Skip to content
2000
  1. Home
  2. A-Z Publications
  3. Current Pharmaceutical Analysis
  4. Volume 20, Issue 7
  5. Article
Volume 20, Issue 7
  • ISSN: 1573-4129
  • E-ISSN: 1875-676X

Abstract

Objectives

Difenidol is widely used in clinical practice due to its good anti-dizziness effect and low side effect rate. This aim was to develop an ultra-high performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method for the selective and straightforward measurement of diphenidol in mouse plasma.

Methods

A total of eighteen mice were divided into three groups: six for intravenous administration at a dose of 0.2 mg/kg, six for oral administration at a dose of 0.4 mg/kg, and another six for oral administration at a dose of 1.6 mg/kg. The analytes were extracted using acetonitrile-mediated protein precipitation following the addition of the internal standard (IS), midazolam. On an Acquity HSS T3 column (50 mm × 2.1 mm, 1.8 μm). The quantification process involved the use of multiple reactions monitoring (MRM) mode, with target fragment ions m/z 310.2→128.9 for diphenidol and m/z 326.2→291.4 for IS.

Results

For diphenidol, calibration curves showed a linear distribution between 0.2 and 50 ng/mL. The accuracy of the method was between 94.6% and 110.4%, and the mean recovery of diphenidol in mouse plasma was over 76.5%. The intra-day and inter-day precision RSDs were both limited to 14%. The bioavailability of diphenidol in mice was determined to be 19.9% and 23.56% for the oral dose of 0.4 mg/kg and 1.6 mg/kg, respectively.

Conclusion

The UPLC-MS/MS was successfully applied to study the pharmacokinetics of diphenidol in mice, to which it was administered orally and intravenously.

© 2024 Bentham Science Publishers
Loading

Article metrics loading...

/content/journals/cpa/10.2174/0115734129329904240731105655
2024-08-08
2025-01-22

  • From This Site

    /content/journals/cpa/10.2174/0115734129329904240731105655
    dcterms_title,dcterms_subject,pub_keyword
    -contentType:Contributor -contentType:Concept -contentType:Institution
    10
    5
Loading full text...

Full text loading...

References

  1. NiuW. RenT. WangY. WangZ. ZhangC. JiaJ. WeiZ. SuH. GuoZ. GuoX. YunK. Forensic toxicokinetics of difenidol hydrochloride in vivo verified by practical lethal cases.Sci. Rep.20231311119010.1038/s41598‑023‑38246‑y37433899
     [Google Scholar]
  2. Marcelín-JiménezG. Morales-MartínezM. Ángeles-MorenoA.P. Mendoza-MoralesL. Ultra-fast chromatographic micro-assay for quantification of diphenidol in plasma: application in an oral multi-dose switchability trial.Biomed. Chromatogr.200822101143114810.1002/bmc.103718506741
     [Google Scholar]
  3. YangY. LeiF.Z. DongY.Y. MaJ.L. ShiQ.Q. YeX.S. Retrospective analysis of death cases of oral diphenidol hydrochloride poisoning.Fa Yi Xue Za Zhi202339439339837859479
     [Google Scholar]
  4. YangL. ZhaoJ. LiuM. LiL. YangH. GuoC. HuJ. XiangP. ShenB. QiaoZ. DangY. ShiY. Identifying metabolites of diphenidol by liquid chromatography-quadrupole/orbitrap mass spectrometry using rat liver microsomes, human blood, and urine samples.Drug Test. Anal.20211361127113510.1002/dta.301233554459
     [Google Scholar]
  5. HernándezJ. Marcelín-JiménezG. RiveraL. AlionkaP.Á. ContrerasL. HinojosaM. Martínez-RossierL. AmancioO. FernándezA. Development of an HPLC method for determination of diphenidol in plasma and its application in an oral multi- dose bioequivalence study in a healthy female mexican population.J. Pharm. Biomed. Anal.200538474675010.1016/j.jpba.2005.01.03715967303
     [Google Scholar]
  6. SatoG. MatsudaK. MatsuokaM. FukudaJ. MoritaY. TakahashiK. HoriiA. TakedaN. Comparative study of anti-vertiginous and anti-anxious drugs for the treatment of chronic vestibular patients with secondary anxiety.Acta Otolaryngol.2019139759359710.1080/00016489.2019.161253131107129
     [Google Scholar]
  7. LeungY.M. WongK.L. ChengK.S. KuoC.S. SuT.H. ChenY.W. ChengT.H. Inhibition of voltage-gated K+ channels and Ca2+ channels by diphenidol.Pharmacol. Rep.201264373974410.1016/S1734‑1140(12)70869‑122814027
     [Google Scholar]
  8. LeungY.M. WuB.T. ChenY.C. HungC.H. ChenY.W. Diphenidol inhibited sodium currents and produced spinal anesthesia.Neuropharmacology20105871147115210.1016/j.neuropharm.2010.02.00720176039
     [Google Scholar]
  9. YangL. ShenM. XiangP. ShenB. DengH. QiangH. DangY. ShiY. Application of a validated uplc–ms-ms method for the determination of diphenidol in biological samples in 15 authentic lethal cases.J. Anal. Toxicol.202145997698410.1093/jat/bkaa16033048121
     [Google Scholar]
  10. FDA, U.F.a.D.A. bioanalytical method validation guidance for industry.2018Available from: https://www.fda.gov/regulatory-information/search-fda-guidance-documents/bioanalytical-method-validation-guidance-industry(accessed on 21-7-2024)
  11. ChenF. WangZ. LuoL. HeY. MaY. WenC. WangX. ShenX. Development of an ultra-high-performance liquid chromatography–tandem mass spectrometry method for the simultaneous determination of crassicauline A, fuziline, karacoline, and songorine in rat plasma and application in their pharmacokinetics.Biomed. Chromatogr.2024384e582110.1002/bmc.582138217347
     [Google Scholar]
  12. ZhouA. YuJ. WuY. XueH. ZhongD. DiaoX. A validated LC-MS/MS method for the quantification of bevacizumab in rat, cynomolgus monkey, and human serum.J. Pharm. Biomed. Anal.202323511559010.1016/j.jpba.2023.11559037536114
     [Google Scholar]
  13. WangL. ShenH. ZhanY. ZhangY. ZhangY. ChenM. LiX. ZhongD. Simultaneous quantification of 3′,4′-dimethoxy flavonol-3-O-glucoside and its major metabolite in human plasma by LC-MS/MS and its application to a clinical pharmacokinetic study.J. Pharm. Biomed. Anal.202322511520310.1016/j.jpba.2022.11520336566723
     [Google Scholar]
  14. ShenX. WangZ. LiW. MeiS. MaS. WangX. WenC. ChenF. ZhengG. Pharmacokinetics of ziyuglycoside i and ziyuglycoside ii in rat plasma by UPLC-MS/MS.Int. J. Anal. Chem.202420241810.1155/2024/797102138463657
     [Google Scholar]
  15. RygaardK. PanM. NielsenM.K.K. DalsgaardP.W. RasmussenB.S. LinnetK. Overview of systematic toxicological analysis strategies and their coverage of substances in forensic toxicology.Anal. Sci. Adv.202343-49610310.1002/ansa.20220006238715924
     [Google Scholar]
  16. KokilambigaiK.S. IrinaV.M. Sheba MariamK.C. AdilaK. KathirvelS. Comprehensive overview of analytical and bioanalytical methodologies for the opioid analgesics - Tramadol and combinations.Anal. Biochem.202469211557910.1016/j.ab.2024.11557938797485
     [Google Scholar]
/content/journals/cpa/10.2174/0115734129329904240731105655
Loading
Determination of Diphenidol in Mouse Plasma and Application to a Pharmacokinetic Study Using Uplc-Ms/Ms
Current Pharmaceutical Analysis 20, 640 (2024); https://doi.org/10.2174/0115734129329904240731105655
/content/journals/cpa/10.2174/0115734129329904240731105655
/content/journals/cpa/10.2174/0115734129329904240731105655
Loading

Data & Media loading...


  • Article Type:     Research Article
Keyword(s): bioavailability; Diphenidol; mice; pharmacokinetics; plasma; UPLC-MS/MS

Most Cited Most Cited RSS feed

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error
Please enter a valid_number test