【摘要】 目的:考察注射用丹参多酚酸与8种临床常用溶剂的配伍稳定性。方法:参照药品说明书,取注射用丹参多酚酸适量,分别与0.9%氯化钠注射液、5%葡萄糖注射液、10%葡萄糖注射液、复方氯化钠注射液、甘露醇注射液、甘油果糖氯化钠注射液、乳酸钠林格注射液、葡萄糖氯化钠注射液各250 m L配伍。在室温避光条件下,分别于配伍后0、1、2、4、8 h观察各配伍液的外观,检测其p H、不溶性微粒数、最大吸收波长和最大吸收度,并采用高效液相色谱法测定各配伍液中丹酚酸B、迷迭香酸、紫草酸和丹酚酸Y的含量。结果:在上述条件下,各配伍液在8 h内外观和p H均无明显变化,最大吸收波长为284.5~286.0 nm。与甘露醇注射液配伍后,配伍液中粒径≥10μm的微粒数(配伍后1~8 h)和≥25μm的微粒数(配伍后4~8 h)均超出2015年版《中国药典》规定范围,最大吸收度变化明显(RSD=9.17%,n=5),且丹酚酸B、迷迭香酸、紫草酸和丹酚酸Y相对百分含量的降幅均超过了10%(RSD分别为14.65%、6.45%、8.97%、12.49%,n=5);与乳酸钠林格注射液配伍后,配伍液中迷迭香酸和紫草酸的相对百分含量变化较大(RSD分别为14.57%、7.28%,n=5);与5%葡萄糖注射液配伍后4~8 h、与甘油果糖氯化钠注射液配伍后8 h,配伍液中迷迭香酸的相对百分含量均低于90%(RSD分别为6.30%、4.86%,n=5);与甘油果糖氯化钠注射液配伍后0 h,配伍液中粒径≥25μm的微粒数超出药典标准;其他配伍液中不溶性微粒数均符合药典标准,最大吸收度变化不大(RSD<5%,n=5),且各待测物相对百分含量的变化均未超过10%。结论:临床应避免注射用丹参多酚酸与甘露醇注射液、乳酸钠林格注射液和甘油果糖氯化钠注射液配伍使用;与5%葡萄糖注射液配伍后应在4 h内使用;可与0.9%氯化钠注射液、10%葡萄糖注射液、复方氯化钠注射液、葡萄糖氯化钠注射液配伍使用。更多还原

【Abstract】 OBJECTIVE:To investigate the compatibility stability of Salvianolic acid for injection(SAFI) combined with 8kinds of common solvents. METHODS:Referring to package inserts,SAFI was collected and combined with 0.9% Sodium chloride injection,5% Glucose injection,10% Glucose injection,Compound sodium chloride injection,Mannitol injection,Glycerol fructose and sodium chloride injection,Sodium lactate Ringer’s injection,Glucose and sodium chloride injection,250 m L each respectively,and then sealed in the dark at the room temperature. The appearance of mixtures were observed,p H value,the number of insoluble particles,maximal absorption wavelength and maximal absorbance were detected,and the contents of salvianolic acid B,rosmarinic acid,lithospermic acid and salvianolic acid Y in mixtures were determined by HPLC at 0,1,2,4,8 h after mixing. RESULTS:Under above condition,no obvious change was found in appearance or p H values of the mixtures within 8 h. Maximal absorption wavelength ranged 284.5-286.0 nm. After mixed with Mannitol injection,the number of particles ≥10 μm(1-8 h after mixing)and particles ≥25 μm(4-8 h after mixing)exceeded the scope of Chinese Pharmacopoeia(2015 edition);the maximal absorbance changed significantly(RSD=9.17%,n=5);the relative content of salvianolic acid B,rosmarinic acid,lithospermic acid and salvianolic acid Y decreased by more than 10%(RSD=14.65%,6.45%,8.97%,12.49%,n=5);after mixed with Sodium lactate Ringer’s injection,the relative content of rosmarinic acid and lithospermic acid changed greatly(RSD=14.57%,7.28%,n=5);after mixed with 5% Glucose injection(4-8 h after mixing)and Glycerol fructose and sodium chloride injection(8h after mixing),the relative content of rosmarinic acid were less than 90%(RSD=6.30%,4.86%,n=5);and the number of particles ≥25 μm exceeded the scope of phamcopoeia after mixing with Glycerol fructose and sodium injection(0 h). The number of insoluble particles in other mixtures were in line with the standard of pharmacopoeia;maximal absorbance had no significant change(RSD<5%,n=5),and the relative content change of analytes were all less than 10%. CONCLUSIONS:Clinical application of SAFI combined with Mannitol injection,Sodium lactate Ringe’s injection and Glycerol fructose and sodium injecrion should be avoided. After mixed with 5% Glucose injection,SAFI should be used within 4 h. SAFI can be compatible with 0.9%Sodium chloride injection,10% Glucose injection,Compound sodium chloride injection and Glucose and sodium chloride injection.更多还原