What Is Sodium Valproate?

Valproate is a nitrogen-free, broad-spectrum antiepileptic drug. This product has different degrees of resistance to convulsions caused by various methods. It is effective for all types of epilepsy in humans, such as small seizures, myoclonic epilepsy, localized seizures, large seizures and mixed epilepsy. Oral absorption is fast and complete, mainly distributed in extracellular fluid, and most of it binds to plasma proteins in the blood. It is mostly used in patients with various types of epilepsy who are not effective with other antiepileptic drugs, especially small hair.

Chinese name: Sodium valproate

Chinese alias: Sodium 2-propylvalerate; Dibai spasm;

English name: sodium valproate

English alias: sodium, 2-propylpentanoate; 2-Propylpentanoic acid, sodium salt; Sodium 2-Propylvalerate; Sodium 2-Propylpentanoate; Sodium 2-propylpentanoate;

CAS number: 1069-66-5

Molecular formula: C ₈ H ₁₅ NaO ₂

Molecular weight: 166.19300

Exact mass: 166.09700

PSA: 40.13000

LogP: 0.95270 ^[1]

Appearance and properties: white powder

Melting point: 300 ° C

Boiling point: 220ºC at 760 mmHg

Flash point: STABILITY

Water solubility: soluble

Stability: Stable under normal temperatures and pressures.

Storage conditions: Store in a cool, dry place. Store in a tightly closed container.

Vapor pressure: 0.0435mmHg at 25 ° C ^[1]

Packing level: III

Hazard category: 6.1 (b)

Customs code: 2915900090

Dangerous Goods Transport Code: 2811

WGK Germany: 3

Danger category code: R22; R36 / 38; R61

Safety instructions: S36 / 37-S53-S45-S37 / 39-S26

RTECS number: YV7876000

Dangerous goods mark: T ^[1]

From diethyl malonate as raw material. ^[1]

Basic introduction of sodium valproate

Name: Sodium valproate

English name: Sodium Valproate

Alias: Sodium Dimalonate

Chemical name: Sodium 2-propylvalerate

Category: Antiepileptic drugs

Properties: This product is a white sugar-coated tablet, which is white or almost white after removing the sugar coating. ^[1]

Valproic acid function and indications

This medicine is the first choice for primary major episodes and minor absence episodes, and has a poor effect on partial episodes (simple partial episodes, complex partial episodes, and secondary episodes of partial episodes). It has a certain effect on benign myoclonic epilepsy and infantile spasms, and it is effective to add ethosuccinine or other antiepileptic drugs to myoclonic absence. Can be used for refractory epilepsy. In addition to anti-epilepsy, the drug can also be used to treat febrile seizures, dyskinesia, chorea, porphyria, schizophrenia, herpes-induced pain, adrenal dysfunction, and prevention of alcohol withdrawal syndrome. ^[2]

Valproic acid drug analysis

Method name: Sodium Valproate-Determination of Valproate-Potentiometric Titration

Scope of application: This method uses the titration method to determine the content of sodium valproate in the raw materials of sodium valproate.

This method is applicable to sodium valproate API.

Principle of the method: The test sample was dissolved in water and then ether was added. The potentiometric titration method was carried out using a glass-saturated calomel electrode and hydrochloric acid titrant. The content of sodium valproate was calculated according to the amount of titrant used.

Reagent: 1. Ether

2. Hydrochloric acid titration solution (0.1mol / L)

3.Methyl red-bromocresol green mixed indicator liquid

4. Reference anhydrous sodium carbonate

Equipment: Potentiometric Titrator

Sample preparation: 1. Hydrochloric acid titration solution (0.1mol / L)

Preparation: Take 9.0mL of hydrochloric acid, add an appropriate amount of water to 1000mL, and shake to obtain a 0.1mol / L hydrochloric acid titration solution.

Calibration: Take about 0.15g of reference anhydrous sodium carbonate dried to constant weight at 270 ~ 300 , accurately weigh, add 50mL of water to dissolve, add 10 drops of methyl red-bromocresol green mixed indicator liquid, titrate with this liquid When the solution changes from green to purple, boil for 2 minutes, cool to room temperature, and continue titration until the solution changes from green to dark purple. Each 1mL hydrochloric acid titration solution (0.1mol / L) is equivalent to 5.30mg of anhydrous sodium carbonate. Calculate the concentration of this solution based on the consumption of this solution and the amount of anhydrous sodium carbonate taken.

2. Methyl red-bromocresol green mixed indicator liquid

Take 20 mL of 0.1% methyl red ethanol solution, add 30 mL of 0.2% bromocresol green ethanol solution, and shake well.

Operation steps: Precisely weigh about 0.5g of the test sample, add 30mL of water to dissolve, add 30mL of diethyl ether, according to potentiometric titration, use glass-saturated calomel electrode, and titrate with hydrochloric acid titrant (0.1mol / L) to pH 4.5. Each 1 mL of hydrochloric acid titration solution (0.1 mol / L) is equivalent to 16.62 mg of C ₈ H ₁₅ NaO ₂ .

Note: "Precision weighing" means that the weighed weight should be accurate to one thousandth of the weighed weight. "Precision measurement" means that the accuracy of measuring the volume should meet the accuracy requirements of the volume pipette in national standards. ^[2]

Dosage and value of sodium valproate

Usual dose for adults: Take 2 to 3 times daily by weight of 15mg / kg or 600 ~ 1200mg daily. Press 5-10 mg / kg at the beginning and increase it one week later until the seizure can be controlled. It should be taken in portions when the daily dosage exceeds 2500mg to reduce gastrointestinal irritation. The maximum daily amount is based on body weight not exceeding 30 mg / kg, or 1.8 to 2.4 g per day. Commonly used amount in children: same as adult by weight, can also be taken 20 ~ 30mg / kg daily, divided into 2 ~ 3 times or 15 mg / kg daily, increase by 5 ~ 10 mg / kg every other week as needed to be effective Or intolerance so far. ^[2]

Adverse reactions to valproate

1. Common adverse reactions are diarrhea, indigestion, nausea, vomiting, gastrointestinal spasm, and can cause changes in the menstrual cycle.

2. Rarely, transient hair loss, constipation, drowsiness, dizziness, fatigue, headache, ataxia, mild tremor, abnormal excitement, restlessness and irritability.

3. Occasionally long-term use of pancreatitis and acute liver necrosis.

4. It can make thrombocytopenia cause purpura, bleeding and prolonged bleeding time. Blood phase should be checked regularly.

5. It has damage to liver function and causes elevation of serum alkaline phosphatase and aminotransferase. Check liver function for 2 months.

6. Occasionally allergies.

7. Occasional hearing loss and reversible hearing damage. ^[2]

Precautions for sodium valproate

1. Avoid drinking alcohol during medication, drinking can increase the sedative effect.

2. Withdrawal should be gradually reduced to prevent recurrence; when replacing other anticonvulsants, the amount of this product should be gradually increased, and the amount of the replaced drug should be gradually reduced.

3. In the surgical department or other emergency treatment, the prolonged time that may be encountered, or the enhancement of the role of central nervous system inhibitors should be considered.

4. Before and during the medication, a complete blood cell (including platelet) count and liver and kidney function tests should be performed regularly.

5. Disturbance to diagnosis, false positives may occur in urine ketone test, and thyroid function test may be affected.

6. May slightly increase lactate dehydrogenase, alanine aminotransferase, aspartate aminotransferase and suggest asymptomatic liver poisoning. A possible increase in serum bilirubin indicates a potential severe liver poisoning. ^[2]

Valproic acid preparation specifications

1. Tablets: 200mg, Debakin sustained-release tablets 500mg (each tablet contains 333mg sodium valproate, 145mg valproic acid).

2. Syrup: 300ml (40mg / ml).

3. Injection: Each bottle contains 400mg of near-white sterile sodium valproate lyophilized powder, accompanied by a 4ml water for injection. Each bottle of depakin intravenous injection can only be used as a single dose. It must be prepared fresh before use and used within 24 hours. If it is not used, it should be discarded. ^[2]

Valproate manufacturers

Beijing Shuanghe Pharmaceutical Co., Ltd., Hangzhou Sanofi Shengdrabao Minsheng Pharmaceutical Co., Ltd., Northeast Pharmaceutical Group Shenyang Yanfeng Pharmaceutical Factory, Shandong Junan Pharmaceutical Factory, Hunan Xiangzhong Pharmaceutical Co., Ltd., Xi'an Fourth Pharmaceutical Factory , Jiangsu Hengrui Pharmaceutical Co., Ltd., Shandong Fangming Pharmaceutical Co., Ltd., Lianyungang Hengrui Pharmaceutical Co., Ltd., etc. ^[2]