Pentobarbital Sodium
C11H17N2NaO3 248.25

2,4,6(1H,3H,5H)-Pyrimidinetrione,5-ethyl-5-(1-methylbutyl)-,monosodium salt.
Sodium 5-ethyl-5-(1-methylbutyl)barbiturate [57-33-0].
Change to read:
»Pentobarbital Sodium contains not less than 98.0USP28percent and not more than 102.0USP28percent of C11H17N2NaO3,calculated on the dried basis.
Packaging and storage— Preserve in tight containers.
Completeness of solution— Mix 1.0g with 10mLof carbon dioxide-free water:after 1minute,the solution is clear and free from undissolved solid.
Change to read:
Identification—
A:
Ultraviolet Absorption á197Uñ—
Solution: 10µg per mL.
Medium: dilute ammonium hydroxide (1in 200).USP28
B: 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.
C:USP28 Ignite about 200mg:the residue effervesces with acids,and meets the requirements of the tests for Sodium á191ñ.
pHá791ñ: between 9.8and 11.0,in the solution prepared in the test for Completeness of solution.
Loss on drying á731ñ— Dry it at 105for 6hours:it loses not more than 3.5%of its weight.
Add the following:
Related compounds—
Mobile phase— Prepare as described in the Assay.
Standard solution— Dissolve an accurately weighed quantity of USP Pentobarbital RSin Mobile phase,and dilute quantitatively,and stepwise if necessary,with Mobile phase to obtain a solution having a known concentration of about 0.001mg per mL.
Test solution— Transfer about 110mg of Pentobarbital Sodium,accurately weighed,to a 100-mLvolumetric flask,add about 80mLof Mobile phase,and sonicate until dissolved.Dilute with Mobile phaseto volume,and mix.
Chromatographic system (seeChromatography á621ñ)— The liquid chromatograph is equipped with a 214-nm detector and a 4.6-mm ×25-cm column that contains 5-µm packing L1.The flow rate is about 1.0mLper minute.Chromatograph the Standard solution,and record the peak responses as directed for Procedure:the capacity factor,k¢,is not less than 2.5;the column efficiency is not less than 15,000theoretical plates;the tailing factor is not more than 1.5;and the relative standard deviation for replicate injections is not more than 15.0%.
Procedure— Separately inject equal volumes (about 10µL)of the Standard solution and Test solutioninto the chromatograph,record the chromatograms,and measure the areas for the major peaks.Calculate the percentage of any impurity in the portion of Pentobarbital Sodium taken by the formula:
(248.25/226.27)(10,000/F)(C/W)(ri/rS),
in which 248.25and 226.27are the molecular weights of pentobarbital sodium and pentobarbital,respectively;Cis the concentration,in mg per mL,of USP Pentobarbital RSin the Standard solution;Fis the relative response factor of the impurity according to the table below;Wis the weight,in mg,of Pentobarbital Sodium,on the dried basis,used to prepare the Test solution;riis the peak area for any impurity in the Test solution;and rSis the peak area for Pentobarbital in the Standard solution:the impurities meet the requirements given in the table below:
Compound
Name		 Relative
Retention
Time		 Relative
Response
Factor		 Limit (%)
6-Imino-5-ethyl-
5-(1-methyl-
butyl)barbituric
acid		 about 0.39 1.5 0.2
5-Ethyl-5-(1-ethyl-propyl)barbituric acid* about 0.93 1.0 0.1
Pentobarbital 1.0 — —
5-Ethyl-5-(1,3-
dimethylbutyl)
barbituric acid		 about 1.5 0.9 0.3
Unknown
impurities		 — 1.0 0.1
Total — — 0.5
*  Where the material is labeled as intended solely for veterinary use,the limit of 5-ethyl-5-(1-ethylpropyl)barbituric acid is 3.0%.
USP28
Organic volatile impurities,Method Iá467ñ: meets the requirements.
Delete the following:
Isomer content— Dissolve 300±5mg in 5.0mLof water,and dissolve 300±5mg of p-nitrobenzyl bromide in 10.0mLof alcohol.Mix the two solutions,reflux for 30minutes,cool to 25,and filter by suction.Wash the collected solid with four 5-mLportions of water,transfer as completely as practicable to a small flask,add 25.0mLof alcohol,and reflux for 10minutes:the solid dissolves completely.Cool the solution to 25,and filter by suction:the collected solid,after being dried at 105for 30minutes,melts completely between 136and 146,when determined by the procedure for Class Ia(see Melting Range or Temperature á741ñ).USP28
Change to read:
Assay—
NOTE—Use the value for Loss on drying obtained at the same time as the preparation of the Test solution in the test for Related compounds and the Assay preparation in the Assay.
Mobile phase,Standard preparation,andChromatographic system— Proceed as described in the Assayunder Pentobarbital.
Assay preparation— Transfer about 110mg of Pentobarbital Sodium,accurately weighed,to a 100-mLvolumetric flask,add about 80mLof Mobile phase,and sonicate until dissolved.Dilute with Mobile phaseto volume,and mix.Transfer 10.0mLof this solution to a 100-mLvolumetric flask.Dilute with Mobile phaseto volume,and mix.
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 the major peak.Calculate the quantity,in mg,of C11H17N2NaO3in the portion of Pentobarbital Sodium taken by the formula:
(248.25/226.27)1000C(rU/rS),
in which 248.25and 226.27are the molecular weights of pentobarbital sodium and pentobarbital,respectively;Cis the concentration,in mg per mL,of USP Pentobarbital RSin the Standard preparation;and rUand rSare the peak areas obtained from the Assay preparationand the Standard preparation,respectively.USP28
Auxiliary Information— Staff Liaison:Ravi Ravichandran,Ph.D.,Senior Scientist
Expert Committee:(PA3)Pharmaceutical Analysis 3
USP28–NF23Page 1509
Pharmacopeial Forum:Volume No.30(1)Page 157
Phone Number:1-301-816-8330
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