108605
论文已发表
注册即可获取德孚的最新动态
IF 收录期刊
- 3.4 Breast Cancer (Dove Med Press)
- 3.2 Clin Epidemiol
- 2.6 Cancer Manag Res
- 2.9 Infect Drug Resist
- 3.7 Clin Interv Aging
- 5.1 Drug Des Dev Ther
- 3.1 Int J Chronic Obstr
- 6.6 Int J Nanomed
- 2.6 Int J Women's Health
- 2.9 Neuropsych Dis Treat
- 2.8 OncoTargets Ther
- 2.0 Patient Prefer Adher
- 2.2 Ther Clin Risk Manag
- 2.5 J Pain Res
- 3.0 Diabet Metab Synd Ob
- 3.2 Psychol Res Behav Ma
- 3.4 Nat Sci Sleep
- 1.8 Pharmgenomics Pers Med
- 2.0 Risk Manag Healthc Policy
- 4.1 J Inflamm Res
- 2.0 Int J Gen Med
- 3.4 J Hepatocell Carcinoma
- 3.0 J Asthma Allergy
- 2.2 Clin Cosmet Investig Dermatol
- 2.4 J Multidiscip Healthc
已发表论文
高效液相色谱 - 串联质谱法同时检测艾氯胺酮和去甲氯胺酮的开发：应用于右美托咪定影响的药代动力学及药物相互作用
Authors Zhou W, Guo Z, Zhang X, Wang W, Zheng Z, Qiu X
Received 12 July 2025
Accepted for publication 18 September 2025
Published 22 September 2025 Volume 2025:19 Pages 8589—8600
DOI https://doi.org/10.2147/DDDT.S553389
Checked for plagiarism Yes
Review by Single anonymous peer review
Peer reviewer comments 3
Editor who approved publication: Professor Anastasios Lymperopoulos
Wei Zhou,1 Zhe Guo,1 Xianghan Zhang,2 Wenjiong Wang,2 Zhongfeng Zheng,3 Xaingjun Qiu2,3
1Department of Anesthesiology, Nanyang City Central Hospital, Nanyang, Henan, 473009, People’s Republic of China; 2College of Basic Medicine and Forensic Medicine, Henan University of Science and Technology, Luoyang, Henan, 471023, People’s Republic of China; 3Department of Forensic Toxicology, Henan Yicheng Judicial Appraisal Center, Zhengzhou, Henan, 450052, People’s Republic of China
Correspondence: Xaingjun Qiu, College of Basic Medicine and Forensic Medicine, Henan University of Science and Technology, Luoyang, Henan, 471023, People’s Republic of China, Tel +86 13698882699, Email lyxiangjun@126.com
Purpose: Dexmedetomidine (DEX) and esketamine (ESK) are often used together during anesthesia. This study aimed to establish a sensitive and reliable HPLC-MS/MS method for simultaneous quantification of ESK and its active metabolite norketamine (NORK) in beagle dog plasma and to investigate the pharmacokinetic drug-drug interactions (DDIs) between DEX and ESK/NORK.
Methods: A simple protein precipitation method using acetonitrile was applied for plasma sample preparation. After chromatographic separation, analytes were detected by HPLC-MS/MS in positive ion mode using multiple reaction monitoring (MRM). The mass transitions were m/z 238.10→ 125.10 for ESK, m/z 224.10→ 125.10 for NORK, and m/z 354.20→ 209.00 for the internal standard (proadifen). Six beagle dogs were intramuscularly administered 1 mg/kg ESK alone in the first period (ESK group). After a washout, the same dogs received intravenous DEX (2 μg/kg) for 7 consecutive days, followed by co-administration of ESK (DEX+ESK group). The pharmacokinetic parameters of ESK and NORK were calculated using DAS software. Independent-sample t test was used to compare the differences of pharmacokinetic parameters between ESK group and DEX+ESK group, and P < 0.05 indicated a statistically significant difference.
Results: Both ESK and NORK exhibited good linearity within the concentration range of 1– 400 ng/mL, and the methodological validation met the requirements. When ESK was used in combination with DEX, the main pharmacokinetic parameters of ESK and NORK changed, the Cmax, AUC(0– 24) and AUC(0-∞) of ESK increased, the Cmax, of NORK decreased, and the AUC(0– 12) and AUC(0-∞) of NORK increased too.
Conclusion: A novel HPLC-MS/MS method was developed and validated and successfully applied to simultaneously quantify ESK and NORK in beagle dog plasma. The pharmacokinetic DDI results indicate that DEX could inhibit the metabolism of ESK, alter pharmacokinetic characteristics of ESK and its metabolite NORK, and significantly increase the systemic exposure of both ESK and NORK.
Keywords: dexmedetomidine, esketamine, norketamine, pharmacokinetics, drug-drug interactions, beagle dog
1Department of Anesthesiology, Nanyang City Central Hospital, Nanyang, Henan, 473009, People’s Republic of China; 2College of Basic Medicine and Forensic Medicine, Henan University of Science and Technology, Luoyang, Henan, 471023, People’s Republic of China; 3Department of Forensic Toxicology, Henan Yicheng Judicial Appraisal Center, Zhengzhou, Henan, 450052, People’s Republic of China
Correspondence: Xaingjun Qiu, College of Basic Medicine and Forensic Medicine, Henan University of Science and Technology, Luoyang, Henan, 471023, People’s Republic of China, Tel +86 13698882699, Email lyxiangjun@126.com
Purpose: Dexmedetomidine (DEX) and esketamine (ESK) are often used together during anesthesia. This study aimed to establish a sensitive and reliable HPLC-MS/MS method for simultaneous quantification of ESK and its active metabolite norketamine (NORK) in beagle dog plasma and to investigate the pharmacokinetic drug-drug interactions (DDIs) between DEX and ESK/NORK.
Methods: A simple protein precipitation method using acetonitrile was applied for plasma sample preparation. After chromatographic separation, analytes were detected by HPLC-MS/MS in positive ion mode using multiple reaction monitoring (MRM). The mass transitions were m/z 238.10→ 125.10 for ESK, m/z 224.10→ 125.10 for NORK, and m/z 354.20→ 209.00 for the internal standard (proadifen). Six beagle dogs were intramuscularly administered 1 mg/kg ESK alone in the first period (ESK group). After a washout, the same dogs received intravenous DEX (2 μg/kg) for 7 consecutive days, followed by co-administration of ESK (DEX+ESK group). The pharmacokinetic parameters of ESK and NORK were calculated using DAS software. Independent-sample t test was used to compare the differences of pharmacokinetic parameters between ESK group and DEX+ESK group, and P < 0.05 indicated a statistically significant difference.
Results: Both ESK and NORK exhibited good linearity within the concentration range of 1– 400 ng/mL, and the methodological validation met the requirements. When ESK was used in combination with DEX, the main pharmacokinetic parameters of ESK and NORK changed, the Cmax, AUC(0– 24) and AUC(0-∞) of ESK increased, the Cmax, of NORK decreased, and the AUC(0– 12) and AUC(0-∞) of NORK increased too.
Conclusion: A novel HPLC-MS/MS method was developed and validated and successfully applied to simultaneously quantify ESK and NORK in beagle dog plasma. The pharmacokinetic DDI results indicate that DEX could inhibit the metabolism of ESK, alter pharmacokinetic characteristics of ESK and its metabolite NORK, and significantly increase the systemic exposure of both ESK and NORK.
Keywords: dexmedetomidine, esketamine, norketamine, pharmacokinetics, drug-drug interactions, beagle dog