Injections 1.
1.
ADDITIONAL REQUIREMENTS
• Packaging and Storage:
Preserve in Containers for Sterile Solids as described under Injections 1. Store at controlled room temperature.
1. Store at controlled room temperature.
• Labeling:
Label it to indicate that it is to be diluted with a suitable parenteral vehicle before intravenous infusion.
• USP Reference Standards 11
11
USP Endotoxin RS
USP Oxaliplatin RS 
[SP-4-2-(1R-trans)]-(1,2-Cyclohexanediamine-N,N')[ethanedioato(2-)-O,O']platinum.
C8H14N2O4Pt 397.29
') + '&img=../../images/v35300/cas-61825-94-3.gif',600,500);)
[SP-4-2-(1R-trans)]-(1,2-Cyclohexanediamine-N,N')[ethanedioato(2-)-O,O']platinum.
C8H14N2O4Pt 397.29
USP Oxaliplatin Related Compound A RS
Oxalic acid dihydrate.
C2H2O4·2H2O 126.07
Oxalic acid dihydrate.
C2H2O4·2H2O 126.07
USP Oxaliplatin Related Compound B RS
[SP-4-2-(1R-trans)]-(1,2-Cyclohexanediamine-N,N¢) dinitratoplatinum(II).
C6H14N4O6Pt 433.28
[SP-4-2-(1R-trans)]-(1,2-Cyclohexanediamine-N,N¢) dinitratoplatinum(II).
C6H14N4O6Pt 433.28
USP Oxaliplatin Related Compound C RS
[1R-trans-(1,2-Cyclohexanediamine-N,N¢)]-trans-dihydroxido-[oxalato(2-)-O,O¢]platinum(IV).
C8H16N2O6Pt 431.30
[1R-trans-(1,2-Cyclohexanediamine-N,N¢)]-trans-dihydroxido-[oxalato(2-)-O,O¢]platinum(IV).
C8H16N2O6Pt 431.30
USP Oxaliplatin System Suitability RS
[SP-4-2-(1R-trans)]-(1,2-Cyclohexanediamine-N,N¢) dichloridoplatinum (II).
C6H14Cl2N2Pt 380.17
[SP-4-2-(1R-trans)]-(1,2-Cyclohexanediamine-N,N¢) dichloridoplatinum (II).
C6H14Cl2N2Pt 380.17
Auxiliary Information—
Please check for your question in the FAQs before contacting USP.
| Topic/Question | Contact | Expert Committee |
|---|---|---|
| Monograph | Feiwen Mao, M.S.
Senior Scientific Liaison 1-301-816-8320 |
(SM32010) Monographs - Small Molecules 3 |
| 85 |
Radhakrishna S Tirumalai, Ph.D.
Principal Scientific Liaison 1-301-816-8339 |
(GCM2010) General Chapters - Microbiology |
| 71 |
Radhakrishna S Tirumalai, Ph.D.
Principal Scientific Liaison 1-301-816-8339 |
(GCM2010) General Chapters - Microbiology |
| Reference Standards | RS Technical Services 1-301-816-8129 rstech@usp.org |
USP35–NF30 Page 4149
Pharmacopeial Forum: Volume No. 34(6) Page 1473