| 盐酸苯海拉明咖啡因复方在大鼠体内的药动学研究 |
| 投稿时间：2021-06-16 修订日期：2021-08-31 点此下载全文 |
| 引用本文：高宇,凌琳,邢信昊,赵亮,王欣荣,王彦.盐酸苯海拉明咖啡因复方在大鼠体内的药动学研究[J].药学实践杂志,2021,39(5):415~421 |
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| 基金项目:国家科技重大专项（2018ZX09J18110-002-002） |
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| 中文摘要:目的 建立UPLC-MS/MS方法测定大鼠血浆中盐酸苯海拉明与咖啡因的浓度，用于药动学研究。方法 色谱柱为ACE 3 C18-PFP（3.0 mm×150 mm，3 μm），流动相系统采用0.1%甲酸水溶液-乙腈（62∶38，V/V），等度洗脱；质谱采用AJS-ESI离子源，正离子模式，多重反应监测（MRM），盐酸苯海拉明256.2.0→167.0（m/z），盐酸苯海拉明-D6（IS）262.0→167.0（m/z），咖啡因 195.0→138.0（m/z），内标咖啡因-D9（IS）204.0→116.2（m/z）。结果 大鼠血浆中盐酸苯海拉明在1～1×103 ng/ml范围内线性关系良好（r=0.999 6），定量下限1 ng/ml；咖啡因在15～1.5×105 ng/ml范围内线性关系良好（r=0.999 9），定量下限15 ng/ml。盐酸苯海拉明和咖啡因低、中、高3个浓度水平的日内和日间精密度和准确度均良好（RSD<10%，RE<±10%）。药动学研究结果显示，灌胃给予盐酸苯海拉明10～30 mg/kg和咖啡因24～72 mg/kg后，药动学参数呈线性代谢动力学特征；同时两种成分在大鼠体内代谢存在性别差异，雌性大鼠灌胃给药后，体内盐酸苯海拉明及咖啡因的达峰浓度（cmax）及药时曲线下面积（AUC）均大于雄性。结论 该方法准确、快速且灵敏度高，能准确检测大鼠血浆样品中的盐酸苯海拉明和咖啡因的浓度用于药动学研究，大鼠体内药动学研究结果为该复方的临床应用提供了可靠的数据支持。 |
| 中文关键词:盐酸苯海拉明 咖啡因 超高效液相串联质谱法 含量测定 药动学 |
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| The pharmacokinetic study on compound diphenhydramine hydrochloride and caffeine in rats |
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| Abstract:Objective To establish an assay method for diphenhydramine hydrochloride and caffeine in rat plasma by UPLC-MS/MS for pharmacokinetic study. Methods The chromatographic separation was performed on an ACE 3 C18-PFP (3.0 mm×150 mm, 3 μm) by isocratic elution with the mobile phase of water containing 0.1% formic acid and acetonitrile (62:38, V/V). MS condition was optimized in the positive ion detection mode by multiple reaction monitoring (MRM), along with the Agilent JetStream electrospray source interface (AJS-ESI). The precursors to the product ion transitions were 256.2→167.0 (m/z) for diphenhydramine hydrochloride, 262.0→167.0 (m/z) for the internal standard (IS) diphenhydramine-D6, 195.0→138.0 (m/z) for caffeine and 204.0→116.2 (m/z) for the IS caffeine-D9. Results The calibration curve was linear in the range of 1-1×103 ng/ml for diphenhydramine hydrochloride in rat plasma (r=0.999 6), and in the range of 15-1.5×105 ng/ml for caffeine in rat plasma, (r=0.999 9). The intra-day and inter-day precision and accuracy were good (RSD<10%, RE<±10%). Pharmacokinetic studies showed that metabolic characteristics of diphenhydramine hydrochloride 10-30 mg/kg and caffeine 24-72 mg/kg were linear after intragastric administration. The two components were metabolized in rats with gender difference, the cmax and the AUC of diphenhydramine hydrochloride and caffeine were greater in female than those in males. Conclusion This method is accurate, rapid and sensitive. It can be used for the determination of diphenhydramine hydrochloride and caffeine in rat plasma collected for pharmacokinetic study. The results of pharmacokinetic studies in rats provide reliable data support for the clinical application of the compound preparation. |
| keywords:diphenhydramine hydrochloride caffeine UPLC-MS/MS content determination pharmacokinetic |
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