CN111398099A - Method for rapidly determining content of sodium valproate in sodium valproate for injection - Google Patents
Method for rapidly determining content of sodium valproate in sodium valproate for injection Download PDFInfo
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- CN111398099A CN111398099A CN202010263328.8A CN202010263328A CN111398099A CN 111398099 A CN111398099 A CN 111398099A CN 202010263328 A CN202010263328 A CN 202010263328A CN 111398099 A CN111398099 A CN 111398099A
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- sodium valproate
- injection
- precisely
- valproate
- sodium
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- AEQFSUDEHCCHBT-UHFFFAOYSA-M sodium valproate Chemical compound [Na+].CCCC(C([O-])=O)CCC AEQFSUDEHCCHBT-UHFFFAOYSA-M 0.000 title claims abstract description 88
- NIJJYAXOARWZEE-UHFFFAOYSA-N di-n-propyl-acetic acid Natural products CCCC(C(O)=O)CCC NIJJYAXOARWZEE-UHFFFAOYSA-N 0.000 title claims abstract description 87
- 229940084026 sodium valproate Drugs 0.000 title claims abstract description 87
- 238000000034 method Methods 0.000 title claims abstract description 34
- 238000002347 injection Methods 0.000 title claims abstract description 25
- 239000007924 injection Substances 0.000 title claims abstract description 25
- 239000008367 deionised water Substances 0.000 claims abstract description 21
- 229910021641 deionized water Inorganic materials 0.000 claims abstract description 21
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 21
- 239000012488 sample solution Substances 0.000 claims abstract description 16
- 230000003204 osmotic effect Effects 0.000 claims abstract description 11
- 239000012086 standard solution Substances 0.000 claims description 14
- 238000005303 weighing Methods 0.000 claims description 9
- 238000013495 osmolality determination method Methods 0.000 claims description 6
- 239000003814 drug Substances 0.000 description 12
- 239000000523 sample Substances 0.000 description 8
- 206010010904 Convulsion Diseases 0.000 description 5
- 238000001514 detection method Methods 0.000 description 4
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
- 239000001961 anticonvulsive agent Substances 0.000 description 3
- 238000005259 measurement Methods 0.000 description 3
- 238000011084 recovery Methods 0.000 description 3
- 239000002904 solvent Substances 0.000 description 3
- 208000036572 Myoclonic epilepsy Diseases 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- 201000009028 early myoclonic encephalopathy Diseases 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 206010015037 epilepsy Diseases 0.000 description 2
- 239000013558 reference substance Substances 0.000 description 2
- 239000000243 solution Substances 0.000 description 2
- 206010053164 Alcohol withdrawal syndrome Diseases 0.000 description 1
- 102000004506 Blood Proteins Human genes 0.000 description 1
- 108010017384 Blood Proteins Proteins 0.000 description 1
- 206010008748 Chorea Diseases 0.000 description 1
- 208000012661 Dyskinesia Diseases 0.000 description 1
- 208000002091 Febrile Seizures Diseases 0.000 description 1
- 208000034308 Grand mal convulsion Diseases 0.000 description 1
- 208000007514 Herpes zoster Diseases 0.000 description 1
- 206010021750 Infantile Spasms Diseases 0.000 description 1
- 208000002193 Pain Diseases 0.000 description 1
- 206010034759 Petit mal epilepsy Diseases 0.000 description 1
- 241000097929 Porphyria Species 0.000 description 1
- 208000010642 Porphyrias Diseases 0.000 description 1
- 208000006633 Tonic-Clonic Epilepsy Diseases 0.000 description 1
- 208000028311 absence seizure Diseases 0.000 description 1
- 210000004100 adrenal gland Anatomy 0.000 description 1
- 208000029650 alcohol withdrawal Diseases 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 230000008485 antagonism Effects 0.000 description 1
- 229960003965 antiepileptics Drugs 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 208000012601 choreatic disease Diseases 0.000 description 1
- 230000036461 convulsion Effects 0.000 description 1
- 208000013257 developmental and epileptic encephalopathy Diseases 0.000 description 1
- 238000007865 diluting Methods 0.000 description 1
- 238000004090 dissolution Methods 0.000 description 1
- 230000007613 environmental effect Effects 0.000 description 1
- 201000002933 epilepsy with generalized tonic-clonic seizures Diseases 0.000 description 1
- 230000001037 epileptic effect Effects 0.000 description 1
- 229960002767 ethosuximide Drugs 0.000 description 1
- HAPOVYFOVVWLRS-UHFFFAOYSA-N ethosuximide Chemical compound CCC1(C)CC(=O)NC1=O HAPOVYFOVVWLRS-UHFFFAOYSA-N 0.000 description 1
- 210000003722 extracellular fluid Anatomy 0.000 description 1
- 206010016284 febrile convulsion Diseases 0.000 description 1
- 230000006589 gland dysfunction Effects 0.000 description 1
- 238000004128 high performance liquid chromatography Methods 0.000 description 1
- 238000010255 intramuscular injection Methods 0.000 description 1
- 239000007927 intramuscular injection Substances 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 230000002151 myoclonic effect Effects 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 201000000980 schizophrenia Diseases 0.000 description 1
Classifications
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N13/00—Investigating surface or boundary effects, e.g. wetting power; Investigating diffusion effects; Analysing materials by determining surface, boundary, or diffusion effects
- G01N13/04—Investigating osmotic effects
Abstract
The invention discloses a method for rapidly determining the content of sodium valproate in sodium valproate for injection, which comprises the following steps of taking a bottle of sodium valproate for injection, precisely adding deionized water to dissolve the sodium valproate for injection to prepare a sodium valproate sample solution to be detected with a certain concentration, precisely transferring the sodium valproate sample solution to be detected with the concentration of 50 mu L, determining the osmotic pressure molar concentration value of the sodium valproate sample solution to be detected, and calculating the content of sodium valproate in sodium valproate for injection according to a formula (1).
Description
Technical Field
The invention relates to the field of medicine detection, in particular to a method for determining the content of sodium valproate in sodium valproate for injection by adopting an osmotic pressure molar concentration method.
Background
Valproic acid sodium is a nitrogen-free broad-spectrum antiepileptic drug. The medicine has different degrees of antagonism to convulsion caused by various methods. It is effective on various epilepsy such as small seizures, myoclonic epilepsy, local seizures, grand mal epilepsy and mixed epilepsy. The drug is mainly distributed in extracellular fluid, and most of the drug is combined with plasma protein in blood. It is mainly used for various epileptics with ineffective antiepileptic drugs, especially for small seizures.
Sodium valproate is the first choice for primary grand attacks and absence grand attacks, and has poor curative effect on partial attacks (simple partial attacks and complex partial attacks and grand attacks secondary to the partial attacks). It has certain curative effect on benign myoclonic epilepsy and infantile spasm, and can be used for treating myoclonic absence seizure by adding ethosuximide or other antiepileptic drugs. The composition can be used for treating febrile convulsion, dyskinesia, chorea, porphyria, schizophrenia, pain caused by herpes zoster, adrenal gland dysfunction, and preventing alcohol withdrawal syndrome.
The medicine is mainly prepared by intramuscular injection. The content determination of sodium valproate in the medicine is particularly important. The existing method for measuring the content of sodium valproate for injection adopts a measuring method disclosed in the second part of national standard 'Chinese pharmacopoeia' 2015 edition, namely the method for measuring the content of sodium valproate for injection is a high performance liquid method, firstly, the mobile phase of the method contains acetonitrile with a high proportion (30%), and the problems of poor environmental protection and medicament pollution to the environment exist; secondly, the method needs to carry out pretreatment on the sample, and the reference substance is measured by the same method, so that the method has the problems of high cost and long analysis time.
Disclosure of Invention
In order to solve the technical problems, the invention provides the method for measuring the content of the sodium valproate medicine for injection, which is simple and quick, simple in sample treatment, environment-friendly and high in accuracy.
In order to achieve the purpose, the invention adopts the technical scheme that: a method for rapidly determining the content of sodium valproate in sodium valproate for injection comprises the following steps:
1) a bottle of sodium valproate for injection is precisely added with deionized water to be dissolved to prepare a sodium valproate sample solution to be tested with a certain concentration, preferably, the concentration of the sodium valproate sample solution to be tested is 18-22mg/m L.
2) Accurately transferring 50 mu L of the sodium valproate sample solution to be tested obtained in the step 1), determining the osmotic pressure molar concentration value of the sodium valproate sample solution to be tested, and calculating the content of sodium valproate in the sodium valproate for injection according to the formula (1);
wherein the osmolality determination unit is: mOsmol kg-1；
V volume of deionized water added (m L);
N＝2.03。
further, the method comprises the steps of weighing 18-22mg of sodium valproate standard, precisely weighing, precisely adding deionized water 1m L to dissolve, shaking up to obtain a sodium valproate standard solution, precisely transferring 50 mu L of the sodium valproate standard solution, measuring the osmotic pressure molar concentration value of the sodium valproate standard solution, and calculating the coefficient N according to the formula (2);
wherein the osmolality determination unit is: mOsmol kg-1；
And m is the mass of sodium valproate.
Preferably, at least 10 samples of the sodium valproate standard solution are prepared, measured 10 times, and averaged to obtain the coefficient N.
The invention has the beneficial effects that:
1. in the determination method, the appropriate concentration of sodium valproate is about 20mg/m L, deionized water is used as a solvent, the sample can be processed only by diluting the medicine with the deionized water, the sample is simple to process, the solvent is the deionized water, and the whole detection process has no organic solvent and does not pollute the environment.
2. The invention obtains the conversion constant N of the sodium valproate content and the osmotic pressure molar concentration value thereof under the condition that the concentration of the sodium valproate is about 20mg/m L by a scientific means, and confirms the accuracy of the method by researches such as interference tests, recovery rate tests, precision tests and the like.
3. The invention has simple sample pretreatment and short determination time. The sample only needs one-step pretreatment and is directly dissolved by deionized water with a certain volume, and the determination time only needs ten seconds.
4. The invention has low cost, does not need reference substances, and can be obtained by substituting the result into a formula for calculation.
Detailed Description
A method for rapidly determining the content of sodium valproate in sodium valproate for injection comprises the following steps:
1) a bottle of sodium valproate for injection is precisely added with deionized water to be dissolved to prepare a sodium valproate sample solution to be tested with the concentration of 18-22mg/m L.
2) Accurately transferring 50 mu L of the sodium valproate sample solution to be tested obtained in the step 1), determining the osmotic pressure molar concentration value of the sodium valproate sample solution to be tested, and calculating the content of sodium valproate in the sodium valproate for injection according to the formula (1);
wherein the osmolality determination unit is: mOsmol kg-1；
V volume of deionized water added (m L);
N＝2.03。
example 1
The instrument comprises the following steps: tianjin Tianhe medical instruments GmbH, model SMC-30C
Interference of (I) solvent deionized water on rapid determination of sodium valproate content for injection
Deionized water 50 mu L is precisely measured, the osmotic pressure molar concentration is measured, and the result is 0.
(II) method for obtaining N2.03 in formula (1)
Sodium valproate standard: the purity is 99.8 percent
The method comprises the following steps: sodium valproate standard (m) was weighed as in Table 11) Precisely weighing about 20mg of sodium valproate standard solution, precisely adding deionized water of 1m L to dissolve, and shaking up to obtain sodium valproate standard solution, precisely weighing 50 mu L of sodium valproate standard solution, measuring the osmotic pressure molar concentration value of the sodium valproate standard solution, and calculating the coefficient N according to the formula (2);
m is the mass of sodium valproate, and m is m in the embodiment1× purity ═ m1×99.8％。
TABLE 1
As shown in table 1, in formula (1), N is 2.03.
(III) precision of measurement
Sodium valproate standard: the purity is 99.8 percent
The instrument comprises the following steps: tianjin Tianhe medical instruments GmbH, model SMC-30C
1. Accurately weighing 19.77mg of sodium valproate standard, precisely adding deionized water 1m L to dissolve, shaking uniformly, precisely weighing 50 mu L, measuring the osmolality value, and repeating the test for 6 times to obtain the osmolality value with RSD of 0.2%.
2. Commercially available sodium valproate medicine for injection (specification 0.4g) is prepared by precisely adding deionized water 20m L into 1 tube, dissolving and shaking uniformly, precisely measuring 50 μ L, measuring the osmolality value, and repeating the test for 6 times to obtain the osmolality value with RSD of 0.3%.
Therefore, the method of the invention has good precision and can ensure the accuracy of the measurement result.
(IV) measurement accuracy
1) Weighing sodium valproate standard (m)1) About 18mg, 20mg and 22mg, 3 parts of each are precisely weighed, precisely added with deionized water of 1m L for dissolution and shaken up to obtain the sodium valproate standard solution.
2) Precisely measuring 50 mu L of the sodium valproate standard solution obtained in the step 1), respectively measuring the osmotic pressure molar concentration values, and calculating the detection amount of sodium valproate according to a formula (3), wherein the results are shown in Table 2.
TABLE 2
As can be seen from Table 2, the average recovery using the process of the invention was 100.05%, indicating a concentration of about 20mg m L-1About, the recovery rate is good, and meanwhile, the qualified range of the content of the sodium valproate in the reference legal standard is 90-110%, so the method is preferred, and the concentration of the sodium valproate in the sample solution is measured to be 18-22mg/m L optimally.
Example 2 application
A method for rapidly determining the content of sodium valproate in sodium valproate for injection comprises the following steps:
1) commercially available sodium valproate medicine for injection (specification is 0.4g), 1 piece of the medicine is precisely added with deionized water 20m L and shaken up to obtain a sodium valproate sample solution to be tested.
2) Precisely transferring 50 mu L of the solution to be tested of the sodium valproate sample obtained in the step 1), measuring the osmotic pressure molar concentration value of the solution, and calculating the content of the sodium valproate in the sodium valproate for injection according to the formula (1);
wherein the osmolality determination unit is: mOsmol kg-1；
V-volume of deionized water added (20m L);
N＝2.03。
15 cases of sodium valproate for injection were measured, and the results are shown in Table 3 by using the method of the present invention and the high performance liquid chromatography disclosed in the second part of the "Chinese pharmacopoeia" 2015 edition, respectively.
TABLE 3
As can be seen from Table 3, the method of the present invention has the advantages of accurate result, simple sample treatment, simple and rapid detection method, and high accuracy.
Claims (4)
1. A method for rapidly determining the content of sodium valproate in sodium valproate for injection is characterized by comprising the following steps of:
1) taking a bottle of sodium valproate for injection, and precisely adding deionized water to dissolve the sodium valproate to prepare a sodium valproate sample solution to be detected with a certain concentration;
2) accurately transferring 50 mu L of the sodium valproate sample solution to be tested obtained in the step 1), determining the osmotic pressure molar concentration value of the sodium valproate sample solution to be tested, and calculating the content of sodium valproate in the sodium valproate for injection according to the formula (1);
wherein the osmolality determination unit is: mOsmol kg-1；
V is the volume of deionized water added precisely (m L);
N＝2.03。
2. the method as claimed in claim 1, wherein in step 1), the concentration of the sodium valproate sample solution to be tested is 18-22mg/m L.
3. The method according to claim 1 or 2, wherein the N-2.03 is obtained by weighing 18-22mg of sodium valproate standard, precisely weighing, precisely adding deionized water 1m L to dissolve, shaking up to obtain a sodium valproate standard solution, precisely transferring 50 μ L of the sodium valproate standard solution, measuring the osmolality value of the sodium valproate standard solution, and calculating the coefficient N according to the formula (2);
wherein the osmolality determination unit is: mOsmol kg-1；
And m is the mass of sodium valproate.
4. The method of claim 3, wherein the sodium valproate standard solution is prepared into at least 10 samples, measured 10 times, and averaged to obtain the factor N.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202010263328.8A CN111398099A (en) | 2020-04-07 | 2020-04-07 | Method for rapidly determining content of sodium valproate in sodium valproate for injection |
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| Application Number | Priority Date | Filing Date | Title |
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| CN202010263328.8A CN111398099A (en) | 2020-04-07 | 2020-04-07 | Method for rapidly determining content of sodium valproate in sodium valproate for injection |
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Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20080081069A1 (en) * | 2006-09-28 | 2008-04-03 | Lupin Limited | Novel controlled release formulations of divalproex sodium |
| CN103454369A (en) * | 2013-09-09 | 2013-12-18 | 上海兰卫临床检验有限公司 | Method for detecting sodium valproate content of blood through high performance liquid chromatography |
| CN109580831A (en) * | 2018-12-28 | 2019-04-05 | 四川健能制药有限公司 | Method for measuring related substances of sodium valproate oral solution |
-
2020
- 2020-04-07 CN CN202010263328.8A patent/CN111398099A/en active Pending
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20080081069A1 (en) * | 2006-09-28 | 2008-04-03 | Lupin Limited | Novel controlled release formulations of divalproex sodium |
| CN103454369A (en) * | 2013-09-09 | 2013-12-18 | 上海兰卫临床检验有限公司 | Method for detecting sodium valproate content of blood through high performance liquid chromatography |
| CN109580831A (en) * | 2018-12-28 | 2019-04-05 | 四川健能制药有限公司 | Method for measuring related substances of sodium valproate oral solution |
Non-Patent Citations (2)
| Title |
|---|
| 张迪等: "冰点下降法快速测定门冬氨酸钾注射液的含量", 《药物分析杂志》 * |
| 黄剑英等: "HPLC测定丙戊酸钠注射液中丙戊酸钠的含量", 《中国现代应用药学》 * |
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Application publication date: 20200710 |
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