UPLC-MS/MS测定复方甘草口服溶液中4种生物碱含量

Quantitative Determination of 4 Alkaloids in Compound Glycyrrhiza Oral Solution by UPLC-MS/MS

关键词:  复方甘草口服溶液  吗啡  可待因  罂粟碱  可卡因  超高效液相色谱-质谱联用  多反应监测

Key words:  compound glycyrrhiza oral solution  morphine  codeine  papaverine  cocaine  UPLC-MS/MS  multiple reaction monitoring

摘要:

目的 采用超高效液相色谱-质谱联用方法同时测定复方甘草口服溶液中吗啡、可待因、罂粟碱和可卡因的含量。方法 采用Waters BEH C₁₈(50 mm×2.1 mm，1.7 μm)色谱柱，流动相为含0.1%甲酸的0.02 mol·L^-1乙酸铵溶液(A)-甲醇(B)，梯度洗脱(0~1.5 min，92%A；1.5~2.0 min，92%A→60%A；2.0~4.5 min，60%A；4.5~4.6 min，60%A→92%A；4.6~5.0 min，92%A)，流速为0.2 mL·min^-1，柱温为35 ℃；质谱采用电喷雾离子源，多反应监测模式(正离子)。结果 吗啡、可待因、罂粟碱和可卡因浓度分别在5.68~113.4，1.04~20.85，0.53~10.58和0.16~3.13 μg·L^-1内线性关系良好，r值为0.998 4~0.999 9，平均回收率为98.8%~100.3%，定量下限分别为0.5，0.5，0.05，0.01 μg·L^-1，检测限为0.2，0.2，0.02，0.005 μg·L^-1。结论 该方法分析速度快，灵敏度高，结果准确可靠，是复方甘草口服溶液质量控制的一种可行方法。

Abstract:

OBJECTIVE To establish a method for the quantitative determination of 4 alkaloids in compound glycyrrhiza oral solution by UPLC-MS/MS. METHODS Chromatography was carried on a Waters BEH C₁₈ column(50 mm×2.1 mm, 1.7 μm) with the mobile phase consisting of 0.02 mol·L^-1 ammonium acetate water solution(containing 0.1% formic acid)(A) and methanol(B) in a programme of gradient elution(0-1.5 min, 92%A; 1.5-2.0 min, 92%A→60%A; 2.0-4.5 min, 60%A; 4.5-4.6 min, 60%A→92%A; 4.6-5.0 min, 92%A). The flow rate was 0.2 mL·min^-1 with a column temperature at 35 ℃. Determination was performed by multiple reaction monitoring mode using electrospray ionization in positive ion mode. RESULTS The linear ranges of morphine, codeine, papaverine and cocaine were 5.68-113.4, 1.04-20.85, 0.53-10.58 and 0.16-3.13 μg·L^-1 (r=0.998 4-0.999 9). The average recoveries were 98.8%-100.3%. The limits of quantitation and detection were 0.5, 0.5, 0.05, 0.01 μg·L^-1 and 0.2, 0.2, 0.02, 0.005 μg·L^-1, respectively. CONCLUSION The method is rapid, sensitive and accurate, and can be an appropriate technique for quality control of compound glycyrrhiza oral solution.