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Currently Official as of: 16-Sep-2019
Official as of 1-Jan-2018
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Valproic Acid

C8H16O2 144.21
Pentanoic acid, 2-propyl-;
Propylvaleric acid [99-66-1]; UNII: 614OI1Z5WI.

DEFINIT ION
Valproic Acid contains NLT 98.0% and NMT 102.0% of valproic acid (C8H16O2), calculated on the anhydrous basis.

IDENT IFIC AT ION

• A. I A 〈197F〉
• B. The retention time of the major peak of the Sample solution corresponds to that of the Standard solution, as obtained in the Assay.

ASSAY
•P
Buffer: 3.5 g/L of monobasic sodium phosphate in water. Adjust with phosphoric acid to a pH of 3.5.
Mo bile phas e: Acetonitrile and Buffer (45:55)
Diluent : Acetonitrile and water (45:55)
Sys t em s uit abilit y s o lut io n: 50 µg/mL of USP Valproic Acid Related Compound B RS and 0.5 mg/mL of USP Valproic Acid RS in Diluent
St andard s o lut io n: 0.5 mg/mL of USP Valproic Acid RS in Diluent
Sample s o lut io n: 0.5 mg/mL of Valproic Acid in Diluent
C hro mat o graphic s ys t em
(See Chromatography 〈621〉, System Suitability.)
Mo de: LC
Det ect o r: UV 215 nm
C o lumn: 4.6-mm × 15.0-cm; 5-µm packing L7
Flo w rat e: 1 mL/min
Inject io n vo lume: 20 µL
Sys t em s uit abilit y
Samples : System suitability solution and Standard solution
Suit abilit y requirement s
Res o lut io n: NLT 2.0 between valproic acid related compound B and valproic acid, System suitability solution
Tailing fact o r: NMT 1.5, Standard solution
Relat ive s t andard deviat io n: NMT 1.0%, Standard solution
Analys is
Samples : Standard solution and Sample solution
Calculate the percentage of valproic acid (C8H16O2) in the portion of Valproic Acid taken:

Result = (rU/rS) × (CS/CU) × 100

rU = peak response from the Sample solution

rS = peak response from the Standard solution

CS = concentration of USP Valproic Acid RS in the Standard solution (mg/mL)

CU = concentration of Valproic Acid in the Sample solution (mg/mL)

Accept ance crit eria: 98.0%–102.0% on the anhydrous basis

IMPURIT IES
•R I 〈281〉: NMT 0.1%
•O I
Sys t em s uit abilit y s o lut io n: 0.1 µL/mL of USP Valproic Acid Related Compound A RS and 1.0 µL/mL each of butyric acid and valeric acid in Valproic Acid
Sample s o lut io n: Valproic Acid
C hro mat o graphic s ys t em
(See Chromatography 〈621〉, System Suitability.)
Mo de: GC
Det ect o r: Flame ionization
C o lumn: 0.32-mm × 60-m; coated with a 0.3-µm film of phase G25
Temperat ures
Inject io n po r t : 240°
Det ect o r: 260°
C o lumn: See Table 1.
 Table 1

Ho ld T ime at Final
Init ial Temperat ure (°) Temperat ure Ramp (°/min) Final Temperat ure (°) Temperat ure (min)

145 0 145 48

145 5 190 —

C arrier gas : Helium

Flo w rat e: 150 mL/min
Inject io n vo lume: 0.5 µL
Inject io n t ype: Split flow ratio, 100:1
Sys t em s uit abilit y
Sample: System suitability solution
[N —The relative retention times for butyric acid, valeric acid, valproic acid, and valproic acid related compound A are 0.38, 0.52, 1.0, and 1.64, respectively.]
Suit abilit y requirement s
Res o lut io n: NLT 23.0 between butyric acid and valeric acid
C o lumn effi ciency: NLT 100,000 theoretical plates for valeric acid
Tailing fact o r: NMT 1.5 for valeric acid
Ret ent io n t ime: The related compound A peak must elute between 41 and 50 min.
Peak area: The related compound A peak area must be NLT 0.01% relative to the valproic acid peak area.
Analys is
Sample: Sample solution
Calculate the percentage of each impurity in the portion of Valproic Acid (C8H16O2) taken:

Result = (rU/rT) × 100

rU = peak response for each impurity

rT = sum of the responses for all the peaks

Accept ance crit eria

Individual impurit ies : NMT 0.1%
To t al impurit ies : NMT 0.3%

SPEC IFIC T EST S

•W D 〈921〉, Method I: NMT 1.0%

ADDIT IONAL REQUIREMENT S

•P S : Preserve in tight glass, stainless steel, or polyethylene (HDPE) containers.
• USP R S 〈11〉
USP Valproic Acid RS
USP Valproic Acid Related Compound A RS
2-Allylpent-4-enoic acid;
Also known as Diallylacetic acid.
C8H12O2 140.18
USP Valproic Acid Related Compound B RS
2-Isopropylpentanoic acid;
Also known as (2RS)-2-(1-Methylethyl)pentanoic acid.
C8H16O2 144.21

Au xilia r y In fo r m a t io n - Please check for your question in the FAQs before contacting USP.

To pic/Ques t io n C o nt act Exper t C o mmit t ee

VALPROIC ACID Nicholas Garito Jr. CHM42015 Chemical Medicines Monographs 4

Scientific Liaison
+1 (301) 816-8321

Chroma t ogra phic Columns Inf orma t ion: Chromatographic Columns

Most Rec ent ly Appea red In:

Pharm ac ope ial Forum : Volum e No. 41(5)

Pa ge Inf orma t ion:

US P42-NF37 - 4532
US P41-NF36 - 4272
US P40-NF35 - 6644

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