硫酸西索米星原料药及注射剂中硫酸西索米星高效液相色谱—示差折光检测器法含量测定研究
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摘要
硫酸西索米星为新一代的氨基糖苷类抗生素,在临床上的运用广泛,因为它不仅弥补了传统氨基糖苷类抗生素的不足,而且较于传统氨基糖苷类抗生素,它的抗菌谱更加广泛。硫酸西索米星制剂产品的广泛使用无疑对其检测方法特别是有效成分的测定方法提出了更高的要求。
目前本单位所依据的检测方法为微生物检定法,但是此方法存在很多缺陷,比如数据重复性较差、检验环境要求比较苛刻以及检验过程比较冗长等。所以本文在现有检测方法与各种研究资料的基础上,建立了以示差折光检测器-高效液相法来检测硫酸西索米星及注射剂中硫酸西索米星的含量。其中色谱柱采用C_(18)柱(4.6×250mm,5μm),流动相为0.02mol/1三氟醋酸:甲醇(95:5),流速为1.0ml/min,柱温为35℃。同时本文对所建立的方法进行方法学验证,对于硫酸西索米星原料,回收率为99.3%,硫酸西索米星注射液回收率为99.4%。该方法在浓度为0.1mg/m1-2.5mg/ml之间线性回归方程为Y=261623X+6183,r=0.9995。
通过方法学验证以及与现有检测方法的比较,结果表明所建立的方法简便、准确、专属性好,能满足质量控制与生产的要求并且避免了现有检测方法的诸多缺点。
Sisomicin sulfate is a new generations of Aminoglycoside antibiotics, which is widely applied in clinical practice. It not only makes up deficiency of traditional Aminoglycoside antibiotics, but also has broad Antibacterial spectrum compared to traditional ones. It puts forward higher requirements of its analytical method, especially for the active component determination, because of the wide application of sisomicin sulfate formulations.
The current analytical method is microbiological test in our company, and there are some deficiencies such as data repeatability being not good, high requirement for environment. The Differential refraction-HPLC detector method is established on current analytical method and relevant research literatures. Chromatographic column is C_(18) column (4.6×250mm, 5μm), mobile phase is a mixture of 0.02mol/l trifluoroacetic acid: methanol (95:5), flow rate is 1.0ml/min and column temperature is 35℃. Moreover, methodological validation of the method is performed: the recovery is 99.3% for Sisomicin sulfate API, 99.4% for Sisomicin sulfate injection. The linearity equation is Y=261623X+6183, r=0.9995 for concentrations between 0.1 mg/ml and 2.5mg/ml.
Through methodological validation and compared to current method, the established method is more convenient, accurate and specific, which is able to satisfy the requirements of quality control and production.
目前本单位所依据的检测方法为微生物检定法,但是此方法存在很多缺陷,比如数据重复性较差、检验环境要求比较苛刻以及检验过程比较冗长等。所以本文在现有检测方法与各种研究资料的基础上,建立了以示差折光检测器-高效液相法来检测硫酸西索米星及注射剂中硫酸西索米星的含量。其中色谱柱采用C_(18)柱(4.6×250mm,5μm),流动相为0.02mol/1三氟醋酸:甲醇(95:5),流速为1.0ml/min,柱温为35℃。同时本文对所建立的方法进行方法学验证,对于硫酸西索米星原料,回收率为99.3%,硫酸西索米星注射液回收率为99.4%。该方法在浓度为0.1mg/m1-2.5mg/ml之间线性回归方程为Y=261623X+6183,r=0.9995。
通过方法学验证以及与现有检测方法的比较,结果表明所建立的方法简便、准确、专属性好,能满足质量控制与生产的要求并且避免了现有检测方法的诸多缺点。
Sisomicin sulfate is a new generations of Aminoglycoside antibiotics, which is widely applied in clinical practice. It not only makes up deficiency of traditional Aminoglycoside antibiotics, but also has broad Antibacterial spectrum compared to traditional ones. It puts forward higher requirements of its analytical method, especially for the active component determination, because of the wide application of sisomicin sulfate formulations.
The current analytical method is microbiological test in our company, and there are some deficiencies such as data repeatability being not good, high requirement for environment. The Differential refraction-HPLC detector method is established on current analytical method and relevant research literatures. Chromatographic column is C_(18) column (4.6×250mm, 5μm), mobile phase is a mixture of 0.02mol/l trifluoroacetic acid: methanol (95:5), flow rate is 1.0ml/min and column temperature is 35℃. Moreover, methodological validation of the method is performed: the recovery is 99.3% for Sisomicin sulfate API, 99.4% for Sisomicin sulfate injection. The linearity equation is Y=261623X+6183, r=0.9995 for concentrations between 0.1 mg/ml and 2.5mg/ml.
Through methodological validation and compared to current method, the established method is more convenient, accurate and specific, which is able to satisfy the requirements of quality control and production.
引文
铩颷1]吴英梅,西索米星与庆大霉素治疗呼吸道感染比较,广东药学,2001,11(4)
[2]Sisomicin Sulfate,U.S.PHARMATICOPEIA The Standard of Quality~(SM)
[3]Sisomicin Sulfate,日本药局方 第十三册改正
[4]硫酸西索米星,硫酸西索米星注射液,中华人民共和国2005年版药典二部:727
[5]陈珠灵等,衍生化-高效液相色谱法测定西索米星,分析实验室,2002,21(3)
[6]袁成等,高效液相色谱-间接光度法测定体液中西梭霉素,色谱,1998,16(5)
[7]袁成等,高效液相色谱-间接光度法同时测定血清和尿样中5种氨基糖苷类抗生素,药物分析杂志,1999,19(2)
[8]于华生等,HPLC-ELSD法测定硫酸西索米星氯化钠注射液中西索米星含量,Strait Pharmaceutical Journal 2004,16(6):41-43
[9]王明娟等,蒸发光散射检测器在氨基糖苷类抗生素分析中的应用探讨,中华临床医学杂志,2004,5(6):35-39
[10]Fluorometric Determination of Sisomicin,an Aminoglycoside Antibiotic,in DriedBlood Spots on Filter Paper by Reversed-Phase High-Performance LiquidChromatography with Pre-column Derivatization,Chem.Pharm.Bull.1988,36(4)
[11]Fluorometric Determination of Sisomicin,an Aminoglycoside Antibiotic byReversed-Phase High-Performance Liquid Chromatography with Pre-columnDerivatization,Chem.Pharm.Bull.1988,36(4)
[12]范铭琦等,西索米星原料药中极性小组分的研究,中国抗生素杂志,1998,23(3)
[13]张春跃,同一种方法鉴别三种氨基糖苷类抗生素,首都医药2001,8(10):40
[14]Inchaupe G,Delrien P,Mechanism of selectivity in ion-pair high-performanceliquidchromatogtaphy of aminoglycosides antibiotics using perfluorinated pairing ions,Jchromatogr.,1987,404,53
[15]Inchaupe G,Samain D,Use of perfluorinated carboxylic acid in the separation ofantibiotics by ion-pair reversed-phase high -performance liquid chromatography,J chromatogr.,1984,303,277
铩颷16]Tomii,Takao,Penetration of antimicrobial agents into the aqueous humor followingtopical administration.Ⅰ.Determination of sisomicin sulfate with flurorometricpre-column derivatization(HPLC),Atarashii Ganka 1998,5(1)
[17]Fujimotc,Takshi,Determination of sisomicin in eluate from dried blood spots onfilter paper disk for monitoring of bloods level in rats,by reversed-phasehigh-performance liquid chromatography after pre-column fluocimetric derivatization.Chem.Pharm.Bull,1989,37(1)
[18]Clarot,I;Determination of gentamicin sulfate and related compound byhigh-performance liquid chromatography with evaporative light scattering detection,Journal of Chromatography,A 2004
[19]张星等,旋光法测定西梭霉素的含量,海峡药学,2003,15(1)
[20]宋尚龙等,旋光法测定硫酸西索米星注射液半成品的含量,2006 15(16):18
[21]王建、李忠红等,高效液相色谱.电喷雾离子阱质谱法分析6种氨基糖甙类抗生素,分析化学研究简报,2006,34(7):979-982
[22]施燕支等,HPLC示差折光分析法测定口香糖中的木糖醇等多种糖醇的含量,首都师范大学学报,2005,26(1)
[23]陈江峰等,在发酵肉汤中用薄层色谱-生物自动检定法测定西索米星,抗生素杂志,2002,27(4)
[23]ICH Harmonized Tripartite Guideline,ICH Q2A,Text on validation of AnalyticalProcedures,Mar.1995
[24]ICH Harmonized Tripartite Guideline,ICH Q2B,Validation of AnalyticalProcedures:Methods,May.1997
[25]ICH Harmonized Tripartite Guideline,ICH Q3B(R),Impurities in New DrugProducts,Oct.1999
[26]FDA Guidance for Industry:analytical procedures and methods validation,chemistry,manufacturing,and controls documentation(Draft),2000.8
[27]中华人民共和国药典二部《药品质量标准分析方法验证指导原则》:附录173
[28]CHUNG CHOW CHAN,HERMAN LAM,Analytical Method Validation andInstrument Performance Verification
铩颷29]吴燕等,HPLC-ELSD法测定硫酸奈替米星与硫酸西索米星氯的含量与有关物质,中国药品标准,2004,5(4):35-39
[30]吴燕等,氨基糖苷类抗生素分析方法进展,天津药学2004,17(1):46-48
[31]Sisomicin sulfate,Sisomicin sulfate injection,U.S.pharmacopeia 30:3181-3182
[2]Sisomicin Sulfate,U.S.PHARMATICOPEIA The Standard of Quality~(SM)
[3]Sisomicin Sulfate,日本药局方 第十三册改正
[4]硫酸西索米星,硫酸西索米星注射液,中华人民共和国2005年版药典二部:727
[5]陈珠灵等,衍生化-高效液相色谱法测定西索米星,分析实验室,2002,21(3)
[6]袁成等,高效液相色谱-间接光度法测定体液中西梭霉素,色谱,1998,16(5)
[7]袁成等,高效液相色谱-间接光度法同时测定血清和尿样中5种氨基糖苷类抗生素,药物分析杂志,1999,19(2)
[8]于华生等,HPLC-ELSD法测定硫酸西索米星氯化钠注射液中西索米星含量,Strait Pharmaceutical Journal 2004,16(6):41-43
[9]王明娟等,蒸发光散射检测器在氨基糖苷类抗生素分析中的应用探讨,中华临床医学杂志,2004,5(6):35-39
[10]Fluorometric Determination of Sisomicin,an Aminoglycoside Antibiotic,in DriedBlood Spots on Filter Paper by Reversed-Phase High-Performance LiquidChromatography with Pre-column Derivatization,Chem.Pharm.Bull.1988,36(4)
[11]Fluorometric Determination of Sisomicin,an Aminoglycoside Antibiotic byReversed-Phase High-Performance Liquid Chromatography with Pre-columnDerivatization,Chem.Pharm.Bull.1988,36(4)
[12]范铭琦等,西索米星原料药中极性小组分的研究,中国抗生素杂志,1998,23(3)
[13]张春跃,同一种方法鉴别三种氨基糖苷类抗生素,首都医药2001,8(10):40
[14]Inchaupe G,Delrien P,Mechanism of selectivity in ion-pair high-performanceliquidchromatogtaphy of aminoglycosides antibiotics using perfluorinated pairing ions,Jchromatogr.,1987,404,53
[15]Inchaupe G,Samain D,Use of perfluorinated carboxylic acid in the separation ofantibiotics by ion-pair reversed-phase high -performance liquid chromatography,J chromatogr.,1984,303,277
铩颷16]Tomii,Takao,Penetration of antimicrobial agents into the aqueous humor followingtopical administration.Ⅰ.Determination of sisomicin sulfate with flurorometricpre-column derivatization(HPLC),Atarashii Ganka 1998,5(1)
[17]Fujimotc,Takshi,Determination of sisomicin in eluate from dried blood spots onfilter paper disk for monitoring of bloods level in rats,by reversed-phasehigh-performance liquid chromatography after pre-column fluocimetric derivatization.Chem.Pharm.Bull,1989,37(1)
[18]Clarot,I;Determination of gentamicin sulfate and related compound byhigh-performance liquid chromatography with evaporative light scattering detection,Journal of Chromatography,A 2004
[19]张星等,旋光法测定西梭霉素的含量,海峡药学,2003,15(1)
[20]宋尚龙等,旋光法测定硫酸西索米星注射液半成品的含量,2006 15(16):18
[21]王建、李忠红等,高效液相色谱.电喷雾离子阱质谱法分析6种氨基糖甙类抗生素,分析化学研究简报,2006,34(7):979-982
[22]施燕支等,HPLC示差折光分析法测定口香糖中的木糖醇等多种糖醇的含量,首都师范大学学报,2005,26(1)
[23]陈江峰等,在发酵肉汤中用薄层色谱-生物自动检定法测定西索米星,抗生素杂志,2002,27(4)
[23]ICH Harmonized Tripartite Guideline,ICH Q2A,Text on validation of AnalyticalProcedures,Mar.1995
[24]ICH Harmonized Tripartite Guideline,ICH Q2B,Validation of AnalyticalProcedures:Methods,May.1997
[25]ICH Harmonized Tripartite Guideline,ICH Q3B(R),Impurities in New DrugProducts,Oct.1999
[26]FDA Guidance for Industry:analytical procedures and methods validation,chemistry,manufacturing,and controls documentation(Draft),2000.8
[27]中华人民共和国药典二部《药品质量标准分析方法验证指导原则》:附录173
[28]CHUNG CHOW CHAN,HERMAN LAM,Analytical Method Validation andInstrument Performance Verification
铩颷29]吴燕等,HPLC-ELSD法测定硫酸奈替米星与硫酸西索米星氯的含量与有关物质,中国药品标准,2004,5(4):35-39
[30]吴燕等,氨基糖苷类抗生素分析方法进展,天津药学2004,17(1):46-48
[31]Sisomicin sulfate,Sisomicin sulfate injection,U.S.pharmacopeia 30:3181-3182
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