(van'' koe mye' sin hye'' droe klor' ide).
(Sa)-(3S,6R,7R,22R,23S,26S,36R,38aR)-44-[[2-O-(3-Amino-2,3,6-trideoxy-3-C-methyl--l-lyxo-hexopyranosyl)--d-glucopyranosyl]oxy]-3-(carbamoylmethyl)-10,19-dichloro-2,3,4,5,6,7,23,24,25,26,36,37,38,38a-tetradecahydro-7,22,28,30,32-pentahydroxy-6-[(2R)-4-methyl-2-(methylamino)]valeramido]-2,5,24,38,39-pentaoxo-22H-8,11:18,21-dietheno-23,36-(iminomethano)-13,16:31,35-dimetheno-1H,16H-[1,6,9]oxadiazacyclohexadecino[4,5-m][10,2,16]benzoxadiazacyclotetracosine-26-carboxylic acid, monohydrochloride;
[3S-[3R*,6S*(S*),7S*,22S*,23R*,26R*,36S*,38aS*]]-3-(2-Amino-2-oxoethyl)-44-[[2-O-(3-amino-2,3,6-trideoxy-3-C-methyl--l-lyxo-hexopyranosyl)--d-glucopyranosyl]oxy]-10,19-dichloro-2,3,4,5,6,7,23,24,25,26,36,37,38,38a-tetradecahydro-7,22,28,30,32-pentahydroxy-6-[[4-methyl-2-(methylamino)-1-oxopentyl]amino]-2,5,24,38,39-pentaoxo-22H-8,11:18,21-dietheno-23,36-(iminomethano)-13,16:31,35-dimetheno-1H,16H-[1,6,9]oxadiazacyclohexadecino[4,5-m][10,2,16]-benzoxadiazacyclotetracosine-26-carboxylic acid, monohydrochloride [1404-93-9].
Vancomycin Hydrochloride is the hydrochloride salt of a kind of vancomycin, a substance produced by the growth of Streptomyces orientalis (Fam. Streptomycetaceae), or a mixture of two or more such salts. It has a potency equivalent to NLT 900 µg/mg of vancomycin, calculated on the anhydrous basis.
• Procedure: Proceed with Vancomycin Hydrochloride as directed under AntibioticsMicrobial Assays 81.
Acceptance criteria: NLT 900 µg/mg on the anhydrous basis
• Heavy Metals, Method II 231: NMT 30 ppm
• Procedure: Limit of Monodechlorovancomycin
[NoteThe System suitability solution, Standard solution, and Sample solution should be refrigerated immediately after preparation and during analysis. The solutions are stable for 4 days when refrigerated. ]
Mobile phase: Dissolve 2.2 g of 1-heptanesulfonic acid sodium salt in about 500 mL of water, add 125 mL of acetonitrile and 10 mL of acetic acid, and dilute with water to 1 L.
Rinse solution: 10% acetonitrile in water. [NoteUse to rinse needle and column. ]
System suitability solution: Equivalent to 1 mg/mL of vancomycin B from USP Vancomycin B with Monodechlorovancomycin RS in water
Standard solution: Equivalent to 50 µg/mL of vancomycin B, from System suitability solution
Sample solution: 1 mg/mL of Vancomycin Hydrochloride in water
Detector: UV 280 nm
Column: 4.6 mm × 25 cm; packing L1
Column temperature: 60
Autosampler temperature: 5
Flow rate: 1.5 mL/min
Injection volume: 50 µL
[NoteThis procedure is sensitive to temperature changes. Sufficient tubing should be placed in the column oven to ensure that the samples have reached 60 before separation. ]
Samples: System suitability solution, Standard solution, Sample solution, and Blank
[NoteBlank and Standard solution run times are about 90 min. System suitability solution and Sample solution run times are about 120 min. ]
[NoteThe relative retention times for vancomycin B and monodechlorovancomycin are 1.0 and 1.1, respectively. ]
Selectivity: The chromatogram for the Blank does not contain peaks that interfere with vancomycin B or monodechlorovancomycin.
Retention times: ±3.0% between monodechlorovancomycin in the Sample solution and the mean of the monodechlorovancomycin peaks in the Standard solution
Resolution: NLT 1.5 between vancomycin B and monodechlorovancomycin, System suitability solution
Relative standard deviation: NMT 2.0%, Standard solution
Samples: Standard solution and Sample solution
Calculate the percentage of monodechlorovancomycin in the portion of Vancomycin Hydrochloride taken:
Result = (rU/rS) × (CS/CU) × P × 100
Acceptance criteria: NMT 4.7% of monodechlorovancomycin is found.
• Sterility Tests 71: Where the label states that Vancomycin Hydrochloride is sterile, it meets the requirements when tested as directed for Test for Sterility of the Product to Be Examined, Membrane Filtration, except to dissolve the specimen in water, instead of in Fluid A.
• Bacterial Endotoxins Test 85: Where the label states that Vancomycin Hydrochloride is sterile or must be subjected to further processing during the preparation of injectable dosage forms, it contains NMT 0.33 USP Endotoxin Unit/mg of vancomycin.
• pH 791: 2.54.5, 50 mg/mL in water
• Water Determination, Method I 921: NMT 5.0%
• Composition of Vancomycin
Solution A: Triethylamine and water (1:500). Adjust with phosphoric acid to a pH of 3.2.
Solution B: Acetonitrile, tetrahydrofuran, and Solution A (7:1:92)
Solution C: Acetonitrile, tetrahydrofuran, and Solution A (29:1:70)
Mobile phase: See the gradient table below. [NoteMake adjustments, if necessary, changing the acetonitrile proportion in Solution B to obtain a retention time of 7.510.5 min for the main vancomycin peak. ]
System suitability solution: 0.5 mg/mL of USP Vancomycin Hydrochloride RS in water. Heat at 65 for 48 h, and allow to cool.
Sample solution 1: 10 mg/mL of Vancomycin Hydrochloride in Solution B
Sample solution 2: 0.4 mg/mL of Vancomycin Hydrochloride, from Sample solution 1 in Solution B
Detector: UV 280 nm
Column: 4.6-mm × 25-cm; 5-µm packing L1
Flow rate: 2 mL/min
Injection size: 20 µL
Sample: System suitability solution
[NoteThe elution order is compound 1, vancomycin B, and compound 2. Compound 2 elutes 36 min after the start of the period when the percentage of Solution C increases from 0%100%. ]
Resolution: NLT 3.0 between compound 1 and vancomycin B
Column efficiency: NLT 1500 theoretical plates, calculated from the vancomycin B peak
Samples: Sample solution 1 and Sample solution 2
[NoteWhere baseline separation is not achieved, peak areas are defined by vertical lines extended from the valleys between the peaks to the baseline. The main component peak may include a fronting shoulder, which is attributed to monodechlorovancomycin. This shoulder should not be integrated separately. ]
[NoteCorrect any peak observed in the chromatograms obtained from Sample solution 1 and Sample solution 2 by subtracting the area response of any peak observed in the chromatogram of Solution B at the corresponding retention time. ]
Measure the area responses for all of the peaks. Calculate the percentage of vancomycin B in the portion of Vancomycin Hydrochloride taken:
Result = [(D × rB)/((D × rB) + rA)] × 100
Calculate the percentage of each other peak in the portion of Vancomycin Hydrochloride taken:
Result = [(rI/(D × rB) + rA)] × 100
Acceptance criteria: NLT 85.0% of vancomycin B; NMT 5.0% of any peak other than the main peak
• Packaging and Storage: Preserve in tight containers.
• Labeling: Where it is intended for use in preparing injectable dosage forms, the label states that it is sterile or must be subjected to further processing during the preparation of injectable dosage forms.
• USP Reference Standards 11
USP Endotoxin RS
USP Vancomycin B with Monodechlorovancomycin RS
Auxiliary Information Please check for your question in the FAQs before contacting USP.
USP35NF30 Page 5001Pharmacopeial Forum: Volume No. 35(4) Page 879