Oxaliplatin Injection
DEFINITION
Oxaliplatin Injection is a sterile solution of Oxaliplatin in Water for Injection. It contains NLT 90.0% and NMT 110.0% of the labeled amount of oxaliplatin (C8H14N2O4Pt).
IDENTIFICATION
• B.
The retention time of the major peak of the Sample solution corresponds to that of the Standard solution, as obtained in the Assay.
ASSAY
[NoteAll HPLC autosampler vials should be made of polypropylene. ]
• Procedure
Acidified water:
Adjust with phosphoric acid to a pH of 3.0.
Mobile phase:
Acetonitrile and Acidified water (1:99)
System suitability solution:
0.1 mg/mL of USP Oxaliplatin RS and 0.1 mg/mL of USP Oxaliplatin System Suitability RS in water. [NoteUSP Oxaliplatin System Suitability RS is [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:
0.1 mg/mL of oxaliplatin in water, from the combined contents of NLT three vials of Injection
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
Sample:
System suitability solution
[NoteThe relative retention times for USP Oxaliplatin System Suitability RS and oxaliplatin are 0.9 and 1.0, respectively. ]
Suitability requirements
Resolution:
NLT 2.0 between USP Oxaliplatin System Suitability RS and oxaliplatin
Tailing factor:
NMT 2.0, oxaliplatin peak
Relative standard deviation:
NMT 1.0%, oxaliplatin peak
Analysis
Samples:
Standard solution and Sample solution
Calculate the percentage of C8H14N2O4Pt in the portion of Injection taken:
Result = (rU/rS) × (CS/CU) × 100
Acceptance criteria:
90.0%110.0%
IMPURITIES
Organic Impurities
• Procedure 1: Limit of Oxalic Acid
[NoteAll HPLC autosampler vials should be made of polypropylene. ]
Solution A:
Dissolve 1.36 g of monobasic potassium phosphate in 10 mL of 10% tetrabutylammonium hydroxide, dilute with water to 1 L, and adjust with phosphoric acid to a pH of 6.0.
Mobile phase:
Acetonitrile and Solution A (1:4)
Standard solution:
35 µg/mL of USP Oxaliplatin Related Compound A RS in water. [NoteUSP Oxaliplatin Related Compound A RS is available as dihydrate oxalic acid. ]
System suitability solution:
0.1 mg/mL of succinic acid in Standard solution
Sensitivity solution:
3.5 µg/mL of USP Oxaliplatin Related Compound A RS in water, from the Standard solution
Sample solution:
Combined contents of NLT three vials of Injection
Chromatographic system
Mode:
LC
Detector:
UV 210 nm
Column:
4.6-mm × 25-cm; 5-µm packing L1
Column temperature:
40
Flow rate:
2 mL/min
Injection size:
10 µL
System suitability
Samples:
Standard solution, System suitability solution, and Sensitivity solution
[NoteThe relative retention times for succinic acid and oxalic acid are 0.8 and 1.0, respectively. ]
Suitability requirements
Resolution:
NLT 2.0 between succinic acid and oxalic acid, System suitability solution
Tailing factor:
Between 0.5 and 2.0, oxalic acid peak, System suitability solution
Signal-to-noise ratio:
NLT 10, Sensitivity solution
Relative standard deviation:
NMT 3.0%, Standard solution
Analysis
Sample:
Standard solution and Sample solution
Calculate the percentage of each impurity in the portion of Injection taken:
Result = (rU/rS) × (CS/CU) × (Mr1/Mr2) × 100
Acceptance criteria
Oxalic acid:
NMT 0.6%
• Procedure 2: Limit of (SP-4-2)-Diaqua[(1R,2R)-cyclohexane-1,2-diamine-N,N']platinum and Unspecified Impurities
[NoteAll HPLC autosampler vials should be made of polypropylene. ]
Solution A:
Dissolve 1.36 g of monobasic potassium phosphate and 0.55 g of sodium heptanesulfonate in 1 L of water. Adjust with phosphoric acid to a pH of 3.0.
Solution B:
Methanol and Solution A (19:81)
Solution C:
Methanol and Solution A (50.5:49.5)
Mobile phase:
See the gradient table below.
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. Transfer 5 mL of this solution into a 50-mL volumetric flask, and dilute with water to volume. [NoteThe preparation of the System suitability solution forms (SP-4-2)-diaqua[(1R,2R)-cyclohexane-1,2-diamine-N,N']platinum and diaquodiaminocyclohexaneplatinum dimer. ]
Standard stock solution:
Transfer a weighed quantity of USP Oxaliplatin Related Compound B RS into a suitable volumetric flask, add a volume of methanol equivalent to about 25% of the final volume, and sonicate for approximately 2 min to disperse the solids. Add a volume of 0.01 M nitric acid equivalent to about 65% of the final volume, and sonicate for approximately 30 min to dissolve. Allow to cool if necessary, and dilute with 0.01 M nitric acid to volume to obtain a solution of concentration of 0.125 mg/mL.
Standard solution:
31.25 µg/mL of USP Oxaliplatin Related Compound B RS in 0.01 M nitric acid, from the Standard stock solution. [NoteUSP Oxaliplatin Related Compound B RS is converted to (SP-4-2)-diaqua[(1R,2R)-cyclohexane-1,2-diamine-N,N']platinum in the Standard solution preparation. ]
Sample solution:
Combined contents of NLT three vials of Injection
Chromatographic system
Mode:
LC
Detector:
UV 210 nm
Column:
4.6-mm × 7.5-cm; 3-µm packing L1
Column temperature:
10
Flow rate:
1 mL/min
Injection size:
20 µL
System suitability
Samples:
System suitability solution and Standard solution
Suitability requirements
Resolution:
NLT 8.0 between the peaks of (SP-4-2)-diaqua[(1R,2R)-cyclohexane-1,2-diamine-N,N']platinum and diaquodiaminocyclohexaneplatinum dimer, System suitability solution.
Tailing factor:
NMT 2.0, (SP-4-2)-diaqua[(1R,2R)-cyclohexane-1,2-diamine-N,N']platinum peak, System suitability solution
Relative standard deviation:
NMT 3.0%, Standard solution
Analysis
Samples:
Standard solution and Sample solution
Calculate the percentage of each impurity in the portion of Injection taken:
Result = (rU/rS) × (CS/CU) × (Mr1/Mr2) × (1/F) × 100
Acceptance criteria
Individual impurities:
See Impurity Table 1.
Total impurities:
NMT 2.45%, from Limit of oxalic acid and Limit of (SP-4-2)-Diaqua[(1R,2R)-cyclohexane-1,2-diamine-N,N']platinum and Unspecified Impurities
Impurity Table 1
SPECIFIC TESTS
• Bacterial Endotoxins Test 85:
It contains NMT 1.0 USP Endotoxin Units/mg of oxaliplatin.
• Sterility Tests 71:
It meets the requirements when tested as directed for Membrane Filtration under Test for Sterility of the Product to Be Examined.
• pH 791:
Between 4.0 and 7.0 using a polymer combination electrode
• Particulate Matter in Injections 788:
It meets the requirements for small-volume injections.
• Other Requirements:
It meets the requirements under Injections 1.
ADDITIONAL REQUIREMENTS
• Packaging and Storage:
Preserve in single-dose or multiple-dose containers, preferably of Type I glass, protected from light. Store at controlled room temperature. Do not freeze.
• Labeling:
Label it to indicate that it is to be diluted with a 5% dextrose solution. Oxaliplatin Injection must not be diluted in sodium chloride solutions or in chloride-containing solutions.
• USP Reference Standards 11
USP Endotoxin RS
USP Oxaliplatin Related Compound A RS
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
USP Oxaliplatin System Suitability RS
[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.
USP35NF30 Page 4147
Pharmacopeial Forum: Volume No. 35(2) Page 284
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