Methyldopa Oral Suspension
»Methyldopa Oral Suspension is an aqueous suspension of Methyldopa.It contains one or more suitable flavors,wetting agents,and preservatives,and it may contain Sucrose.It contains not less than 90.0percent and not more than 110.0percent of the labeled amount of C10H13NO4.
Packaging and storage— Preserve in tight,light-resistant containers,and store at a temperature not exceeding 26.
Identification— Apply 10-µLportions of the Assay preparationand the Standard preparationprepared as directed in the Assayto a suitable thin-layer chromatographic plate (see Chromatography á621ñ)coated with a 0.25-mm layer of chromatographic silica gel mixture.Allow to dry,develop the chromatogram in a solvent system consisting of equal volumes of acetone,butyl alcohol,glacial acetic acid,toluene,and water until the solvent front has moved about three-fourths of the length of the plate.Remove the plate from the developing chamber,mark the solvent front,and allow the solvent to evaporate.Locate the spots by staining the plate with iodine vapor for about 50minutes,then view the plate under short-wavelength UVlight:the RFvalue of the principal spot obtained from the Assay preparationcorresponds to that obtained from the Standard preparation.
Uniformity of dosage units á905ñ—
FOR ORAL SUSPENSION PACKAGED IN SINGLE-UNIT CONTAINERS: meets the requirements.
Deliverable volume á698ñ—
FOR ORAL SUSPENSION PACKAGED IN MULTIPLE-UNIT CONTAINERS: meets the requirements.
pHá791ñ: between 3.0and 5.0;between 3.2and 3.8if sucrose is present.
Limit of methyldopa-glucose reaction product [TO BE DETERMINED IF SUCROSE IS PRESENT]—
Mobile phase— Prepare as directed in the Assay.
Solution A— Dissolve a suitable,accurately weighed quantity of USP Methyldopa-glucose Reaction Product RSin 0.1Nsulfuric acid to obtain a solution having a known concentration of about 0.45mg per mL.
Standard solution— Transfer about 25mg of USP Methyldopa RS,accurately weighed,to a 25-mLvolumetric flask,add 1.0mLof Solution A,dilute with 0.1Nsulfuric acid to volume,and mix.The Standard solutionhas a known concentration of about 18µg of USP Methyldopa-glucose Reaction Product RSper mL.
Test solution— Prepare as directed for Assay preparationin the Assay.
Chromatographic system— Use the system described under Chromatographic systemin the Assay.The relative retention times for methyldopa and methyldopa-glucose reaction product are about 1.0and 0.8,respectively.Chromatograph three replicate injections of the Standard solution:the resolution factor,R,between methyldopa and methyldopa-glucose reaction product is not less than 2.0.The relative standard deviations for three replicate injections of the Standard solutionare not more than 2.0%and 3.0%for methyldopa and methyldopa-glucose reaction product,respectively.
Procedure— Proceed as directed for Procedurein the Assay.Calculate the quantity,in µg,of methyldopa equivalent to the methyldopa-glucose reaction product in each mLof the Oral Suspension taken by the formula:
(211.22/373.35)(250)(CD/W)(rU/rS),
in which 211.22and 373.35are the molecular weights of anhydrous methyldopa and methyldopa-glucose reaction product,respectively;Cis the concentration,in µg per mL,of USP Methyldopa-glucose Reaction Product RSin the Standard solution;rUand rSare the peak responses of the methyldopa-glucose reaction product obtained from the Test solutionand the Standard solution,respectively;and the other terms are as defined therein.The limit is 10.0%,based on the methyldopa content of the Oral Suspension as determined in the Assay.
Assay—
Mobile phase— To 6.8g of monobasic potassium phosphate add 750mLof water,and stir until solution is complete.Adjust with 1Mphosphoric acid to a pHof 3.5,dilute with water to 1000mL,mix,and pass through a filter having a 10-µm or finer porosity.
Standard preparation— Dissolve an accurately weighed quantity of USP Methyldopa RSin 0.1Nsulfuric acid to obtain a solution having a known concentration of about 1mg of anhydrous methyldopa per mL.
Assay preparation— Transfer an accurately measured volume of Oral Suspension,freshly mixed,equivalent to about 250mg of methyldopa,to a 250-mLvolumetric flask,dilute with 0.1Nsulfuric acid to volume,and mix to dissolve the methyldopa.Pass the solution through a 0.45-µm membrane filter before using.
Chromatographic system(see Chromatography á621ñ)— The liquid chromatograph is equipped with a 280-mm detector and a 3.9-mm ×30-cm column that contains packing L1.The flow rate is about 1mLper minute.Chromatograph three replicate injections of the Standard preparation,and record the peak responses as directed for Procedure:the relative standard deviation is not more than 2.0%.
Procedure— Separately inject equal volumes (about 50µL)of the Standard preparationand the Assay preparationinto the chromatograph by means of a suitable microsyringe or sampling valve,record the chromatograms,and measure the responses for the major peaks.Calculate the quantity,in mg,of C10H13NO4in each mLof the Oral Suspension taken by the formula:
250(C/V)(rU/rS),
in which Cis the concentration,in mg per mL,of USP Methyldopa RSin the Standard preparation;Vis the volume,in mL,of Oral Suspension taken;and rUand rSare the peak responses obtained from the Assay preparationand the Standard preparation,respectively.
Auxiliary Information— Staff Liaison:Andrzej Wilk,Ph.D.,Senior Scientific Associate
Expert Committee:(PA5)Pharmaceutical Analysis 5
USP28–NF23Page 1259
Pharmacopeial Forum:Volume No.29(6)Page 1931
Phone Number:1-301-816-8305