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

Hernández, José Antonio; Marcelín‐Jiménez, Gabriel; Rivera, Luis Javier Marfil; Alionka, P. Ángeles; Contreras, L.; Hinojosa, María Ignacia Martín de la; Martínez-Rossier, L.; Amancio, O.; Fernández, Ana Patricia

doi:10.1016/j.jpba.2005.01.037

Cited by 9 publications

(6 citation statements)

References 7 publications

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“…During the first day of the analytical phase, the samples of volunteers 1-3 were lost; thus, the study was concluded with 21 subjects with no consequences for the statistical power (>80%). Pharmacokinetic parameters were compared with those previously reported (Hernández et al, 2005), and except for C max (nearly 30% lower in the present study), there were no significant differences between both trials. There is one significant condition that may explain such a difference in C max , the use of a male population in the present trial.…”

Section: Pharmacokineticssupporting

confidence: 59%

“…The signalto-noise ratio was 11:1 (CV < 15%) for the low limit of quantification, which was 10 times lower than previously reported. Our method is 20,000 times more sensitive in terms of the amount of DPN per injection, compared with the previously reported technique (Hernández et al, 2005).…”

Section: Linearity and Low Limit Of Quantificationmentioning

confidence: 68%

“…One of the first efforts in the present work was the attempt to diminish the amount of plasma used in the unique method previously reported (2 mL), maintaining the same liquid-liquid extraction (hexane-ethyl etherisobutyl alcohol, 70:25:5 v/v; Hernández et al, 2005). Although extraction of 200 μL of plasma gave satisfactory analytical results, we decided to attempt this with direct precipitation based on the high intensity of the signal obtained during DPN tuning.…”

Section: Sample Handling and Extractive Proceduresmentioning

confidence: 99%

“…The pharmacokinetics has been previously reported in an oral multi-dose trial in healthy female Mexican volunteers, in which peak plasma concentrations were reported between 0.5 and 1.5 h post-dose, and an elimination half-life ca 3 h was calculated during steady state (Hernández et al, 2005). These data were obtained with the unique method previously mentioned: an HPLC technique coupled with UV detection; although this was validated and applied in a bioequivalence trial, it is time-consuming and requires the processing of 2 mL of plasma to reach a moderate sensitivity level (40 ng/mL).…”

Section: Introductionmentioning

confidence: 99%

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Ultra‐fast chromatographic micro‐assay for quantification of diphenidol in plasma: application in an oral multi‐dose switchability trial

Marcelín‐Jiménez

Morales-Martínez

Ángeles-Moreno

et al. 2008

Biomedical Chromatography

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Pharmacokinetics of diphenidol (DPN) is limited due to the lack of analytical methodology. Here, a micro-assay for DPN quantification was developed, by coupling ultra-performance liquid chromatography with tandem mass spectrometry. The procedure involved plasma precipitation and injection of supernatant into UPLC with an Acquitytrade mark C18 column. Detection was in positive electrospray, following transitions of m/z 310.3 --> 292.3 and m/z 275.3 --> 230.2 for DPN and chlorphenamine (internal standard), respectively. The method was linear with a range of 4-400 ng/mL, and a 2 min run time. This method was applied in a switchability trial, where both formulations of DPN were bioequivalent.

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Section: Pharmacokineticssupporting

confidence: 59%

Section: Linearity and Low Limit Of Quantificationmentioning

confidence: 68%

Section: Sample Handling and Extractive Proceduresmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Ultra‐fast chromatographic micro‐assay for quantification of diphenidol in plasma: application in an oral multi‐dose switchability trial

Marcelín‐Jiménez

Morales-Martínez

Ángeles-Moreno

et al. 2008

Biomedical Chromatography

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“…The peak plasma concentrations were reported to be between 0.5-and 1.5-h postdose, and an elimination half-life of approximately 3 h was calculated in an oral multidose trial in healthy female Mexican volunteers. 15,16 Thus far, metabolite identification is still full of challenges, as most metabolites are unpredictable and present in low concentrations in biological samples. With the development of mass spectrometry, high-resolution mass spectrometry (HRMS) improve the sensitivity and information content of overall approaches by achieving accurate mass measurements with sub-ppm errors.…”

Section: Kaiser Et Al Inferred Several Potential Metabolites Of Diphenidol Basedmentioning

confidence: 99%

Identifying metabolites of diphenidol by liquid chromatography‐quadrupole/orbitrap mass spectrometry using rat liver microsomes, human blood, and urine samples

Yang

Zhao²,

Liu³

et al. 2021

Drug Testing and Analysis

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In recent years, diphenidol [1,1-diphenyl-4-piperidino-1-butanol] has been one of the drugs that appears in suicide cases, but there are few research data on its metabolic pathways and main metabolites. Metabolite identification plays a key role in drug safety assessment and clinical application. In this study, in vivo and in vitro samples were analyzed with ultra-high-performance liquid chromatographyquadrupole/electrostatic field orbitrap high-resolution mass spectrometry. Structural elucidation of the metabolites was performed by comparing their molecular weights and product ions with those of the parent drug. As a result, 10 Phase I metabolites and 5 glucuronated Phase II metabolites were found in a blood sample and a urine sample from authentic cases. Three other Phase I metabolites were identified in the rat liver microsomes incubation solution. The results showed that the main metabolic

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Fatal diphenidol poisoning: a case report and a retrospective study of 16 cases

Zhang

Li³

et al. 2015

Forensic Sci Med Pathol

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Diphenidol hydrochloride (DPN), a nonphenothiazinic antiemetic agent used primarily in patients with Meniere disease and labyrinthopathies to treat vomiting and vertigo, is considered to be a relatively safe drug. Since it was first approved in the United States in 1967, this drug has been widely used in Latin America and Asia and has contributed to sporadic suicidal and accidental poisonings in mainland China and Taiwan. However, its toxic or lethal concentration ranges have not yet been determined. We report a case of a 23-year-old female who suffered from DPN poisoning that resulted in death. At autopsy, there were no typical pathological findings, except for cerebral edema with high acetylcholinesterase expression. Postmortem analysis of DPN revealed 45 µg/ml in heart blood, 39 µg/ml in femoral vein blood, 141 µg/g in the liver, and 53 mg in the gastric contents. These concentrations indicated that the cause of death was DPN poisoning. The circumstances indicated that the manner of death was suicide. We also present a retrospective study, in which we review and summarize the literature from 1998 to 2014 and describe 16 cases of poisoning, including information from autopsy reports and postmortem drug concentrations. In forensic practice, drug residues at the scene, patients with convulsions and disturbance of consciousness, and rapidly occurring deaths, should draw attention to the possibility of this drug. Toxicological analysis and the exclusion of other diseases may ultimately be used to confirm DPN poisoning.

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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

Cited by 9 publications

References 7 publications

Ultra‐fast chromatographic micro‐assay for quantification of diphenidol in plasma: application in an oral multi‐dose switchability trial

Ultra‐fast chromatographic micro‐assay for quantification of diphenidol in plasma: application in an oral multi‐dose switchability trial

Identifying metabolites of diphenidol by liquid chromatography‐quadrupole/orbitrap mass spectrometry using rat liver microsomes, human blood, and urine samples

Fatal diphenidol poisoning: a case report and a retrospective study of 16 cases

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