| 引用本文: | 刘秋梅,田卫伟,喻光燚,温美强,任雅楠,赵琪,张丽锋.柱前衍生-HPLC测定白消安在家兔体内的药动学参数[J].中国现代应用药学,2018,35(9):1308-1313. |
| LIU Qiumei,TIAN Weiwei,YU Guangyi,WEN Meiqiang,REN Yanan,ZHAO Qi,ZHANG Lifeng.Determination of Pharmacokinetic Parameters of Busulfan in Rabbits by Pre-column Derivatization HPLC[J].Chin J Mod Appl Pharm(中国现代应用药学),2018,35(9):1308-1313. |
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| 柱前衍生-HPLC测定白消安在家兔体内的药动学参数 |
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刘秋梅,田卫伟,喻光燚,温美强,任雅楠,赵琪,张丽锋
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山西医科大学药学院,山西医学科学院山西大医院血液内科,山西医科大学药学院,山西医科大学,山西医科大学,山西医科大学,山西医科大学药学院
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| 摘要: |
| 目的 建立测定家兔血清中白消安浓度和家兔体内药动学特征的柱前衍生化HPLC。方法 以1，5-戊二醇二甲磺酸酯为内标，二乙基二硫代氨基甲酸钠为衍生化试剂。流动相：甲醇-水（54∶46），流速：0~20 min（1.0 mL·min-1），20~27 min（1.3 mL·min-1）。柱温：30℃，检测波长：280 nm，进样量：25 μL。家兔分别以灌胃、静注的方式给予白消安，按本法测定血药浓度，DAS 3.0计算药动学参数。结果 白消安的血药浓度在0.1~3.4 mg·-L1 内线性关系良好（r=0.999 7），日内、日间精密度以及样品稳定性符合中国药典2015年版的规定。低、中、高浓度的萃取回收率分别为90.0%，89.0%，91.5%。不同给药途径获得的药动学参数：单剂量口服t1/2=（2.26±0.66）h，k=（0.33±0.12）·h-1，ka=（2.54±1.3）·h-1，AUC0–t=（1.95±0.18）h·mg·mL-1；单剂量静脉注射t1/2=（1.53±0.09）h，k=（0.45±0.03）·h-1，AUC0–∞=（4.38±0.26）h·mg·mL-1。多剂量口服后Css=（0.48±0.03）mg·mL-1，AUC0–τ=（3.87±0.26）h·mg·mL-1。结论 建立的柱前衍生-HPLC法适用于白消安血药浓度测定及药动学研究，不同给药途径的药动学参数为临床药动学研究提供了依据。 |
| 关键词: 白消安 柱前衍生 高效液相色谱法 药动学参数 |
| DOI：10.13748/j.cnki.issn1007-7693.2018.09.008 |
| 分类号:R969.1 |
| 基金项目:山西省重点研发计划（指南）项目（201603D321055）；山西医科大学创新创业校级项目（20170708）；山西省高校重点学科建设专项资金项目（[2016]4号） |
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| Determination of Pharmacokinetic Parameters of Busulfan in Rabbits by Pre-column Derivatization HPLC |
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LiuQiumei,TianWeiwei,YuGuangyi,WenMeiqiang,RenYanan,ZhaoQi and ZhangLifeng
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School of Pharmacy,Shanxi Medical University,Department of Hematology, Shanxi University Hospital of Shanxi Medical Sciences,School of Pharmacy,Shanxi Medical University,School of Pharmacy,Shanxi Medical University,School of Pharmacy,Shanxi Medical University,School of Pharmacy,Shanxi Medical University,School of Pharmacy,Shanxi Medical University
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| Abstract: |
| OBJECTIVE To establish a pre-column derivatization HPLC method which was used for determining the busulfan concentration in serum and pharmacokinetic characteristic of rabbits. METHODS 1,5-pentanediol dimethanesulfonate was used as internal standard, sodium diethyldithiocarbamate was used as derivatization reagent, and the derivatives of the busulfan and the internal standard were eluted with methanol-water (54:46) as mobile phase at a flow rate of 1.0 mL·min-1 (0-20 min), 1.3 mL·min-1 (20-27 min). The column temperature was 30℃, the detective wavelength was 280 nm and the injection volume was 25 μL. The rabbits were given busulfan by intragastric administration and intravenous injection respectively. The busulfan concentration in serum were measured by this method and the DAS 3.0 software was used to calculate pharmacokinetic parameters. RESULTS The blood concentration of busulfan was linear in the range of 0.1-3.4 mg·L-1 (r=0.999 7). The intraday, interday precision and sample stability were in accordance with the 2015 edition of the Chinese Pharmacopoeia. The extraction recoveries of low, medium and high concentrations were 90.0%, 89.0% and 91.5%, respectively. The pharmacokinetic parameters of single dose orally were:t1/2= (2.26±0.66)h, k= (0.33±0.12)·h-1, ka= (2.54±1.3)·h-1, AUC0-t= (1.95±0.18)h·mg·mL-1; those of intravenous injection were:t1/2= (1.53±0.09)h, k= (0.45±0.03)·h-1, AUC0-∞= (4.38±0.26)h·mg·mL-1 and those of multi-dose oral administration were Css= (0.48±0.03)mg·mL-1, AUC0-τ= (3.87±0.26)h·mg·mL-1. CONCLUSION The established method is suitable for determining the concentration of busulfan in serum and studying the pharmacokinetics. The pharmacokinetic parameters of the different routes of administration provide a practical basis for clinical pharmacokinetic studies. |
| Key words: busulfan pre-column derivation HPLC pharmacokinetic parameters |
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