Ropivacaine Hydrochloride Injection
» Ropivacaine Hydrochloride Injection is a sterile solution of Ropivacaine Hydrochloride in Water for Injection. It contains not less than 90.0 percent and not more than 110.0 percent of the labeled amount of ropivacaine hydrochloride (C17H26N2O·HCl).
Packaging and storage— Preserve in single-dose or multiple-dose containers, preferably of Type 1 glass or of suitable plastic.
USP Reference standards 11
USP Endotoxin RS
USP Ropivacaine Hydrochloride RS Click to View Structure
USP Ropivacaine Related Compound A RS
2,6-Dimethylaniline hydrochloride.
    C8H12ClN    157.64 [CAS-21436-98-6].
USP Ropivacaine Related Compound B RS
(R)-ropivacaine hydrochloride monohydrate; (R)-(–)-1-propylpiperidene-2-carboxylic acid (2,6-dimethylphenyl)-amide hydrochloride monohydrate.
    C17H26N2O    328.89
Identification—
A: The retention time of the major peak in the chromatogram of the Assay preparation corresponds to that in the chromatogram of the Standard preparation, as obtained in the Assay.
B: The retention time of the major peak in the chromatogram of the Test solution corresponds to that in the chromatogram of the System suitability solution, as obtained in the test for Enantiomeric purity.
Bacterial endotoxins 85 It contains not more than 60 USP Endotoxin Units per g of ropivacaine hydrochloride.
Particulate matter 788: meets the requirements for injections.
Sterility 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 6.0.
Limit of 2,6-dimethylaniline (ropivacaine related compound A, base)—
pH 8.0 Buffer solution and Mobile phase— Prepare as directed in the Assay.
Standard solution— Prepare as directed for Standard preparation in the Assay.
Test solution— Dilute accurately the Injection with Mobile phase to obtain a concentration of 2.0 mg per mL.
Chromatographic system (see Chromatography 621) The liquid chromatograph is equipped with a 240-nm detector and a 3.9-mm × 15-cm column that contains 5-µm packing L1. The flow rate is about 1.5 mL per minute. Chromatograph the Standard solution, and record the peak responses as directed for Procedure: the resolution, R, between ropivacaine related compound A and ropivacaine is not less than 5; and the signal-to-noise ratio for ropivacaine related compound A is not less than 10.
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 peak responses. The peak response of ropivacaine related compound A obtained from the Test solution is not greater than the corresponding response obtained from the Standard solution (not more than 0.01% of ropivacaine related compound A base is found).
Enantiomeric purity—
pH 7.2 Buffer solution— Transfer 7.5 mL of 1 M monobasic sodium phosphate solution and 28.5 mL of 0.5 M dibasic sodium phosphate dihydrate solution into a 1-L volumetric flask, and dilute with water to volume. Adjust the resulting solution to a pH of 7.2, if necessary.
Mobile phase— Transfer 35 mL of isopropyl alcohol into a 500-mL volumetric flask, dilute with pH 7.2 Buffer solution to volume, mix, and degas. Make adjustments if necessary (see System Suitability under Chromatography 621).
System suitability solution— Dissolve suitable quantities of USP Ropivacaine Hydrochloride RS and USP Ropivacaine Related Compound B RS in water, and dilute quantitatively, and stepwise, with water to obtain a solution containing about 75 µg per mL and 0.75 µg per mL, respectively.
Test solution— Dilute the Injection with Mobile phase to a concentration of about 75 µg per mL.
Chromatographic system (see Chromatography 621) The liquid chromatograph is equipped with a 220-nm detector and a 4-mm × 10-cm column that contains packing L41. The flow rate is about 1 mL per minute. Chromatograph the System suitability solution, and record the peak responses as directed for Procedure: the resolution, R, between ropivacaine related compound B (R enantiomer) and ropivacaine (S enantiomer) is not less than 1.5. [note—For the purpose of identification, the relative retention times are about 0.75 for ropivacaine related compound B and 1.0 for ropivacaine. ]
Procedure— Inject about 20 µL of the Test solution into the chromatograph, record the chromatogram, and measure the peak responses. Calculate the percentage of ropivacaine related compound B (R enantiomer) in the portion of Injection taken by the formula:
100(ri / rs)
in which ri is the peak response of ropivacaine related compound B (R enantiomer); and rs is the sum of the peak responses of ropivacaine (S enantiomer) and ropivacaine related compound B (R enantiomer) obtained from the Test solution: not more than 2.0% of ropivacaine related compound B (R enantiomer) is found.
Other requirements— It meets the requirements under Injections 1.
Assay—
pH 8.0 Buffer solution— Transfer 1.3 mL of 1 M monobasic sodium phosphate solution and 32.5 mL of 0.5 M dibasic sodium phosphate dihydrate solution to a 1-L volumetric flask. Dilute with water to volume, and mix. Adjust the resulting solution to a pH of 8.0, if necessary.
Mobile phase— Prepare a filtered and degassed mixture of acetonitrile and pH 8.0 Buffer solution (60:40). Make adjustments if necessary (see System Suitability under Chromatography 621).
Standard preparation— Dissolve accurately weighed quantities of USP Ropivacaine Hydrochloride RS and USP Ropivacaine Related Compound A RS in Mobile phase, and dilute quantitatively, and stepwise, with Mobile phase to obtain a solution having known concentrations of about 0.25 mg per mL of USP Ropivacaine Hydrochloride RS and about 0.26 µg per mL of USP Ropivacaine Related Compound A RS.
Assay preparation— Dilute accurately the Injection with Mobile phase to obtain a concentration of about 0.25 mg per mL.
Chromatographic system (see Chromatography 621)— The liquid chromatograph is equipped with a 240-nm detector and a 3.9-mm × 15-cm column that contains 5- or 10-µm packing L1. The flow rate is about 1.2 mL per minute. Chromatograph the Standard preparation, and record the peak responses as directed for Procedure: the relative standard deviation for replicate injections, calculated for the ropivacaine peak, is not more than 1.0%; and the resolution, R, between ropivacaine related compound A and ropivacaine is not less than 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 quantity, in mg, of ropivacaine hydrochloride (C17H26N2O·HCl) in each mL of Injection taken by the formula:
CD(rU / rS)
in which C is the concentration, in mg per mL, of USP Ropivacaine Hydrochloride RS in the Standard preparation; D is the dilution factor, in mL, for the Assay preparation; 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
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
USP35–NF30 Page 4591
Pharmacopeial Forum: Volume No. 32(2) Page 374