二水盐酸纳洛酮欧洲药典检测方法原创翻译

Naloxone hydrochloride dihydrate

EUROPEAN PHARMACOPOEIA 8.0

TESTS

04/2013:072Absorbance . Dissolve 1.50g in methylene chloride R and 9

dilute to 50.0mL with the same solvent. The absorbance (2.2.25) measured at 420nm is not greater than 0.10. 二水盐酸纳洛酮

Related substances . Examine by thin-layer chromatography (2.2.27), using a TLC silica gel F 254plate R .

Test solution (a). Dissolve 0.20g of the substance to be examined in methylene chloride R and dilute to 10mL with

the same solvent.

Test C 19H 22ClNO 4,2H 2O M r 399.9

20mL solution with methylene (b). Dilute chloride 1mL of R test .

solution (a)to [51481-60-8]

Reference solution (a). Dissolve 20mg of nalidixic acid CRS in methylene chloride R and dilute to 20mL with the same

定义

solvent.

4,5α-Epoxy-3,14-dihydroxy-17-(prop-2-enyl)morphinan-6-one hydrochloride dihydrate. Reference solution (b). Dilute 2mL of test solution (b)to 含量:98.0%to 102.0%(无水物). 10mL with methylene chloride R .

性状

Reference 外观:吸湿性的白色结晶或结晶性粉末，

(b)to 10mL solution with methylene (c). Dilute chloride 1mL of R reference .

solution 溶解度; 易溶于水，可溶于乙醇（96％），在甲苯中几乎不溶

Reference 鉴定

(b)to 25mL solution with methylene (d). Dilute chloride 1mL of R reference .

solution 第一识别：A, C. Apply to the plate 10μLof each solution. Develop over a path of 第二识别:B, C.

15cm using a mixture of 10volumes of dilute ammonia R1, 20A 红外吸收分光光度法（2.2.24）。volumes of methylene chloride R and 70volumes of alcohol R . 对比：盐酸纳洛酮二水CRS 。Allow the plate to dry in air and examine in

ultraviolet light at 254nm. Any spot in the chromatogram

B. 薄层色谱法（2.2.27）。

obtained with the test solution (a),apart from the principal spot, 测试方法将8毫克物质溶解在0.5毫升水中并稀释至1毫升is not more intense than the spot in the chromatogram obtained 甲醇中检测. 参考方法：将8毫克二水盐酸纳洛酮溶解在0.5with reference solution (c)(0.1per cent) and not more than one 毫升水中并加1毫升甲醇稀释. such spot is more intense than the spot in the chromatogram 板块：薄层色谱硅胶板

obtained with reference solution (d).

流动相：通过60毫升稀释的溶液氨R2与100毫升丁醇R 的Heavy metals (2.4.8). 1.0g complies with test D for heavy

混合物，混合出5单位体积甲醇R 和95单位体积的上层溶metals (20液

standard ppm). solution Prepare (10the ppm reference Pb) R solution using 2mL of lead .

应用：5μL。

Loss on drying (2.2.32). Not more than 0.5per cent, 发展：在板块的2/3。干燥：在空气中。

determined on 1.000g by drying in an oven at 105°C.

检测：用在氯化铁溶液，R1铁氰化钾R A 新鲜制备的5g /L Sulfated ash (的溶液喷雾; 日光中检查。

1.02.4.14). Not more than 0.1per cent, determined on g.

结果：用测试溶液中获得的色谱图的主要点是在适当的位置，颜色和大小，以在与参考溶液的色谱图中的主要点类似。

ASSAY

C. 氯化物反应（2.3.1）Dissolve 0.150g in 10mL of methylene chloride R and add 30mL of 测试

2-propanol R and 10mL of carbon dioxide-free water R . Keep the titration vessel covered and pass nitrogen R

溶液S:溶解0.5G 在无水二氧化碳中并稀释至25毫升到相同through 溶剂。

temperature the M ethanolic sodium of solution the solution throughout hydroxide between , determining 15the °Cand titration. the

20°C.Keep Titrate the

with 0.1溶液外观。溶液清澄（2.2.1）和无色（2.2.2，方法二）。end-point potentiometrically (2.2.20) using a silver-silver

chloride comparison electrode with a sleeve diaphragm or a

酸度或碱度。在10毫升的溶液中添加0.05毫升甲基红溶capillary tip, filled with a saturated solution of lithium chloride R in ethanol R 液。不超过0.2毫升的0.02M 氢氧化钠或0.02M 盐酸能, and a glass electrode as indicator

electrode.

改变指示剂的颜色。

1mL of 0.1M ethanolic sodium hydroxide is 比旋光度（2.2.7）：-181〜-170（无水物），由溶液来确equivalent to 23.22mg of C 12H 12N 2O 3.

定

STORAGE

Store in an airtight container, protected from light.

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See the information section on general monographs (coverpages)

EUROPEAN PHARMACOPOEIA 8.0

Naloxone hydrochloride dihydrate

杂质D. 液相色谱法（2.2.29）。

流动相：

方法A. 将1.58克碳酸氢铵溶解在950毫升水中，调节至pH 9.0，用浓氨水加水稀释至1000毫升

-流动相A ：乙腈R ，四氢呋喃R ，溶液A （2：4：94V/V/V ）;

-流动相B ：四氢呋喃R ，乙腈R ，溶液A （4:17:79V /V /测试溶液将0.5克被测试物质溶解在10.3克/升的盐酸溶V ）;

液，稀释到20.0毫升的相同溶液。

对照溶液（a ）将10.0毫克纳洛酮杂质D 溶解到10.3克/升时间流动相A 流动相B 盐酸溶液并稀释至20.0毫升的相同溶液中。将5.0毫升的该(分钟) (percent V/V)

(percent V/V)

溶液稀释成10.3克/升的100.0毫升的盐酸溶液

0-40100→0

0→100

参考溶液（b ）稀释5.0毫升的对照溶液（a ）至100毫升40-50

100

10.3克/升的盐酸溶液

流量:1.5mL/min.

参考溶液（c ）4毫升试验溶液中加2.0毫升对照溶液（a ）检测：分光光度计230纳米。和稀释至10.3克/升的20毫升盐酸溶液注射:20μL.

Column :

参照纳洛酮相对保留数据（保留时间=约11分钟）：杂质C =约0.6; 杂质A=约0.8; 杂质F =0.9左右; 杂质D =约1.1; 杂–尺寸:l =0.25m, Ø=4.6mm ;

质E =约3.0; 杂质B =约3.2。

–固定相：封端的十八烷基硅烷键色谱（5微米）硅胶; 杂质鉴定：根据杂质的A ，B ，C ，D ，E 和F

–温度:40°C.使用纳洛酮峰鉴定和参照溶液提供的色谱图，以鉴定该峰流动相：

-流动相A ：乙腈R1，溶液A （20:80V /V ）; 系统适用：参照溶液

-流动相B ：乙腈，R1，溶液A （40:60V /V ）;

峰谷比：最小2.0，其中的Hp=高度的峰谷以上（杂质D 原因），HV=高度曲线在该峰峰值（纳洛酮分离的最低点的基线）以上时间流动相A

流动相B

限制：

(分钟) (percent V/V)(percent V/V)-修正系数：内容计算，以0.5乘杂质E 的峰面积;

-杂质A ，B ，C ，E ，F ：对于每个杂质，不超过参照溶液50-51100→00→100（0.2％）的色谱图的主要峰面积;

51-60

100

-未指定的杂质：对于每个杂质，参考溶液（b ）（0.10％）的色谱图的主要峰面积不超过0.5倍;

流量：2.0毫升/分钟。-总共：参照溶液（0.8％）色谱图的主要峰面积不超过4倍; -无视限制：为参考溶液（0.05％）的色谱图峰面积的0.25检测：分光光度计210纳米。

倍。

水（2.5.12）：7.5％至11.0％以0.200克来鉴定。

注射：10μL的测试溶液和参比溶液（b ）和（c ）。硫酸盐灰分（2.4.14）：0.2%的最大值，以0.50克来鉴定。含量

参照纳洛酮相对保留（保留时间=约50分钟）：杂质D =约溶解0.300克至50毫升乙醇（96％）中并添加5.0毫升的0.8。

0.01M 盐酸。取0.1M 氢氧化钠乙醇钠, 实施电位滴定法。系统适用性：参考解决方案（三）：

（2.2.20）。读出2点拐点之间加入的体积。1毫升0.1M 的乙醇氢氧化钠相当于36.38毫克C19H22ClNO4。-对称因子：由于杂质D 原因，最大峰值为1.8

存储

密封容器，避光限制：

-杂质D ：在与参考溶液（b ）（75ppm ）中获得的色谱图中杂质

主峰面积不超过1.5倍。

特定杂质:A, B, C, D, E, F.

相关物质液相色谱法（2.2.29）。

其他可检测的杂质（以下物质，如果水平充分存在，可以通过论述里某个或另一个测试来检测，它们受限于针对其他/未溶液A. 将1.10克钠辛烷溶解于950毫升水中，，用50%体指定的杂质的普遍接受标准和/或适于药物使用的一般性专著积比的磷酸调节至pH 2.0，过滤用水稀释至1000毫升.

内容。因此，没有必要鉴别这些杂质作适用示范。参见测试溶液将被测试物质溶解在10.3克/升的盐酸溶液中，并5.10。控制用于药物用途的物质杂质）：G 。

稀释成25毫升相等溶液

参考溶液（a ）将5毫克纳洛酮溶解到1毫升的10.3克/升盐酸溶液中，作为峰值鉴别（含有杂质A ，B ，C ，D ，E 和F ）

参考溶液（b ）将1毫升的测试溶液和10.3克/升盐酸溶液稀释为20.0毫升。将1毫升的该溶液与10.3克/升的盐酸溶液稀释为25毫升列项：

-尺寸：L=0.125M，Ø=4.0MM;

-固定相：封端辛基甲硅烷基色谱（5微米）硅胶; -温度：40℃。

2821

Naltrexone hydrochloride

EUROPEAN PHARMACOPOEIA 8.0

01/2008:1790

NALTREXONE HYDROCHLORIDE

Naltrexoni hydrochloridum

A. 4,5α-epoxy-3,14-dihydroxymorphinan-6-one

(noroxymorphone),

C 20H 24ClNO 4M r 377.9

DEFINITION

17-(Cyclopropylmethyl)-4,5α-epoxy-3,14-dihydroxy-B. 4,5α-epoxy-14-hydroxy-17-(prop-2-enyl)-3-(prop-2-morphinan-6-one hydrochloride. It may be anhydrous, a enyloxy)morphinan-6-one (3-O -allylnaloxone),

monohydrate or a dihydrate, a mixture or a solvate.

Content :98.0per cent to 102.0per cent (anhydroussubstance).

CHARACTERS

Appearance :white or almost white powder, very hygroscopic. Solubility :freely soluble in water, slightly soluble in ethanol (96per cent), practically insoluble in methylene chloride.

IDENTIFICATION

C. 4,5α-epoxy-3,10α,14-trihydroxy-17-(prop-2-A. Infrared absorption spectrophotometry (2.2.24).

enyl)morphinan-6-one (10α-hydroxynaloxone),

Dissolve 20mg in water R and dilute to 5mL with the same solvent. Make alkaline with dilute ammonia R1. Shake with 10mL of methylene chloride R , separate the organic

layer Comparison obtained and :in evaporate naltrexone vacuo .

the solvent. Dry the residue hydrochloride CRS . B. It gives reaction (a)of chlorides (2.3.1).

TESTS

D. 7,8-didehydro-4,5α-epoxy-3,14-dihydroxy-17-(prop-2-Solution S . Dissolve 0.40g in carbon dioxide-free water R enyl)morphinan-6-one (7,8-didehydronaloxone),

and dilute to 20.0mL with the same solvent.

Appearance more (2.2.2, intensely of Method coloured solution II ).

than . Solution reference S is solution clear (2.2.1Y ) and not

6or B 6

Acidity and alkalinity . To 10mL of solution S, add 0.05mL of methyl

red solution R . Not more than 0.2mL of 0.02M sodium hydroxide or 0.02M hydrochloric acid is required to

change Specific the colour of the indicator.

E. 4,5α:4′,5′α-diepoxy-3,3′,14,14′-tetrahydroxy-17,17′-bis(prop-2-enyl)-2,2′-bimorphinanyl-6,6′-(anhydrousoptical substance).

rotation (2.2.7) :−187to −195dione (2,2′-binaloxone),

Dissolve 0.40g in water R and dilute to 20.0mL with the same solvent.

Related substances . Liquid chromatography (2.2.29).

Test solution . Dissolve 20.0mg of the substance to be examined in 0.1M hydrochloric acid and dilute to 10.0mL

with Reference the solution same solvent.

(a). Dissolve 5.0mg of naltrexone impurity C CRS in 0.1M hydrochloric acid and dilute to

F. 4,5α-epoxy-3,10β,14-trihydroxy-17-(prop-2-2.5Reference mL with solution the (b)same solvent.

. Dilute 1.0mL of the test solution

enyl)morphinan-6-one (10β-hydroxynaloxone),

and M hydrochloric 1.0mL of reference acid . Dilute solution 1.0mL (a)of to this 100.0solution mL with to 10.00.1mL Column with 0.1M hydrochloric acid .

size l :

–:=0.15m, Ø=4.6mm ;

–stationary phase :octadecylsilyl silica gel for chromatography R1(5μm);

–G. 4,5α-epoxy-14-hydroxy-3-methoxy-17-(prop-2-

Mobile temperature phase :40°C.:

enyl)morphinan-6-one (3-O -methylnaloxone).

–mobile phase A :1.1g/Lsolution of sodium octanesulfonate R adjusted to

pH 2.3with phosphoric acid R ;

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