The pharmacokinetic study on compound diphenhydramine hydrochloride and caffeine in rats
10.12206/j.issn.1006-0111.202106091
- VernacularTitle:盐酸苯海拉明咖啡因复方在大鼠体内的药动学研究
- Author:
Yu GAO
1
;
Lin LING
2
;
Xinhao XING
3
;
Liang ZHAO
4
;
Xinrong WANG
3
;
Yan WANG
3
Author Information
1. The Seventh Medical Center of the PLA General Hospital, Beijing 1007002, China.
2. College of Pharmaceutical Science, Zhejiang University of Technology, Hangzhou 310014, China.
3. Center for Drug Discovery and Development, School of Pharmacy, Naval Medical University, Shanghai 200433, China.
4. Department of Pharmacy, Shanghai Baoshan Luodian Hospital, Shanghai 201908, China.
- Publication Type:Originalarticles
- Keywords:
diphenhydramine hydrochloride;
caffeine;
UPLC-MS/MS;
content determination;
pharmacokinetic
- From:
Journal of Pharmaceutical Practice
2021;39(5):415-421
- CountryChina
- Language:Chinese
-
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.
