Cycloserine
;)
3-Isoxazolidinone,4-amino-,(R)-.
(+)-4-Amino-3-isoxazolidinone [68-41-7].
»Cycloserine has a potency of not less than 900µg of C3H6N2O2per mg.
Packaging and storage—
Preserve in tight containers.
Identification—
Dissolve about 1mg in 10mLof 0.1Nsodium hydroxide.To 1mLof the resulting solution add 3mLof 1Nacetic acid and 1mLof a mixture,prepared 1hour before use,of equal parts of sodium nitroprusside solution (1in 25)and 4Nsodium hydroxide:a blue color gradually develops.
Condensation products—
Its absorptivity (see Spectrophotometry and Light-Scattering á851ñ)at 285nm,determined in a 0.1Nsodium hydroxide solution containing 0.40mg per mLis not more than 0.80.
Specific rotation á781Sñ:
between 108
and 114.
and 114.
Test solution:
50mg per mL,in 2Nsodium hydroxide.
Crystallinity á695ñ:
meets the requirements.
pHá791ñ:
between 5.5and 6.5,in a solution (1in 10).
Loss on drying á731ñ—
Dry about 100mg in a capillary-stoppered bottle in vacuum at 60for 3hours:it loses not more than 1.0%of its weight.
for 3hours:it loses not more than 1.0%of its weight.
Residue on ignition á281ñ:
not more than 0.5%,the charred residue being moistened with 2mLof nitric acid and 5drops of sulfuric acid.
Assay—
pH6.8Phosphate buffer—
Prepare as directed in Buffer Solutionsunder Solutionsin the section Reagents,Indicators,and Solutions.
Mobile phase—
Dissolve 0.5g of sodium 1-decanesulfonate in 800mLof water,add 50mLof acetonitrile and 5mLof glacial acetic acid,and mix.Adjust with 1Nsodium hydroxide to a pHof 4.4.Filter,and degas.Make adjustments if necessary (see System Suitabilityunder Chromatography á621ñ).
Standard preparation—
Quantitatively dissolve an accurately weighed quantity of USP Cycloserine RSin pH6.8Phosphate bufferto obtain a solution having a known concentration of about 0.4mg per mL.
Assay preparation—
Transfer about 20mg of Cycloserine,accurately weighed,to a 50-mLvolumetric flask,dissolve in and dilute with pH6.8Phosphate bufferto volume,and mix.
Chromatographic system (see Chromatography á621ñ)—
The liquid chromatograph is equipped with a 219-nm detector and a 4.6-mm ×25-cm column that contains 5-µm packing L1.The flow rate is about 1mLper minute.The column temperature is maintained at about 30.Chromatograph the Standard preparation,and record the peak responses as directed for Procedure:the tailing factor is not more than 1.8;and the relative standard deviation for replicate injections is not more than 2.0%.
.Chromatograph the Standard preparation,and record the peak responses as directed for Procedure:the tailing factor is not more than 1.8;and the relative standard deviation for replicate injections is not more than 2.0%.
Procedure—
Separately inject equal volumes (about 10µL)of the Standard preparationand the Assay preparationinto the chromatograph,record the chromatograms,and measure the peak responses for cycloserine.Calculate the quantity,in µg,of C3H6N2O2in each mg of Cycloserine taken by the formula:
50,000(C/W)(rU/rS),
in which Cis the concentration,in mg per mL,of USP Cycloserine RSin the Standard preparation;Wis the quantity,in mg,of Cycloserine taken to prepare the Assay preparation;and rUand rSare the peak responses for cycloserine obtained from the Assay preparationand the Standard preparation,respectively.
Auxiliary Information—
Staff Liaison:William W.Wright,Ph.D.,Scientific Fellow
Expert Committee:(PA7)Pharmaceutical Analysis 7
USP28–NF23Page 560
Pharmacopeial Forum:Volume No.27(5)Page 2998
Phone Number:1-301-816-8335