What Are the Most Common Valproic Acid Side Effects?

Magnesium Valproate is used to treat all types of epilepsy. Magnesium valproate itself has certain toxic and side effects. The main side effects are gastrointestinal symptoms such as nausea, vomiting, diarrhea, and dysphagia, followed by adverse reactions such as muscle weakness, limb tremor, ataxia, drowsiness, confusion or coma .

Chinese name: Magnesium valproate

Chinese alias: 2-propyl magnesium valerate

English name: magnesium, 2-propylpentanoate

English alias: Magnesium valproate; Magnesium 2-propylvalerate; magnesium bis (2-propylpentanoate); EINECS 263-770-9; Magnesium dipropylacetate;

CAS number: 62959-43-7

Molecular formula: C ₁₆ H ₃₀ MgO ₄

Molecular weight: 310.71200

Exact mass: 310.19900

PSA: 52.60000

LogP: 4.42060 ^[1]

Appearance and properties: white powder

Boiling point: 220ºC at 760 mmHg

Flash point: 116.6ºC ^[1]

Valproate

Bingwusuanmei

Magnesium Valproate

C ₁₆ H ₃₀ MgO ₄

This product is magnesium 2-propylvalerate. Calculated based on the dry product, magnesium valproate should be 98.0% to 102.0%.

[ Properties ] This product is a white crystalline powder or granules with a slight smell of valproic acid.

The product is slightly soluble in dilute acid, slightly soluble in water and ethanol.

[ Identification ] Take about 0.1g of this product, add 10ml of water, heat to dissolve, add 1ml of benzene, 1 ~ 2 drops of 1% uranium acetate solution and 1 ~ 2 drops of rhodamine B saturated benzene solution, shake well, benzene layer That is pink, orange fluorescence under ultraviolet light.

Take about 2g of the product, add 50ml of water, heat to dissolve, let cool, add about 5ml of dilute sulfuric acid to make the solution acidic, add 15ml of ether, shake, place to separate the layers, and identify the magnesium salt in the aqueous solution (Appendix III).

(3) Take about 0.1g of the product, add 10ml of water, shake for 15 minutes, filter, evaporate the filtrate to dryness, and the infrared absorption spectrum of the residue should be consistent with the control spectrum (spectrum set 66).

[ Check ]

Alkalinity: Take 1.0g of this product, add 20ml of water to dissolve it, and measure it according to law (Appendix VI H). The pH value should be 8.0 ~ 10.0.

Take about 0.5g of the substance , put it in a separatory funnel, add 10ml of water, add 5ml of dilute sulfuric acid, shake, extract three times with dichloromethane, 20ml each time, combine the dichloromethane solutions, add an appropriate amount of anhydrous sodium sulfate, Shake, filter, evaporate the filtrate on a rotary evaporator (temperature does not exceed 30 ° C), add 10 ml of dichloromethane precisely, shake to dissolve the residue, take 1 ml in two precise amounts, and place one in a 10 ml measuring bottle. Add butyric acid internal standard solution accurately (weigh 5mg of butyric acid, add dichloromethane to dissolve and dilute to 100ml, shake well) 1ml, dilute to the mark with dichloromethane, shake well, and use as another test solution; In a 100ml volumetric flask, dilute to the mark with dichloromethane and shake well. Take 1ml precisely and place it in a 10ml volumetric flask, add 1ml of butyric acid internal standard solution, dilute to the mark with dichloromethane, shake well, and use it as a control solution. Take 20mg of 2-phenylethanol, place it in a 10ml volumetric flask, add dichloromethane to dissolve and dilute to the mark, shake well, take 1ml precisely, place in a 25ml volumetric flask, add precisely 1ml of the test solution, and dilute with dichloromethane To the mark, shake well, as a system suitability solution. According to gas chromatography (Appendix VE), a capillary column with polyethylene glycol 20000 as a stationary phase; column length 30m, inner diameter 0.53mm, film thickness 1.0 & micro; m; carrier gas is nitrogen, flow rate 8ml / min; column temperature Programmable temperature rise, starting temperature is 130 ° C, hold for 20 minutes, and then heat up to 200 ° C at a rate of 5 ° C per minute for 15 minutes; the detector is a hydrogen flame ionization detector; the inlet temperature is 220 ° C; The detector temperature was 220 ° C. Take the system suitability solution 1 & micro; l into the gas chromatograph and record the chromatogram. The resolution of the 2-phenylethanol peak and the valproic acid peak should be greater than 3.0. Take the reference solution 1 & micro; l and inject it into the gas chromatograph, adjust the detection sensitivity so that the peak height of the main component chromatographic peak is about 10% ~ 20% of the full range; and then accurately measure each of the test solution and the reference solution 1 & micro; l respectively. Fill the gas chromatograph and record the chromatogram to 3 times the retention time of the main peak. If there are impurity peaks in the chromatogram of the test solution, the chromatographic peaks less than 0.05% can be ignored. The ratio of the area of each impurity peak to the area of the internal standard peak must not be greater than the ratio of the peak area of the main component of the control solution to the area of the internal standard peak. 1.5 times.

The total area of the impurity peaks other than the solvent peak must not exceed 1.5% of the total peak area.

Take this product for moisture and measure it according to the moisture measurement method (Appendix M, first method A). The moisture content should not exceed 4.5%.

Take 1.0g of heavy metal , add 10ml of dilute hydrochloric acid and 20ml of water, heat to boil, let cool, place in a separatory funnel, add 15ml of ether, shake, and let stand to separate. Separate the water layer, add the ammonia test solution to neutrality, place it in a water bath to concentrate to 20ml, let it cool, add 2ml of acetate buffer solution (pH3.5), check according to law (Appendix H first method) Over 20 parts per million.

[ Content determination ] Take about 0.4g of this product, accurately weigh, add 50ml of water, add 30ml of ether after dissolution, potentiometric titration (Appendix A), use glass-saturated calomel electrode, and hydrochloric acid titration solution (0.1mol / L) titrated to pH 3.8, that is. Each 1ml of hydrochloric acid titration solution (0.1mol / L) is equivalent to 15.54mg of C ₁₆ H ₃₀ MgO ₄ .

[ Category ] Antiepileptic and antimanic drugs.

[ Storage ] Sealed and stored in a dry place.

[ Preparation ] Magnesium valproate tablets Magnesium valproate sustained-release tablets ^[2]