JPS5858465A - Method and apparatus for analizing of barbituric acid - Google Patents
Method and apparatus for analizing of barbituric acidInfo
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- JPS5858465A JPS5858465A JP15699581A JP15699581A JPS5858465A JP S5858465 A JPS5858465 A JP S5858465A JP 15699581 A JP15699581 A JP 15699581A JP 15699581 A JP15699581 A JP 15699581A JP S5858465 A JPS5858465 A JP S5858465A
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Abstract
Description
【発明の詳細な説明】
この発明は、ガスクロマトグラフィーによる血清中のパ
ルプロ酸の直接分析法ならびに分析装置に関する。DETAILED DESCRIPTION OF THE INVENTION The present invention relates to a method for directly analyzing palproic acid in serum by gas chromatography, and an analytical device.
パルプｌ酸は、そのす） ＋３ウム塩が抗てんかん剤と
して治療に用いられており、適切な治療を行うために投
与患者の血中におけるパルプロ酸の良度を測定するのが
望まれる。その測定法として、現在バイオイムノアッセ
イ法、ガスクロマトグラフ法が知られて−る。前者は操
作が容易であるものの分析コストが高く、後者は分析コ
ストが安いが血液試料をクロロホルムなどの有機溶媒で
の抽出値理し、遠心分離により有機溶媒と血液とを分離
し、その有機溶媒層を分析することを賛してぃた・
この発明は、かかる公知のガスクロマトグラフ法を改良
するためになされたもので、血清を抽出操作などの前処
理をすることな（、迅速て簡便Ｋかつ確実にパルプロ酸
の検出、定量を可能にしたものである。Pulproic acid (+3 um salt) is used for treatment as an anti-epileptic drug, and in order to provide appropriate treatment, it is desirable to measure the quality of pulproic acid in the blood of patients receiving it. Bioimmunoassay and gas chromatography are currently known as methods for measuring this. The former method is easy to operate, but the analysis cost is high, while the latter method is low, but the blood sample is extracted with an organic solvent such as chloroform, and the organic solvent and blood are separated by centrifugation. This invention was made to improve the known gas chromatography method, and it is a quick and simple way to analyze serum without pretreatment such as extraction. Moreover, it has made it possible to reliably detect and quantify palproic acid.
かくして、この発明によれば、血清試料の適量を直接ガ
スクロマトグラフに注入し、無機酸が塗布な−し含浸さ
れた保持体を充填した反応カラム中でカラ五ｌ１ｆＩＩ
Ｊ１８０〜２２ケＣにおいて反応させた後、分離カラム
を通過させ、分離されたパルプロ酸を水素炎イオン化検
出器で検出、定量することからなるパルプロ酸の分析方
法が提供される。さらに、上記反応カラムが分離カラム
の前段に組み入れられたガスクロマトグラフが提供され
る。Thus, according to the present invention, an appropriate amount of a serum sample is directly injected into a gas chromatograph, and the serum sample is directly injected into a reaction column packed with a carrier impregnated with an inorganic acid.
A method for analyzing pulproic acid is provided, which comprises reacting in J180-22keC, passing it through a separation column, and detecting and quantifying the separated pulproic acid with a flame ionization detector. Furthermore, a gas chromatograph is provided in which the reaction column described above is incorporated before a separation column.
この発明に用ｖする無機酸としては、鉱酸を含む種々の
無機酸が挙げられ、これらのうちリン酸を用いるのが好
ましい。The inorganic acids used in this invention include various inorganic acids including mineral acids, and among these, it is preferable to use phosphoric acid.
この発明にお−では、血清試料は抽出等の前処理に付す
ことなく直接ガスクロマトグラフに注入される。注入方
法としては、ガスクロマトグラフ用のマイクロシリンジ
の針先内での血清蛋白の凝固を防ぐため、サンドイツチ
法を適用するのが好まし−。すなわち、例えば無機酸と
してリン酸を用いる場合マイクロシリンジ番と血清試料
ｌμｌを採取するに当り、その前後を各ｌμｊの蒸留水
または１９１以上のリン酸含有蒸留水でサンドイッチし
て注入する方法が適用される。この際、ＩＩＧ以上のリ
ン酸含有蒸留水を使用する方が反応カラムの劣化防止に
好結果をもたらし好ましいことを見出した。In this invention, a serum sample is directly injected into a gas chromatograph without being subjected to any pretreatment such as extraction. As the injection method, it is preferable to apply the Sandersch method to prevent coagulation of serum proteins within the needle tip of a microsyringe for gas chromatography. That is, for example, when using phosphoric acid as the inorganic acid, when collecting 1 μl of a serum sample using a microsyringe, a method is applied in which the sample is sandwiched with 1 μj of distilled water or distilled water containing 191 or more phosphoric acid and then injected. be done. At this time, it has been found that it is preferable to use distilled water containing phosphoric acid of IIG or higher, as this results in good results in preventing deterioration of the reaction column.
次に、かかる試料はまず反応カラムに導入されるが、こ
の反応カラムはこの発明の方法ならびに装置における特
徴部分を構成するものである。この反応カラムは、ガラ
ス製などのチューブ冬こ加熱手段を付し、チューブ内に
無機酸の含浸ないし塗布した保持体を充填したものから
構成されている。The sample is then first introduced into a reaction column, which constitutes a distinctive part of the method and apparatus of the invention. This reaction column consists of a tube made of glass or the like, equipped with heating means, and filled with a holder impregnated or coated with an inorganic acid.
保持体としては、無機酸が塗布または含浸によって保持
され、かつ不活性なものであればよＶｌ。たとえば、シ
リカウール、シリカ粉末、ケイソウ土などが挙げられる
。そして保持体への無機酸の保持は、後述の実施例で例
示したような方法で行うことができる。ことにリン酸を
用いる場合には８〜１５％程度の水溶液として用いるの
が一般に好ましい。The holding body may be one that holds the inorganic acid by coating or impregnating it and is inert. Examples include silica wool, silica powder, diatomaceous earth, and the like. The inorganic acid can be retained on the carrier by a method as exemplified in the Examples below. In particular, when phosphoric acid is used, it is generally preferable to use it as an approximately 8-15% aqueous solution.
この反応カラムは、１８ Ｇ’ＣＩ！ｆ以上２２０”Ｃ
程度の範囲に維持して血清試料の処理を行うのが望まし
めことが判明した。This reaction column has 18 G'CI! f or more 220”C
It has been found that it is desirable to maintain a certain range of serum samples when processing serum samples.
この反応カラムでは、パルプロ酸ナトリウムとしてヒト
に投与された薬剤が、血清中で主にナトリウム塩として
存在するが、このナトリウム塩を遊離ｌ１１に導（反応
が行われる。これによって、以上の分離カラムでの分離
ならびに水素炎イオン化検出量での検出が容易にかつ確
実に行われることを保障する効果をもたらしたものと信
じられる。In this reaction column, the drug administered to humans as sodium palproate exists mainly as a sodium salt in serum, and this sodium salt is converted into free l11 (reaction takes place). It is believed that this has the effect of ensuring that separation by ionization and detection by flame ionization detection can be carried out easily and reliably.
な珈、前記の血清試料のガスクロマトグラフへの注入時
に＃！固防止のためエタノールを用いることが考えられ
るが、この発明では上記の反応カラムでエステル化の反
応が起り、定量分析上好ましくないことが判明している
ことを注記する。However, when injecting the serum sample into the gas chromatograph, #! Although it is conceivable to use ethanol to prevent solidification, it is noted that in the present invention, an esterification reaction occurs in the above-mentioned reaction column, which has been found to be unfavorable for quantitative analysis.
かかる反応カラムから不活性キャリヤーガス〔Ｎ２など
〕とともに通過させた分析成分は、通常のガスクロマト
グラフの経路を通過させる。すなわち、反応カラムに接
続された分離カラムを鮭で、検出量によってパルプロ酸
が検出される。定量は、標準試料で得た検量線をもとに
行うことができる。The analyte passed from such a reaction column with an inert carrier gas (such as N2) is passed through a conventional gas chromatograph path. That is, when a separation column connected to a reaction column is used for salmon, pulpoic acid is detected according to the detected amount. Quantification can be performed based on a calibration curve obtained with standard samples.
か（して、この発明の方法は極めて簡便な方法であるこ
とが理解されるであろう。また定量分析の精度などにお
りても全く満足すべきもので、この点実施例で説明する
。(Thus, it will be understood that the method of the present invention is an extremely simple method. Also, the accuracy of quantitative analysis is completely satisfactory, and this point will be explained in Examples.
次に、添付図面によりこの発明の分析装置につＶ・ての
説明を行う。Next, the analysis device of the present invention will be explained with reference to the accompanying drawings.
第１図はここの発明の装置の一具体例における導入部及
び反応カラムの接続状態を示す要部端面図である。第１
図において、（１）はクーりングフイン、１２１ｇ１ニ
ードルバルブ、（３）はセプタム及び（４）はスペーサ
ーであり、これらによって試料導入部が構成されている
。（６）は無機酸としてのりン酸を含浸したシリカウー
ル（５１を充填してなる反応力ラム（内径３諷φ、長さ
くｍ）＝ １５０■）であり、これらの周囲には加熱手
段となるヒーター（７）が付設されている。そして反応
カラム（６）は分離用のガラスカラム（８）Ｋ接続され
ている。なお、（９）はキャップナツト、（２）はジヨ
イントナツト、（社）は０−リング、（２）はワッシャ
ー、（至）はスプリングである。また（Ｃ）は２■であ
り（場は３ｍである。キャリヤーガスは（至）より導入
される。また、第１図におＶ−てガラスカラム（８）は
水素炎イオン化検出器、レコーダーに連結されてｉる。FIG. 1 is an end view of essential parts showing the connection state of an introduction part and a reaction column in a specific example of the apparatus of the present invention. 1st
In the figure, (1) is a cooling fin, 121g1 needle valve, (3) is a septum, and (4) is a spacer, which constitute a sample introduction section. (6) is a reaction force ram (inner diameter 3 mm, length m) filled with silica wool (51) impregnated with phosphoric acid as an inorganic acid, and around it is a heating means. A heater (7) is attached. The reaction column (6) is connected to a separation glass column (8)K. In addition, (9) is a cap nut, (2) is a joint nut, (Company) is an O-ring, (2) is a washer, and (to) is a spring. In addition, (C) is 2■ (the field is 3 m).The carrier gas is introduced from (to).In addition, in Fig. 1, the glass column (8) at i is connected to i.
第２図は、この発明の装置の他の具体例を示す概略図で
ある。第２図に畠−で、ガラスカラム（８）は二つの試
料導入部−を有し、一方の試料導入部（３１とガラスカ
ラム（８）との間には、反応カラム（６）が介設されて
いる。キャリアーガス（２）を切替パル１α番を通して
導入流路（２）又は反応カラム（６）へと導びかれる。FIG. 2 is a schematic diagram showing another specific example of the device of the present invention. As shown in Figure 2, the glass column (8) has two sample introduction parts, and a reaction column (6) is interposed between one sample introduction part (31) and the glass column (8). The carrier gas (2) is guided to the introduction channel (2) or the reaction column (6) through the switching pulse number 1α.
なお、（至）はカラムパス、面は検出器パス、（至）は
水素炎イオン化検出器、（至）はエレクトロメーター、
（２）はレコーダーであり、（２）は水素ガス、（２）
は空気をそれぞれ示す。In addition, (to) is column path, surface is detector path, (to) is hydrogen flame ionization detector, (to) is electrometer,
(2) is a recorder, (2) is hydrogen gas, (2)
indicate air, respectively.
次にこの発明を実施例によって説明する。Next, the present invention will be explained with reference to examples.
実施例
（１）装置
ガスクロマトグラフは島津製作所製ＧＣ−７ＡＰＴＦ型
を使用した。検出量は水素炎イオン化検出器で、データ
処理はクロマトパックＥ−１Ｂを使用した。Example (1) Apparatus A GC-7APTF model manufactured by Shimadzu Corporation was used as a gas chromatograph. Detection amount was measured using a hydrogen flame ionization detector, and data processing was performed using Chromatopack E-1B.
（２）反応カラム
反応カラムは長さ１５０ｍ、内径３■のガラスパイプ内
にシリカウールを０．２５９充填し、そのパイプ内ＫＩ
Ｏチリン酸水溶液３−を流し、窒素ガスを１分間３０−
の速高で流し、常温にて水を除去した。（第１図参照）
（３１分析条件
分離カラムは０．５ ｍ Ｘ ３ ｍφのガラスカラム
ニシマライトＴ Ｐ Ａ （テレフタル酸モノマー、６
０〜８０１ シュ）を担体とし、ｌＱｌＦＡＬ−Ｍ（ポ
リエステル系分配剤〕を添加したものを使用した。(2) Reaction column The reaction column is a glass pipe with a length of 150 m and an inner diameter of 3 cm, filled with 0.25% silica wool, and a KI inside the pipe.
Flow the O typhosphoric acid aqueous solution 3- and nitrogen gas for 1 minute 30-
The water was removed at room temperature. (See Figure 1) (31 Analysis conditions The separation column is a 0.5 m x 3 mφ glass column Nisimalite TPA (terephthalic acid monomer, 6
0 to 801 mm) was used as a carrier, and lQlFAL-M (polyester-based distributing agent) was added thereto.
分離カラム温度：１４０°Ｃ 検出器温度 ： ｌ ９０’Ｃ 反応カラム温度： １４０”Ｃ、１６０’Ｃ。Separation column temperature: 140°C Detector temperature: 90’C Reaction column temperature: 140"C, 160'C.
１８ケＣ，２００°Ｃ９
２２０’Ｃ
キャリヤーガス：窒素ガス、７ Ｑ ｗ４／ｆｎｉｎ（
４）試薬
パルプロ酸す）９ウムは、協和醗酵工業株式会社製を、
リン酸、カプリル酸、ジフェニル、クロロホルムなどは
和光純薬工業株式金社製をそれぞれ使用した。18 C, 200°C9 220'C Carrier gas: Nitrogen gas, 7 Q w4/fnin (
4) The reagent pulproic acid (9um) was manufactured by Kyowa Hakko Kogyo Co., Ltd.
Phosphoric acid, caprylic acid, diphenyl, chloroform, and the like were manufactured by Kinsha, Wako Pure Chemical Industries, Ltd., respectively.
（５）試料の調製
血清の検体はコントロール血清ｌ−にパルプロ酸ナトリ
ウム（酸として１６μｉ相当）、カプリル酸ナトリウム
（酸として３２＃ｆ相当）を添加し、これを検体用の試
料として用Ｖ−た。(5) Preparation of sample For the serum sample, add sodium pulproate (equivalent to 16μi as acid) and sodium caprylate (equivalent to 32#f as acid) to control serum l-, and use this as the sample for the test V- Ta.
（６）試料の注入
フルスケールｌＯμｌのマイクロシリンジでまずリン酸
水溶液ｌμｌを採取し、次に血清試料ｌμｌを吸い上げ
、再びリン酸水溶液ｌμｌを吸い上げて合計３μｌとし
、これをガスクロマトグラフの試料注入口より反応カラ
ム内に導入した。(6) Sample injection First collect 1 μl of the phosphoric acid aqueous solution with a full-scale 10 μl microsyringe, then suck up 1 μl of the serum sample, and then suck up 1 μl of the phosphoric acid aqueous solution again to make a total of 3 μl, and transfer this to the sample injection port of the gas chromatograph. was introduced into the reaction column.
なお、この方法によって導入する場合に使用するリン酸
水溶液の濃度とパルプロ酸の回収率の関係について、コ
ントロール血清に一定量のパルプロ酸を添加したものを
試料として調べた結果を？！４に示す。Furthermore, regarding the relationship between the concentration of the phosphoric acid aqueous solution used when introducing by this method and the recovery rate of pulproic acid, what are the results of investigating a control serum with a certain amount of pulproic acid added as a sample? ! 4.
一万、このような方法による水分の影醤を調べるため、
パルプロ酸と内標準物質としてのカプリル酸とを含む塩
基性試料を用１１／”％上１リン酸水溶液の代りに蒸留
水を用Ｖ・た注入方法を適用して、注入時間を１０分と
して５回注入した。10,000, In order to investigate the water shadow sauce by this method,
A basic sample containing pulpoic acid and caprylic acid as an internal standard was used. Distilled water was used instead of an 11% monophosphoric acid aqueous solution, and the injection time was 10 minutes. Injected 5 times.
その結果は表１に示した。The results are shown in Table 1.
（７） 反応カラムの温度と、パルプロ酸ナトリウム
及びカプリル酸ナトリウムの反応率
Ｑ、ＩＮの水酸化ナトリ９ム水溶液ｌ−にパルプロ酸１
６μり、カプリル酸３２μグを添加した試料（塩基性試
料）と、０． Ｉ Ｎの塩酸水溶液１ｊｉＣパルプロ１
１１６μ２とカプリル酸３２Ｉ４を添加した試料（酸性
試料）を用いて反応カラムの温度と反応率について検討
した。(7) The temperature of the reaction column, the reaction rate Q of sodium palproate and sodium caprylate,
A sample to which 6 μg of caprylic acid was added (basic sample) and 0.6 μg of caprylic acid were added. IN aqueous hydrochloric acid solution 1jiC Palpro 1
The temperature of the reaction column and the reaction rate were investigated using a sample to which 116 μ2 and caprylic acid 32I4 were added (acidic sample).
第２図に示したガスクロマトグラフは、試料注入口を２
個有し、これを１本のガラスカラムに接続し、−力の試
料注入口は酸性試料（標準試料）を注入した。他方は反
応カラムを取り付は塩基性試料を注入した。The gas chromatograph shown in Figure 2 has two sample injection ports.
This was connected to one glass column, and an acidic sample (standard sample) was injected into the sample injection port. The other was equipped with a reaction column and the basic sample was injected into it.
その結果は１表２に示した通りで、反応カラムの温度を
１８０”Ｃ以上で行うと、パルプロ酸ナトリウム、カプ
リル酸ナトリウムを反応するのに適して−た。The results are shown in Table 1 and Table 2. When the temperature of the reaction column was 180"C or higher, it was suitable for reacting sodium palproate and sodium caprylate.
ｔ８１ ＩＩ準試料での（り返し種度反応カラムを１
９０’Ｃに設定し、０．ＩＮＮ水酸ナナトリ９ム水溶液
ｌにパルプロ酸１６μｆとカプリル酸３２μ２を添加し
、パルプロ酸とカプリル酸のピーク面積比を求め、これ
をくり返し精度とした。その結果は表３に示したが、変
動係数は１．５％であった。t81 II quasi-sample (repeated species reaction column 1
Set to 90'C, 0. 16 .mu.f of pulproic acid and 32 .mu.2 of caprylic acid were added to 1 liter of an aqueous solution of 9m INN hydroxyl, and the peak area ratio of palproic acid and caprylic acid was determined, and this was used as the repeat accuracy. The results are shown in Table 3, and the coefficient of variation was 1.5%.
（９）パルプロ酸を添加した血清試料でのくり返し精度 上記（５）の試料を用いた結果は、表５の通りである。(9) Repeatability accuracy with serum samples added with palproic acid The results using the sample (5) above are shown in Table 5.
１１回測定でその変動係数は４．８５’Ｊで血清試料に
も充分使用できるものであった。The coefficient of variation after 11 measurements was 4.85'J, which was sufficient to be used for serum samples.
叫 患者血清の応用
実際の患者血清を応用し、さらに従来の抽出法と比較し
た。その結果は表６に示したが、従来法とこの発明の方
法は大差なり結果を示した。Application of patient serum We applied actual patient serum and compared it with conventional extraction methods. The results are shown in Table 6, and the conventional method and the method of this invention showed a large difference in results.
またパルプロ酸添加の血清と患者血清のクロマトグラム
を第３図及びＷＩ４図に示したが、妨害成分もなく、短
時間で分析できるものであった〔図中、ｑは内標準とし
てのカプリル酸（３２ｎｆ）を示し、Ｐはパルプロ酸（
１θＲｙ） を示し、鼠は血清中のパルプロ酸を示す
。〕。In addition, chromatograms of serum containing palproic acid and patient serum are shown in Figure 3 and Figure WI4, and there are no interfering components and analysis can be performed in a short time [In the figure, q is caprylic acid as an internal standard. (32nf), P is palproic acid (
1θRy), and rats indicate serum palproic acid. ].
表３ 標準試料でのくり返し精度
※パルプロ５１（１６臘２）詔よびカプリル酸（３２ｆ
ｉＰ）を含む塩基性水溶液（Ｉ ＩＩＩ ）を試料とし
た。Table 3 Repeatability accuracy using standard samples
A basic aqueous solution (I III ) containing iP) was used as a sample.
表 ５ 表 ６Table 5 Table 6
ｓ１図は、この発明の装置の一具体例における導入部及
び反応カラムの接続状態を示す要部端面図である。第２
図は、この発明の装置の他の具体例を示す概略図である
。第３図は、この発明の方法によって得られた標準試料
のクロマトグラムの一具体例を示すグラフである。第４
図は標準試料の代わりに患者血清を用％（ｓた第３図相
当図である。
向・・・反応カラム、（６）・−・シリカウール、１７
１−・・ヒーター （８）・・・ガラスカラム
、（９）・・・キャップナツト、 αｌ・・・シ“ヨイ
ントナット、■・・・Ｏ−リング、 ロ・・・ワ
ッシャー、α３・・・スプリング、α楊・・・切替バル
ブ、０５１・・・導入流路、Ｑｅ・・・カラムバス、
αη・・・検出器ハス、（至）・・・水素炎イオン
化検数ａ湯・・・エレクトロメーター、圓・・・レコー
ダー、 （２）・・・水素ガス、■・・・空気、
（ハ）・・・キャリアーガス。
第３図
一→ｗ４ｒ間（介）
第４図
一一一÷時間（分）Figure s1 is an end view of essential parts showing the connection state of the introduction part and the reaction column in a specific example of the apparatus of the present invention. Second
The figure is a schematic diagram showing another specific example of the device of the present invention. FIG. 3 is a graph showing a specific example of a chromatogram of a standard sample obtained by the method of the present invention. Fourth
The figure is a diagram equivalent to Figure 3 in which patient serum was used instead of the standard sample.
1-Heater (8)...Glass column, (9)...Cap nut, αl...Joint nut, ■...O-ring, Ro...Washer, α3...Spring , α Yang...Switching valve, 051...Introduction channel, Qe...Column bus,
αη...Detector lotus, (to)...Hydrogen flame ionization count a hot water...Electrometer, circle...Recorder, (2)...Hydrogen gas, ■...Air,
(c)...Carrier gas. Figure 3 between 1 and w4r (intermediate) Figure 4 111 ÷ time (minutes)
Claims (1)
機酸が塗布な−し含浸された保持体を充填した反応カラ
ム中でカラム温度約１８０〜２２Ｇ”ＣＫｍ−で反応さ
せた後、分離カラムを通過させ、分離されたパルプロ酸
を水素炎イオン化検出器で検出・定量することからなる
パルプロ酸の分析方法。 ２ 無機酸がリン酸である特許請求の範囲第１項記載の
分析方法。 λ 試料導入部、加熱手段を付した分離カラム、水素炎
イオン化検出器などを順次設けたガスクロマトグラフに
調−て、試料導入部と分離カラムとの間に、無機酸が塗
布ないし含浸された保持体を充填しかつ加熱手段を有す
る反応カラムを介設したことからなるパルプロ酸分折用
ガスクロマトグラフ装置。 ４、無機酸がリン酸である特許請求の範囲第３項記載の
装置。[Claims] 1. An appropriate amount of a serum sample is injected into a gas chromatograph and reacted at a column temperature of about 180 to 22 G''CKm- in a reaction column packed with a carrier impregnated with an inorganic acid. A method for analyzing palproic acid, which comprises passing through a separation column and detecting and quantifying the separated pulproic acid with a flame ionization detector. 2. Claim 1, wherein the inorganic acid is phosphoric acid. λ A gas chromatograph is equipped with a sample introduction section, a separation column equipped with a heating means, a flame ionization detector, etc., and an inorganic acid is applied or coated between the sample introduction section and the separation column. A gas chromatograph apparatus for analyzing pulpo acid, which comprises a reaction column filled with an impregnated carrier and equipped with a heating means. 4. The apparatus according to claim 3, wherein the inorganic acid is phosphoric acid. .
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP15699581A JPS5858465A (en) | 1981-10-01 | 1981-10-01 | Method and apparatus for analizing of barbituric acid |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP15699581A JPS5858465A (en) | 1981-10-01 | 1981-10-01 | Method and apparatus for analizing of barbituric acid |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPS5858465A true JPS5858465A (en) | 1983-04-07 |
| JPH0330818B2 JPH0330818B2 (en) | 1991-05-01 |
Family
ID=15639873
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP15699581A Granted JPS5858465A (en) | 1981-10-01 | 1981-10-01 | Method and apparatus for analizing of barbituric acid |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPS5858465A (en) |
Cited By (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2014035275A (en) * | 2012-08-09 | 2014-02-24 | Shimadzu Corp | Gas chromatograph |
| CN108132312A (en) * | 2017-12-28 | 2018-06-08 | 北京和合医学诊断技术股份有限公司 | Detect the liquid phase chromatography analytical method of valproic acid medicament contg in blood |
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| 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 |
| CN109580828A (en) * | 2018-12-28 | 2019-04-05 | 四川健能制药有限公司 | A kind of related substance-measuring method of sodium vedproate oral administration solution |
| CN110646559A (en) * | 2019-11-12 | 2020-01-03 | 北京和合医学诊断技术股份有限公司 | Method for detecting valproic acid in blood |
| CN111257440A (en) * | 2019-12-25 | 2020-06-09 | 四川健能制药有限公司 | GC-HS-based method for determining potential genotoxic impurities in sodium valproate |
-
1981
- 1981-10-01 JP JP15699581A patent/JPS5858465A/en active Granted
Cited By (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2014035275A (en) * | 2012-08-09 | 2014-02-24 | Shimadzu Corp | Gas chromatograph |
| CN108132312A (en) * | 2017-12-28 | 2018-06-08 | 北京和合医学诊断技术股份有限公司 | Detect the liquid phase chromatography analytical method of valproic acid medicament contg in blood |
| CN108469488A (en) * | 2018-05-30 | 2018-08-31 | 北京和合医学诊断技术股份有限公司 | Detect the liquid phase chromatography analytical method of content of valproic acid in blood |
| 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 |
| CN109580828A (en) * | 2018-12-28 | 2019-04-05 | 四川健能制药有限公司 | A kind of related substance-measuring method of sodium vedproate oral administration solution |
| CN109580831B (en) * | 2018-12-28 | 2022-05-13 | 四川健能制药有限公司 | Method for measuring related substances of sodium valproate oral solution |
| CN110646559A (en) * | 2019-11-12 | 2020-01-03 | 北京和合医学诊断技术股份有限公司 | Method for detecting valproic acid in blood |
| CN111257440A (en) * | 2019-12-25 | 2020-06-09 | 四川健能制药有限公司 | GC-HS-based method for determining potential genotoxic impurities in sodium valproate |
Also Published As
| Publication number | Publication date |
|---|---|
| JPH0330818B2 (en) | 1991-05-01 |
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