High-throughput assay for simultaneous quantification of the plasma concentrations of morphine, fentanyl, midazolam and their major metabolites using automated SPE coupled to LC–MS/MS

Ghassabian, Sussan; Moosavi, Seyed Mojtaba; Valero, Yarmarly C. Guerra; Shekar, Kiran; Fraser, John F.; Smith, Maree T.

doi:10.1016/j.jchromb.2012.07.005

Cited by 52 publications

(26 citation statements)

References 25 publications

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“…There were some methods reported for detecting morphine or its metabolites. Ghassabian et al simultaneously analyzed morphine, fentanyl, midazolam, and their major metabolites in human blood using LC-MS/MS [25], with the linear concentration ranges from 3.5 to 700 ng/mL for morphine and its metabolites. Clavijo et al determined morphine and its active metabolites M3G and M6G in human plasma and dried blood spots with a linear range of 0.25-100 ng/mL for morphine and M3G, and 1ß100 ng/mL for M6G [26].…”

Section: Discussionmentioning

confidence: 99%

“…One cycle of analysis of four compounds including positive ion and anion mode was 13 min; the retention time for morphine and its metabolites determination is only 1.8 min under positive ion mode. The mass spectrometer was modulated to own the anion and positive ion mode by using AJS ESI ion source under the following general conditions: capillary voltage: 5 kV for gemfibrozil and M6G-d3 (IS), 25 kV for M3G and M6G, and 30 kV for morphine; nebulization pressure: 45 psi; temperature of drying gas: 350ЊC; drying gas flow: 8 L/min; sheath gas temperature: 350ЊC; sheath gas flow: 11 L/min; cell accelerator voltage: 3 V for gemfibrozil and 4 V for morphine, M3G, M6G, and M6G-d3 (IS); collision energy: 5 eV for gemfibrozil and M6G-d3 (IS), 25 …”

Section: Uhplc-ms/ms Methodsmentioning

confidence: 99%

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Simultaneous analysis of gemfibrozil, morphine, and its two active metabolites in different mouse brain structures using solid‐phase extraction with ultra‐high performance liquid chromatography and tandem mass spectrometry with a deuterated internal standard

Yang

Wang

et al. 2016

J of Separation Science

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Simultaneous analysis of gemfibrozil, morphine, and its two active metabolites in different mouse brain structures using solid-phase extraction with ultra-high performance liquid chromatography and tandem mass spectrometry with a deuterated internal standard A rapid and sensitive bioassay was established and validated to simultaneously determine gemfibrozil, morphine, morphine-3␤-glucuronide, and morphine-6␤-glucuronide in mouse cerebrum, epencephalon, and hippocampus based on ultra-high performance liquid chromatography and tandem mass spectrometry. The deuterated internal standard, M6G-d3, was mixed with the prepared samples at 10 ng/mL as the final concentration. The samples were transferred into the C 18 solid-phase extraction columns with gradient elution for solid-phase extraction. The mobile phase consisted of methanol and 0.05% formic acid (pH 3. and M6G with correlation coefficients >0.993. The lower limit of quantitation for all four analytes was 0.05 ng/mL, relative standard deviation of intra-and interday precision was less than 10.5%, and the relative error of accuracy was from −8.2 to 8.3% at low, medium, and high concentrations for all the analytes. In conclusion, gemfibrozil can influence the morphine antinociception after coronary heart disease induced chronic angina by the change in one of morphine metabolites', M3G, distribution in mouse brain.

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Section: Discussionmentioning

confidence: 99%

Section: Uhplc-ms/ms Methodsmentioning

confidence: 99%

Simultaneous analysis of gemfibrozil, morphine, and its two active metabolites in different mouse brain structures using solid‐phase extraction with ultra‐high performance liquid chromatography and tandem mass spectrometry with a deuterated internal standard

Yang

Wang

et al. 2016

J of Separation Science

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“…Evidence-based practices such as use of sedation protocols [52], allowing lighter sedation with daily interruptions [52][53][54] and minimizing administration of paralytic agents, have all been shown to reduce morbidity in critically ill patients. However, these practices may not always be practical in a critically ill patient on ECLS.…”

Section: Sedatives and Analgesicsmentioning

confidence: 99%

“…This research will characterise the PK of 18 important drugs (Chapter 4) used during ECMO utilising validated ex vivo and large animal models of ECMO 52,53 ,efficient drug and metabolite assays 54 and a multi-national population PK collaboration 55 . This mechanistic data can be translated into clinical practice rapidly, facilitating optimal pharmacotherapy, minimizing the risk of therapeutic failure and the rise of antibiotic resistance from sub-therapeutic concentrations.…”

Section: Objectivesmentioning

confidence: 99%

“…In the setting of pneumonia or sepsis and severe cardiac dysfunction, where feasible, VV ECMO with inotropic support should be the initial perfusion strategy [53]. Septic myocardial depression may improve with management of the sepsis, improved oxygenation and normalisation of respiratory acidosis [54]. Peripheral femoral VA ECMO (Figure 2) may be considered a rescue option for these patients if …”

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confidence: 99%

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Sick patients, starved circuits and sticky drugs: understanding pharmacokinetics during extracorporeal membrane oxygenation to optimise drug dosing and improve patient outcomes

Shekar¹

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Extracorporeal membrane oxygenation (ECMO) is the final option for patients with acute severe cardiac and/or respiratory failure that is unresponsive to conventional management. ECMO plays a supportive role and its success relies on optimal drug therapy to reverse the underlying disease process and to prevent or treat complications.Vital drugs may be sequestered and/or degraded in the ECMO circuit resulting in altered pharmacokinetics (PK). This may be further complicated by the PK changes that occur in the presence of critical illness and may lead to therapeutic failure and/or drug toxicity.However, much of the currently available PK data is from neonates receiving ECMO and may not be extrapolated to adult patients given the developmental and physiologic differences. Equally, such PK alterations are complex and are challenging to investigate in a critically ill patient on ECMO. The aim of this research was to investigate each of the circuit, drug and critical illness factors affecting PK during ECMO in adult patients. A combination of linear and non-linear mixed effects modelling, compartmental and population methods and dosing simulations was utilised to characterise antibiotic, sedative and analgesic PK. The incremental research plan comprised of; (i) ex vivo experiments for drug stability testing in human blood;(ii) ex vivo drug disposition studies in ECMO circuits primed with fresh whole human blood;(iii) PK studies in healthy and critically ill ovine models of ECMO with appropriate non-ECMO controls and;(iv) an international multi-centre clinical population PK study in critically ill adults on ECMO.The introductory chapter (Chapter 1) outlines the origins of this research based on clinical observations, hypothesis generating preliminary data (Chapter 1.1), summarises the available extracorporeal life support therapies (Chapter 1.2) and provides a clinical context to PK alterations induced by ECMO (Chapter 1.3). This is followed by a literature review on PK alterations during ECMO (Chapter 2). Thus, an understanding of the clinical problem, available extracorporeal therapies, and identifying the gaps in literature (Chapter 3) facilitated the development of a comprehensive research plan (Chapter 4.1). Chapter 4.2 describes the methodology for the development of ex vivo and ovine models of ECMO. The protocol for the international multi-centre population PK study that aims to develop dosing guidelines for 18 key antibiotic, sedative and analgesic drugs is presented in Chapter 4.3.Ex vivo studies identified drug stability, lipophilicity (Chapter 5.1) and protein binding (Chapter 5.2) as the key drug factors determining their sequestration and /or degradation in iii ECMO circuits. An increase in peripheral volume of distribution (Vd) of the highly proteinbound, lipophilic drug midazolam was identified in both healthy and critically ill sheep on ECMO (Chapter 6.1) providing further in vivo evidence of circuit drug sequestration. PK of eight antibiotic drugs that exhibited a wide range of lipophilici...

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Determination of chidamide in rat plasma by LC‐MS and its application to pharmacokinetics study

Wang

Chen

Wen

et al. 2013

Biomedical Chromatography

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A sensitive and selective liquid chromatography mass spectrometry method for determination of chidamide in rat plasma was developed. After addition of linezolid as internal standard, protein precipitation by acetonitrile-methanol (9:1, v/v) was used as sample preparation. Chromatographic separation was achieved on a Zorbax SB-C18 (2.1 × 150 mm, 5 µm) column with acetonitrile-0.1% formic acid as mobile phase with gradient elution. An electrospray ionization source was applied and operated in positive ion mode; selective ion monitoring mode was used for quantification using target fragment ions m/z 391.5 for chidamide and m/z 338.5 for the IS. Calibration plots were linear over the range of 10-2000 ng/mL for chidamide in rat plasma. The lower limit of quantification for chidamide was 10 ng/mL. The mean recovery of chidamide in plasma was in the range of 86.6-92.1%. The coefficients of variation of intra-day and inter-day precision were both <12%. This method is simple and sensitive and was applied successfully in a pharmacokinetic study of chidamide to rats.

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High-throughput assay for simultaneous quantification of the plasma concentrations of morphine, fentanyl, midazolam and their major metabolites using automated SPE coupled to LC–MS/MS

Cited by 52 publications

References 25 publications

Simultaneous analysis of gemfibrozil, morphine, and its two active metabolites in different mouse brain structures using solid‐phase extraction with ultra‐high performance liquid chromatography and tandem mass spectrometry with a deuterated internal standard

Simultaneous analysis of gemfibrozil, morphine, and its two active metabolites in different mouse brain structures using solid‐phase extraction with ultra‐high performance liquid chromatography and tandem mass spectrometry with a deuterated internal standard

Sick patients, starved circuits and sticky drugs: understanding pharmacokinetics during extracorporeal membrane oxygenation to optimise drug dosing and improve patient outcomes

Determination of chidamide in rat plasma by LC‐MS and its application to pharmacokinetics study

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