CN116660430B - 一种盐酸环苯扎林缓释胶囊的检测方法 - Google Patents
一种盐酸环苯扎林缓释胶囊的检测方法 Download PDFInfo
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- JURKNVYFZMSNLP-UHFFFAOYSA-N cyclobenzaprine Chemical compound C1=CC2=CC=CC=C2C(=CCCN(C)C)C2=CC=CC=C21 JURKNVYFZMSNLP-UHFFFAOYSA-N 0.000 claims abstract description 8
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- B01D15/26—Selective adsorption, e.g. chromatography characterised by the separation mechanism
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Abstract
本发明涉及环苯扎林药品检测技术领域,具体为一种盐酸环苯扎林缓释胶囊的检测方法,包括如下步骤:取一份标准规格的盐酸环苯扎林缓释胶囊溶解在甲醇溶剂中,制备一种能够有效萃取盐酸环苯扎林缓释胶囊药品中活性组分盐酸环苯扎林的新型固相萃取膜,并把该固相萃取膜加入到上述溶液中,室温下振荡吸附,取出固相萃取膜,采用浓度NaOH溶液振荡解吸附,经氮气吹干之后利用流动相复溶,利用HPLC检测环苯扎林。本发明提供了一种能够有效萃取盐酸环苯扎林缓释胶囊药品中活性组分盐酸环苯扎林的新方法。
Description
技术领域
本发明涉及环苯扎林药品检测技术领域,具体为一种盐酸环苯扎林缓释胶囊的检测方法。
背景技术
盐酸环苯扎林(N,N-二甲基-3-(5H-二苯并[a,d]环庚三烯-5-亚基)-1-丙胺盐酸盐),是一种中枢性肌肉松弛药,临床上主要用作治疗疼痛性局部肌肉痉挛的辅助用药。盐酸环苯扎林缓释胶囊主要包括15mg胶囊1粒、30mg胶囊1粒两种规格。
在盐酸环苯扎林缓释胶囊药品检测分析过程中,由于活性组分盐酸环苯扎林的含量较低且盐酸环苯扎林缓释胶囊样品基质较为复杂,很难直接进行检测,因此需要对样品进行一定的预处理,使活性组分盐酸环苯扎林得到有效的分离和富集。而固相萃取法是一种基于液相色谱分离原理的样品预处理手段。
发明内容
本发明提供一种能够有效萃取盐酸环苯扎林缓释胶囊药品中活性组分盐酸环苯扎林的方法,并且把萃取得到的环苯扎林活性组分利用HPLC进行检测;
基于上述技术目的,本发明提供了如下具体的技术方案:
一种盐酸环苯扎林缓释胶囊的检测方法,包括如下步骤:
步骤S1,取一份标准规格的盐酸环苯扎林缓释胶囊,精密称量其质量,记为ma,其单位为mg;
步骤S2,把质量为ma的盐酸环苯扎林缓释胶囊溶解在甲醇溶剂中,得到混合溶液;
步骤S3,制备固相萃取膜,具体方法如下:利用离子缔合作用,磺酸钠化苯乙烯单体的阴离子基团与盐酸环苯扎林的阳离子基团自组装为烯基化离子对单体,在引发剂和交联剂作用下,烯基化离子对单体接枝聚合至烯基化多孔氧化铝膜的纳米孔中,洗脱掉盐酸环苯扎林,得到固相萃取膜;其中,固相萃取膜的萃取量>80µmol/g;
步骤S4,计算固相萃取膜的最小使用量mb-min,据此得到固相萃取膜的使用量mb>mb-min,具体过程如下:
mb-min=[(ma×wt%)/311.85]×103/80;
其中,wt%表示盐酸环苯扎林在盐酸环苯扎林缓释胶囊中的重量含量百分比;mb和mb-min的单位为g;
步骤S5,把质量为mb的固相萃取膜加入到步骤S2的混合溶液中,室温下振荡吸附,取出固相萃取膜,采用浓度1×10-3mol/L的NaOH溶液振荡解吸附,经氮气吹干之后利用流动相复溶至100μL,取5μL进样量,利用HPLC测定环苯扎林。
优选的,所述磺酸钠化苯乙烯单体包括:苯乙烯磺酸钠和/或六磺酸钠化苯乙烯单体M-Styrene-(SO3Na)6。
优选的,所述六磺酸钠化苯乙烯单体M-Styrene-(SO3Na)6的制备方法如下:
步骤S1,以对甲苯磺酸为催化剂,在催化作用下,4-乙烯基苯甲酸的羧基官能团与季戊四醇的羟基官能团发生酯化反应合成三羟基化苯乙烯单体M-Styrene-(OH)3;
步骤S2,在叔胺的催化作用下,氨基酸试剂的氨基官能团与苯乙烯磺酸钠的烯基官能团发生氮-烯迈克尔加成反应合成双磺酸钠化羧酸单体M-COOH-(SO3Na)2;
步骤S3,以对甲苯磺酸为催化剂,催化三羟基化苯乙烯单体M-Styrene-(OH)3的羟基官能团与双磺酸钠化羧酸单体M-COOH-(SO3Na)2的羧基官能团发生酯化反应,合成六磺酸钠化苯乙烯单体M-Styrene-(SO3Na)6。
优选的,所述叔胺催化剂选择使用1 5 7-三叠氮双环(4.4.0)癸-5-烯、7-甲基-1,5,7-三氮杂二环[4.4.0]癸-5-烯的一种或两种组合。
优选的,所述氨基酸试剂选择使用β-丙氨酸、γ-氨基丁酸、6-氨基己酸、12-氨基十二酸中的一种或以上组合。
优选的,所述流动相为乙腈和水,其体积比为2:3,水相中含10mM乙酸铵和0.1%甲酸。
优选的,所述固相萃取膜包括:固相萃取膜SPEM-(SO3)-Na+和/或固相萃取膜SPEM-[(SO3)-Na+]6。
优选的,所述固相萃取膜SPEM-(SO3)-Na+的萃取量为(80~130)µmol/g。
优选的,所述固相萃取膜SPEM-[(SO3)-Na+]6的萃取量为(420~480)µmol/g。
优选的,所述烯基化多孔氧化铝膜使用的多孔阳极氧化铝膜的孔直径200nm、孔径深度110µm。
与现有技术相比,本发明具备以下有益的技术效果:
本发明制备获得了两种固相萃取膜:固相萃取膜SPEM-(SO3)-Na+和固相萃取膜SPEM-[(SO3)-Na+]6;
通过萃取实验结果发现:固相萃取膜SPEM-(SO3)-Na+和固相萃取膜SPEM-[(SO3)-Na+]6都能够用于萃取盐酸环苯扎林缓释胶囊药品中的活性组分盐酸环苯扎林;
并且发现:固相萃取膜SPEM-[(SO3)-Na+]6对于盐酸环苯扎林的萃取能力显著优于固相萃取膜SPEM-(SO3)-Na+。
本发明提供了能够用于萃取盐酸环苯扎林缓释胶囊药品中活性组分盐酸环苯扎林的固相萃取膜SPEM-(SO3)-Na+和/或固相萃取膜SPEM-[(SO3)-Na+]6,并且提供了基于固相萃取膜SPEM-(SO3)-Na+和/或固相萃取膜SPEM-[(SO3)-Na+]6的固相萃取环苯扎林的可行方法。
附图说明
图1为烯基化离子对单体M-Styrene-[(SO3)-N+]的化学结构式;
图2为三羟基化苯乙烯单体M-Styrene-(OH)3的化学结构式;
图3为双磺酸钠化羧酸单体M-COOH-(SO3Na)2的化学结构式;
图4为六磺酸钠化苯乙烯单体M-Styrene-(SO3Na)6的化学结构式。
具体实施方式
实施例1-1:
制备烯基化多孔氧化铝(AAO)膜,其具体合成步骤如下:
步骤S1,首先把2mL乙烯基三乙氧基硅烷溶解在15mL无水乙醇中,之后加入1mL柠檬酸盐缓冲液(0.2mol/L、pH=6.4),配制得到混合溶液;
步骤S2,首先利用无水乙醇对多孔阳极氧化铝膜(精确称量质量记为mⅠ0、孔直径200nm、孔径深度110µm)活化处理2h,之后置于步骤S1配制的混合溶液中,并且抽真空处理2h,最后取出多孔阳极氧化铝膜、利用无水乙醇漂洗、于100℃下真空干燥1h,利用砂纸打磨多孔阳极氧化铝膜表面,利用无水乙醇漂洗,于40℃下真空干燥至恒重,得到烯基化多孔氧化铝(AAO)膜。
实施例1-2:
制备固相萃取膜SPEM-(SO3)-Na+,其制备机理:利用离子缔合作用,苯乙烯磺酸钠的阴离子基团[(SO3)-]与盐酸环苯扎林的阳离子基团[-N+H-(CH3)2]自组装为烯基化离子对单体M-Styrene-[(SO3)-N+](其化学结构式如图1所示),在引发剂和交联剂作用下,接枝聚合至烯基化多孔氧化铝(AAO)膜的纳米孔中,洗脱掉盐酸环苯扎林,得到固相萃取膜SPEM-(SO3)-Na+;
固相萃取膜SPEM-(SO3)-Na+的具体制备步骤如下:
步骤S1,把206mg(1mmoL)苯乙烯磺酸钠和312mg(1mmoL)盐酸环苯扎林溶解在30mL去离子水中,机械搅拌混合1h,在离子缔合作用下自组装为烯基化离子对单体M-Styrene-[(SO3)-N+];
步骤S2,向步骤S1中,加入3mL乙二醇二甲基丙烯酸酯交联剂、150mg2,2-偶氮二异丁腈AIBN引发剂,机械搅拌15min,加入烯基化多孔氧化铝(AAO)膜,通入氮气保护,于温度60℃下反应15h,取出多孔氧化铝膜AAO-[(SO3)-N+];
步骤S3,把步骤S2制备的多孔氧化铝膜AAO-[(SO3)-N+]放入浓度1×10-3mol/L的NaOH溶液中,振荡洗涤至检测不到盐酸环苯扎林为止,得到多孔氧化铝膜AAO-[(SO3)-];
步骤S4,把多孔氧化铝膜AAO-[(SO3)-]在40℃下真空干燥至恒重,得到固相萃取膜SPEM-(SO3)-Na+,精确称量其质量记为mⅠ。
实施例2-1:
制备三羟基化苯乙烯单体M-Styrene-(OH)3,其合成机理如下:以对甲苯磺酸为催化剂,在催化作用下,4-乙烯基苯甲酸的羧基官能团与季戊四醇的羟基官能团发生酯化脱水反应,合成得到三羟基化苯乙烯单体M-Styrene-(OH)3,其具体合成步骤如下:把148mg4-乙烯基苯甲酸溶解在20mLN,N-二甲基乙酰胺中,转移到配有分水器、冷凝管、温度计和磁力搅拌的烧瓶中,通入氮气保护,加入136mg季戊四醇、10mg对甲苯磺酸催化剂、10mL环己烷带水剂,在磁力搅拌、温度110℃下反应5h,停止加热与搅拌,冷却至室温,把反应产物与浓度5%的Na2CO3水溶液混合,超声混合后,采用去离子水洗涤,利用正己烷萃取,取上层清液用旋转蒸发仪除去溶剂,得到三羟基化苯乙烯单体M-Styrene-(OH)3,其化学结构式如图2所示;
三羟基化苯乙烯单体M-Styrene-(OH)3的核磁共振谱表征结果为:
1H NMR(400MHz,CDCl3),δ:1.83(s,3H,-OH),3.49(s,6H,-CH2-),4.11(s,2H,-CH2-),5.25(dd,1H,=CH2),5.76(dd,1H,=CH2),7.45(d,2H,Ar-H),7.67(d,2H,Ar-H),6.72(dd,1H,-CH=);
13C NMR(101MHz,CDCl3),δ:47.8(1C,>C<),61.4(1C,-CH2-),64.5(3C,-CH2-),114.3(1C,=CH2),136.1(1C,-CH=),125.7(2C,苯环碳),129.8(2C,苯环碳),129.3(1C,苯环碳),142.2(1C,苯环碳),165.9(1C,-COO-)。
实施例2-2:
制备双磺酸钠化羧酸单体M-COOH-(SO3Na)2,其合成机理如下:以叔胺为催化剂,在催化作用下,氨基酸试剂的氨基官能团与苯乙烯磺酸钠的烯基官能团发生氮-烯迈克尔加成反应合成得到双磺酸钠化羧酸单体M-COOH-(SO3Na)2;
其中,叔胺催化剂能够选择1 5 7-三叠氮双环(4.4.0)癸-5-烯、7-甲基-1,5,7-三氮杂二环[4.4.0]癸-5-烯的一种或两种组合;
氨基酸试剂能够选择β-丙氨酸、γ-氨基丁酸、6-氨基己酸、12-氨基十二酸中的一种或一种以上组合;
本实施例选择使用β-丙氨酸为氨基酸试剂,合成双磺酸钠化羧酸单体M-COOH-(SO3Na)2的具体步骤如下:在三口烧瓶中加入268mgβ-丙氨酸、1.24g苯乙烯磺酸钠、40mg1 57-三叠氮双环(4.4.0)癸-5-烯和20mg7-甲基-1,5,7-三氮杂二环[4.4.0]癸-5-烯,在温度60℃下机械搅拌反应12h,得到双磺酸钠化羧酸单体M-COOH-(SO3Na)2,其化学结构式如图3所示;
双磺酸钠化羧酸单体M-COOH-(SO3Na)2的核磁共振谱表征结果为:
1H NMR(400MHz,CDCl3),δ:2.47(t,2H,-CH2),2.67-2.69(m,8H,-CH2-),3.64(t,2H,-CH2-),7.55(d,4H,Ar-H),7.80(d,4H,Ar-H),11.0(s,1H,-OH);
13C NMR(101MHz,CDCl3),δ:33.4(2C,-CH2-),36.1(1C,-CH2-),52.8(1C,-CH2-),126.7(4C,苯环碳),129.0(4C,苯环碳),143.2(2C,苯环碳),147.0(2C,苯环碳),175.5(1C,-COOH)。
实施例2-3:
制备六磺酸钠化苯乙烯单体M-Styrene-(SO3Na)6,其合成机理如下:以对甲苯磺酸催化三羟基化苯乙烯单体M-Styrene-(OH)3的羟基官能团与双磺酸钠化羧酸单体M-COOH-(SO3Na)2的羧基官能团发生酯化反应,合成六磺酸钠化苯乙烯单体M-Styrene-(SO3Na)6,其具体合成步骤如下:在配有分水器、冷凝管、温度计和磁力搅拌的烧瓶中,加入50mLN,N-二甲基乙酰胺、1.2g双磺酸钠化羧酸单体M-COOH-(SO3Na)2、186mg三羟基化苯乙烯单体M-Styrene-(OH)3、1.4g对甲苯磺酸催化剂、15mL环己烷带水剂,通入氮气保护,在磁力搅拌、温度110℃下反应5h,停止加热与搅拌,冷却至室温,把反应产物与浓度5%的Na2CO3水溶液混合,超声混合后,采用去离子水洗涤,利用正己烷萃取,取上层清液用旋转蒸发仪除去溶剂,得到六磺酸钠化苯乙烯单体M-Styrene-(SO3Na)6,其化学结构式如图4所示;
六磺酸钠化苯乙烯单体M-Styrene-(SO3Na)6的核磁共振谱表征结果为:
1H NMR(400MHz,CDCl3),δ:2.49(t,6H,-CH2-),2.67-2.69(m,24H,-CH2-),3.76(t,6H,-CH2-),4.11(s,2H,-CH2-),5.25(dd,1H,=CH2),5.76(dd,1H,=CH2),7.45(d,2H,Ar-H),7.55(d,12H,Ar-H),7.67(d,2H,Ar-H),7.80(d,12H,Ar-H),6.72(dd,1H,-CH=);
13C NMR(101MHz,CDCl3),δ:32.3(3C,-CH2-),33.4(6C,-CH2-),37.9(1C,-C-),53.1(3C,-CH2-),60.7(6C,-CH2-),62.0(1C,-CH2-),62.4(3C,-CH2-),114.3(1C,=CH2),125.7(2C,苯环碳),126.7(12C,苯环碳),129.0(12C,苯环碳),129.3(1C,苯环碳),129.8(2C,苯环碳),136.1(1C,-CH=),142.2(1C,苯环碳),143.2(6C,苯环碳),147.0(6C,苯环碳),165.9(1C,-COO-),171.0(3C,-COO-)。
实施例2-4:
制备固相萃取膜SPEM-[(SO3)-Na+]6,按照实施例1-2中固相萃取膜SPEM-(SO3)-Na+的制备方法,并且使用1.715g(1mmoL)六磺酸钠化苯乙烯单体M-Styrene-(SO3Na)6替换206mg(1mmoL)苯乙烯磺酸钠、使用1.872g(6mmoL)盐酸环苯扎林替换312mg(1mmoL)盐酸环苯扎林,制备得到固相萃取膜SPEM-[(SO3)-Na+]6,精确称量其质量记为mⅡ;
其中,固相萃取膜SPEM-[(SO3)-Na+]6使用的多孔阳极氧化铝膜为质量记为mⅡ0。
实施例3-1:
为了考察固相萃取膜SPEM-(SO3)-Na+和SPEM-[(SO3)-Na+]6对于盐酸环苯扎林的萃取性能,设置如下的萃取实验,其具体实验方法如下:
步骤S1,精密称量纯度98%的盐酸环苯扎林溶解在甲醇溶剂中,在定量瓶内定容,逐级稀释,定量配制得到盐酸环苯扎林标准溶液CHSS-Ⅰ和盐酸环苯扎林标准溶液Ⅱ,所述两份标准溶液的体积都为100mL、浓度都为10µmol/L;
步骤S2,把质量为mⅠ的固相萃取膜SPEM-(SO3)-Na+放入步骤S1配制的盐酸环苯扎林标准溶液CHSS-Ⅰ(100mL、10µmol/L)中,室温下以200r/min转速振荡吸附1h,取出萃取膜,利用HPLC测定剩余溶液的浓度CⅠe,按照下式计算固相萃取膜SPEM-(SO3)-Na+的萃取量EC[SPEM-(SO3)-Na+],其具体计算过程如下:
EC[SPEM-(SO3)-Na+](µmol/g)=[(10µmol/L-CⅠe(µmol/L))×100mL×10-3]/(mⅠ-mⅠ0)(g);
步骤S3,把质量为mⅡ的固相萃取膜SPEM-[(SO3)-Na+]6放入步骤S1配制的盐酸环苯扎林标准溶液CHSS-Ⅱ(100mL、10µmol/L)中,室温下以200r/min转速振荡吸附1h,取出萃取膜,利用HPLC测定剩余溶液的浓度CⅡe,按照下式计算固相萃取膜SPEM-[(SO3)-Na+]6的萃取量EC[SPEM-[(SO3)-Na+]6],其具体计算过程如下:
EC[SPEM-[(SO3)-Na+]6](µmol/g)=[(10µmol/L-CⅡe(µmol/L))×100mL×10-3]/(mⅡ-mⅡ0)(g);
其中,HPLC的测定条件如下:使用岛津UFLC超高效液相色谱仪,色谱柱为UltimateXB-CN(5μm,2.1*150mm);流动相为乙腈:水(含10mM乙酸铵和0.1%甲酸)=2:3(体积比);流速:0.35ml/min;进样量:5μL;柱温:35℃;
上述测试结果如下表1所示;
表1 固相萃取膜SPEM-(SO3)-Na+和SPEM-[(SO3)-Na+]6对于盐酸环苯扎林的萃取实验结果
固相萃取膜编号 | 萃取量EC(µmol/g) |
SPEM-(SO3)-Na+ | 122 |
SPEM-[(SO3)-Na+]6 | 465 |
由表1萃取实验数据可知:固相萃取膜SPEM-(SO3)-Na+和固相萃取膜SPEM-[(SO3)-Na+]6都能够用于萃取盐酸环苯扎林,并且固相萃取膜SPEM-[(SO3)-Na+]6对于盐酸环苯扎林的萃取能力显著优于固相萃取膜SPEM-(SO3)-Na+。
实施例3-2:
盐酸环苯扎林缓释胶囊的检测方法,其具体步骤如下:取1粒(15mg/粒)盐酸环苯扎林缓释胶囊溶解在甲醇溶剂中,加入1g固相萃取膜SPEM-[(SO3)-Na+]6,室温下以200r/min转速振荡吸附1h,取出萃取膜,放入浓度1×10-3mol/L的NaOH溶液中,振荡解吸附1h,经氮气吹干之后利用流动相(流动相为乙腈:水(含10mM乙酸铵和0.1%甲酸)=2:3(体积比))复溶至100μL,取5μL进样量,利用HPLC测定环苯扎林,其测定条件如下:使用岛津UFLC超高效液相色谱仪,色谱柱为Ultimate XB-CN(5μm,2.1*150mm);流动相为乙腈:水(含10mM乙酸铵和0.1%甲酸)=2:3(体积比);流速:0.35ml/min;柱温:35℃。
Claims (6)
1.一种盐酸环苯扎林缓释胶囊的检测方法,其特征在于,包括如下步骤:
步骤S1-1,取一份标准规格的盐酸环苯扎林缓释胶囊,精密称量其质量,记为ma,其单位为mg;
步骤S1-2,把质量为ma的盐酸环苯扎林缓释胶囊溶解在甲醇溶剂中,得到混合溶液;
步骤S1-3,制备固相萃取膜,具体方法如下:利用离子缔合作用,磺酸钠化苯乙烯单体的阴离子基团与盐酸环苯扎林的阳离子基团自组装为烯基化离子对单体,在引发剂和交联剂作用下,烯基化离子对单体接枝聚合至烯基化多孔氧化铝膜的纳米孔中,洗脱掉盐酸环苯扎林,得到固相萃取膜;其中,固相萃取膜的萃取量>80µmol/g;
步骤S1-4,计算固相萃取膜的最小使用量mb-min,据此得到固相萃取膜的使用量mb>mb-min,具体过程如下:
mb-min=[(ma×wt%)/311.85]×103/80;
其中,wt%表示盐酸环苯扎林在盐酸环苯扎林缓释胶囊中的重量含量百分比;mb和mb-min的单位为g;
步骤S1-5,把质量为mb的固相萃取膜加入到步骤S2的混合溶液中,室温下振荡吸附,取出固相萃取膜,采用浓度1×10-3mol/L的NaOH溶液振荡解吸附,经氮气吹干之后利用流动相复溶至100μL,取5μL进样量,利用HPLC测定环苯扎林;
所述磺酸钠化苯乙烯单体包括:苯乙烯磺酸钠和/或六磺酸钠化苯乙烯单体M-Styrene-(SO3Na)6;
所述六磺酸钠化苯乙烯单体M-Styrene-(SO3Na)6的制备方法如下:
步骤S2-1,以对甲苯磺酸为催化剂,在催化作用下,4-乙烯基苯甲酸的羧基官能团与季戊四醇的羟基官能团发生酯化反应合成三羟基化苯乙烯单体M-Styrene-(OH)3;
步骤S2-2,在叔胺的催化作用下,氨基酸试剂的氨基官能团与苯乙烯磺酸钠的烯基官能团发生氮-烯迈克尔加成反应合成双磺酸钠化羧酸单体M-COOH-(SO3Na)2;
步骤S2-3,以对甲苯磺酸为催化剂,催化三羟基化苯乙烯单体M-Styrene-(OH)3的羟基官能团与双磺酸钠化羧酸单体M-COOH-(SO3Na)2的羧基官能团发生酯化反应,合成六磺酸钠化苯乙烯单体M-Styrene-(SO3Na)6;
所述流动相为乙腈和水,其体积比为2:3,水相中含10mM乙酸铵和0.1%甲酸;
所述固相萃取膜包括:固相萃取膜SPEM-(SO3)-Na+和/或固相萃取膜SPEM-[(SO3)-Na+]6;
所述HPLC的色谱柱为Ultimate XB-CN。
2.根据权利要求1所述的一种盐酸环苯扎林缓释胶囊的检测方法,其特征在于,所述步骤S2-2:叔胺催化剂选择使用1 5 7-三叠氮双环(4.4.0)癸-5-烯、7-甲基-1,5,7-三氮杂二环[4.4.0]癸-5-烯的一种或两种组合。
3.根据权利要求1所述的一种盐酸环苯扎林缓释胶囊的检测方法,其特征在于,所述步骤S2-2:氨基酸试剂选择使用β-丙氨酸、γ-氨基丁酸、6-氨基己酸、12-氨基十二酸中的一种或以上组合。
4.根据权利要求1所述的一种盐酸环苯扎林缓释胶囊的检测方法,其特征在于,所述固相萃取膜SPEM-(SO3)-Na+的萃取量为(80~130)µmol/g。
5.根据权利要求1所述的一种盐酸环苯扎林缓释胶囊的检测方法,其特征在于,所述固相萃取膜SPEM-[(SO3)-Na+]6的萃取量为(420~480)µmol/g。
6.根据权利要求1所述的一种盐酸环苯扎林缓释胶囊的检测方法,其特征在于,所述烯基化多孔氧化铝膜使用的多孔阳极氧化铝膜的孔直径200nm、孔径深度110µm。
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Citations (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
HU0104339D0 (en) * | 2000-10-17 | 2001-12-28 | Warner Lambert Co | Method of treating cartilage damage |
WO2002026867A2 (en) * | 2000-09-29 | 2002-04-04 | The Regents Of The University Of California | Dendrimeric support or carrier macromolecule |
CN111707764A (zh) * | 2020-06-30 | 2020-09-25 | 正大制药(青岛)有限公司 | 一种盐酸环苯扎林缓释胶囊的检测方法 |
CN114563369A (zh) * | 2022-03-08 | 2022-05-31 | 正大制药(青岛)有限公司 | 一种用于盐酸环苯扎林缓释胶囊的质量检测方法 |
CN114674945A (zh) * | 2022-03-08 | 2022-06-28 | 正大制药(青岛)有限公司 | 一种用于盐酸环苯扎林的质量检测方法 |
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Patent Citations (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2002026867A2 (en) * | 2000-09-29 | 2002-04-04 | The Regents Of The University Of California | Dendrimeric support or carrier macromolecule |
HU0104339D0 (en) * | 2000-10-17 | 2001-12-28 | Warner Lambert Co | Method of treating cartilage damage |
CN111707764A (zh) * | 2020-06-30 | 2020-09-25 | 正大制药(青岛)有限公司 | 一种盐酸环苯扎林缓释胶囊的检测方法 |
CN114563369A (zh) * | 2022-03-08 | 2022-05-31 | 正大制药(青岛)有限公司 | 一种用于盐酸环苯扎林缓释胶囊的质量检测方法 |
CN114674945A (zh) * | 2022-03-08 | 2022-06-28 | 正大制药(青岛)有限公司 | 一种用于盐酸环苯扎林的质量检测方法 |
Non-Patent Citations (3)
Title |
---|
A New Methodology to Create Polymeric Nanocarriers Containing Hydrophilic Low Molecular-Weight Drugs: A Green Strategy Providing a Very High Drug Loading;María Gabriela Villamizar-Sarmiento;Mol. Pharmaceutics;1-10 * |
HPLC-MS/MS 测定人血浆中环苯扎林浓度及药动学研究;钱振宇;2010年中国药学大会暨第十届中国药师周论文集;3606-3613 * |
The key role of the drug self-aggregation ability to obtain optimal nanocarriers based on aromatic-aromatic drug-polymer interactions;María Gabriela Villamizar-Sarmiento等;European Journal of Pharmaceutics and Biopharmaceutics;19-29 * |
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