Divalproex Sodium
(dye val' proe ex soe' dee um).
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(C16H31NaO4)n 310.41
Pentanoic acid, 2-propyl-, sodium salt (2:1);    
Sodium hydrogen bis(2-propylvalerate) oligomer.    
Divalproex Sodium contains NLT 98.0% and NMT 102.0% of available valproic acid (C8H16O2).
•  B. Identification Tests—General, Sodium 191
Sample:  100 mg
Analysis:  Ignite the Sample.
Acceptance criteria:  Meets the requirements
•  Procedure
Solution A:  3.5 g of monobasic sodium phosphate monohydrate in 900 mL of water. Adjust with phosphoric acid to a pH of 3.5. Dilute with water to 1 L.
Mobile phase:  Acetonitrile and Solution A (1:1)
Impurity stock solution:  0.5 mg/mL of USP Valproic Acid Related Compound A RS in acetonitrile
Standard stock solution:  5.0 mg/mL of USP Valproic Acid RS in Mobile phase
System suitability solution:  0.5 mg/mL of valproic acid from the Standard stock solution, and 5 µg/mL of valproic acid related compound A from the Impurity stock solution, in Mobile phase
Standard solution:  0.5 mg/mL of USP Valproic Acid RS from the Standard stock solution in Mobile phase
Sample solution:  0.5 mg/mL of Divalproex Sodium in Mobile phase
Chromatographic system 
Mode:  LC
Detector:  UV 215 nm
Column:  4.6-mm × 15-cm; 5-µm packing L7
Flow rate:  1 mL/min
Injection size:  20 µL
System suitability 
Sample:  System suitability solution
[Note—The relative retention times for valproic acid related compound A and valproic acid are 0.69 and 1.0, respectively. ]
Suitability requirements 
Resolution:  NLT 5.0 between valproic acid related compound A and valproic acid
Tailing factor:  NMT 1.5 for the valproic acid peak
Relative standard deviation:  NMT 2.0%
Samples:  Standard solution and Sample solution
Calculate the percentage of available valproic acid (C8H16O2) in the portion of Divalproex Sodium taken:
Result = (rU/rS) × (CS/CU) × (Mr1/Mr2) × (1/F) × 100
rU== peak area from the Sample solution
rS== peak area from the Standard solution
CS== concentration of USP Valproic Acid RS in the Standard solution (mg/mL)
CU== concentration of the Sample solution (mg/mL)
Mr1== molecular weight for divalproex sodium repeating unit, 310.41
Mr2== molecular weight for valproic acid, 144.21
F== number of moles of valproic acid per mole of divalproex sodium repeating unit, 2
Acceptance criteria:  98.0%–102.0%
Inorganic Impurities 
•  Heavy Metals, Method II 231: NMT 20 ppm
•  Packaging and Storage: Preserve in tight containers. Store at room temperature.
•  USP Reference Standards 11
USP Divalproex Sodium RS Click to View Structure
Sodium hydrogen bis(2-propylvalerate), oligomer; pentanoic acid, 2-propyl-, sodium salt (2:1).
    (C16H31NaO4)n        310.41
USP Valproic Acid RS Click to View Structure
USP Valproic Acid Related Compound A RS Click to View Structure
Auxiliary Information— Please check for your question in the FAQs before contacting USP.
Topic/Question Contact Expert Committee
Monograph Ravi Ravichandran, Ph.D.
Principal Scientific Liaison
(SM42010) Monographs - Small Molecules 4
Reference Standards RS Technical Services
USP35–NF30 Page 2945
Pharmacopeial Forum: Volume No. 36(5) Page 1178