loading布洛芬片 BP2010 加速试验检验方法
一、 鉴别
A片剂碾碎成粉后，取0.5g溶于20ml的丙酮中，过滤，流动空气脱水滤液（不要加热），收集残留物。残留物的红外吸收图谱要与标准品吸收图谱一致（Appendix II A；RS-186） B石油醚重结晶后（沸点范围40°到60°）A中残留物的熔点约为75摄氏度（Appendix V A.）。
二、 相关物质
按照液相色谱方法（Appendix III D），使用以下溶液：
溶液1 ：取已碾成粉的布洛芬片0.2g，加30ml甲醇，振荡30分钟，再加入30ml甲醇后，用水定容到100ml，混匀，利用玻璃微孔滤纸（glass microfibre filter paper）过滤。推荐Whatman GF/C这个型号的产品。
溶液2：把溶液1用流动相介质稀释100倍
溶液3：用甲醇配置0.006%w/v的布洛芬杂质B标准品（欧洲标准）（可以使用1体积的杂质B欧洲标准品稀释到10体积来配置），使用2.5ml该溶液溶解50mg布洛芬英国药典标准品，甲醇定容到25ml。 色谱条件
A 使用不锈钢色谱柱（15 cm × 4.6 mm），利用色谱级球形封端十八烷基硅烷键合硅胶（5μm），
推荐使用Spherisorb ODS 2柱子。
B使用无梯度洗脱和下文所述的流动相 C流速为2ml/min D 常温柱温
E检测波长为214nm F上样量为20μl
G在开始检测前先通45分钟流动相以稳定柱子
H保持总保留时间是主峰位置的1.5倍；如果按照前述条件设置色谱环境，布洛芬的保留时间大约是20分钟。 流动相
0.5体积的正磷酸，340体积的乙腈，600体积水，混匀平衡后，用水稀释到总共1000体积。 系统适应性
使用溶液3得到的色谱峰，测量峰高a：由2-(4-butylphenyl)-propionic acid产生的峰2 - （4 -
苯基）丙酸和峰高b：由布洛芬产生的峰；这两个峰的曲线最低点必须可以分离。本实验不允许峰a大于1.5倍的峰b。如果有必要的话，可以通过调整乙腈的浓度来得到满足需要的溶液。
限制：
1由溶液1得到的色谱图：所有通过布洛芬杂质B得到的色谱图必须小于溶液3得到的色谱图。（0.3%） 2由溶液2得到的色谱图：每一个次高的色谱峰面积必须小于主峰面积的0.3倍。（0.3%）
3由溶液2得到的色谱图：所有次高的色谱峰面积的和，不包括杂质B产生的峰，必须小于主峰面积的0.7倍。（0.7%）
由溶液2得到的色谱图，忽略任何峰面积小于0.1倍的主峰的峰。（0.1%）
三、 含量检测
称重20片，使用液相色谱法Appendix III D，使用下列溶液：
1 0.2g的布洛芬使用30ml的布洛芬振荡溶解30分钟，加流动相溶液到100ml混匀。离心25ml溶液，转速为2500 g，5分钟，使用上清液。 2使用0.2%w/v 的布洛芬英国标准品 色谱条件
A 使用不锈钢色谱柱（25 cm × 4.6 mm），利用色谱级球形封端十八烷基硅烷键合硅胶（10μm），
推荐使用Nucleosil C18柱子。
B使用无梯度洗脱和下文所述的流动相 C流速为1.5ml/min D 常温柱温
E检测波长为264nm F上样量为20μl 流动相
3体积的正磷酸，247体积的水，750体积的甲醇
按照C13H18O2 计算布洛芬的含量，在95%-105%的含量为正常。 A. Extract a quantity of the powdered tablets containing 0.5 g of Ibuprofen with 20 ml of acetone , filter and evaporate the filtrate to dryness in a current of air without heating. The infrared absorption spectrum of the residue, Appendix II A, is concordant with the reference spectrum of ibuprofen (RS 186) . B. Melting point of the residue obtained in test A, after recrystallisation from petroleum spirit (boiling range, 40° to 60°), about 75°, Appendix V A. Related substances Carry out the method for liquid chromatography , Appendix III D, using the following solutions. (1) Add 30 ml of methanol to a quantity of the powdered tablets containing 0.2 g of Ibuprofen, shake for 30 minutes, add 30 ml of methanol and sufficient water to produce 100 ml, mix and filter through a glass microfibre filter paper (Whatman GF/C is suitable). (2) Dilute 1 volume of solution (1) to 100 volumes with the mobile phase. (3) Dissolve 50 mg of ibuprofen BPCRS in 2.5 ml of a 0.006% w/v solution of Ibuprofen Impurity B EPCRS in methanol (prepared by diluting 1 volume of Ibuprofen Impurity B EPCRS to 10 volumes with methanol ) and add sufficient methanol to produce 25 ml. CHROMATOGRAPHIC CONDITIONS
(a) Use a stainless steel column (15 cm × 4.6 mm) packed with end-capped octadecylsilyl silica gel for chromatography (5 μm) (Spherisorb ODS 2 is suitable). (b) Use isocratic elution and the mobile phase described below. (c) Use a flow rate of 2 ml per minute. (d) Use an ambient column temperature. (e) Use a detection wavelength of 214 nm. (f) Inject 20 μl of each solution.
(g) Equilibrate the column with the mobile phase for about 45 minutes before starting the chromatography.
(h) Allow the chromatography to proceed for 1.5 times the retention time of the principal peak. When the chromatograms are recorded under the conditions described above, the retention time of ibuprofen is about 20 minutes.
MOBILE PHASE
0.5 volume of orthophosphoric acid , 340 volumes of acetonitrile and 600 volumes of water diluted to 1000 volumes with water after equilibration.
SYSTEM SUITABILITY
In the chromatogram obtained with solution (3) measure the height (a) of the peak due to
2-(4-butylphenyl)-propionic acid and the height (b) of the lowest point of the curve separating this peak from that due to ibuprofen. The test is not valid unless a is greater than 1.5b. If necessary, adjust the concentration of acetonitrile in the mobile phase to obtain the required resolution.
LIMITS
In the chromatogram obtained with solution (1):
the area of any peak corresponding to ibuprofen impurity B is not greater than the area of the corresponding peak in the chromatogram obtained with solution (3) (0.3%);
the area of any other secondary peak is not greater than 0.3 times the area of the principal peak in the chromatogram obtained with solution (2) (0.3%);
the sum of the area of any secondary peaks , other than the peak due to impurity B, is not greater than 0.7 times the area of the principal peak in the chromatogram obtained with solution (2) (0.7%). Disregard any peak the area of which is less than 0.1 times the area of the principal peak in the chromatogram obtained with solution (2) (0.1%).
Weigh and powder 20 tablets. Carry out the method for liquid chromatography , Appendix III D, using the following solutions.
(1) Shake a quantity of the powdered tablets containing 0.2 g of Ibuprofen with 30 ml of the mobile phase for 30 minutes, add sufficient of the mobile phase to produce 100 ml and mix thoroughly. Centrifuge 25 ml of the solution at 2500 g for 5 minutes and use the supernatant liquid. (2) 0.2% w/v of ibuprofen BPCRS in the mobile phase.
CHROMATOGRAPHIC CONDITIONS
(a) Use a stainless steel column (25 cm × 4.6 mm) packed with end-capped octadecylsilyl silica gel for chromatography (10 μm) (Nucleosil C18 is suitable). (b) Use isocratic elution and the mobile phase described below. (c) Use a flow rate of 1.5 ml per minute. (d) Use an ambient column temperature. (e) Use a detection wavelength of 264 nm. (f) Inject 20 μl of each solution.
MOBILE PHASE
3 volumes of orthophosphoric acid , 247 volumes of water and 750 volumes of methanol.
DETERMINATION OF CONTENT
Calculate the content of C13H18O2 using the declared content of C13H18O2 in ibuprofen BPCRS . Content of ibuprofen, C13H18O2 95.0 to 105.0% of the stated amount.