A new LC-MS/MS confirmation method for the determination of 17 drugs of abuse in oral fluid and its application to real samples

Bassotti, Elisa; Merone, Giuseppe Maria; DʼUrso, Annachiara; Savini, Fabio; Locatelli, Marcello; Tartaglia, Angela; Dossetto, Paolo; D’Ovidio, Cristian; Grazia, Ugo de

doi:10.1016/j.forsciint.2020.110330

Cited by 33 publications

(29 citation statements)

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“…Perhaps the best advantage of saliva sampling is that it allows a very simple, specific, and sensitive test for monitoring ASMs free fraction, given the current availability of clinical LC-MS/MS techniques in TDM laboratories. In most cases, it is possible to prepare samples with a very simple “dilute and shot” method, avoiding concentration and precipitation steps while injecting a diluted saliva sample without affecting method performances [ 110 ]. Moreover, the sensitivity of LC-MS/MS also allows the examination of samples based on a dried saliva spot (DSS).…”

Section: Saliva As An Alternative Fluid For Measuring the Antiseizure Medications Free Fractionmentioning

confidence: 99%

“…CBZ has a half-life varying between 8 to 20 h in patients on chronic therapy and may be greater after a single dose due to metabolic autoinduction, whereas the half-life of the active metabolite CBZ-E is around 34 h. CBZ and CBZ-E are both protein-bound with different percentages: 75% for CBZ and 50–60% for CBZ-E [ 110 ]. Concentrations of CBZ and CBZ-E in saliva are significantly correlated with both serum total (r2 = 0.84–0.99 and r2 = 0.76–0.88, respectively) and serum-free concentrations (r2 = 0.91–0.99 and r2 = 0.75–0.98, respectively).…”

Section: Saliva As An Alternative Fluid For Measuring the Antiseizure Medications Free Fractionmentioning

confidence: 99%

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The Effect of Plasma Protein Binding on the Therapeutic Monitoring of Antiseizure Medications

et al. 2021

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Epilepsy is a widely diffused neurological disorder including a heterogeneous range of syndromes with different aetiology, severity and prognosis. Pharmacological treatments are based on the use, either in mono- or in polytherapy, of antiseizure medications (ASMs), which act at different synaptic levels, generally modifying the excitatory and/or inhibitory response through different action mechanisms. To reduce the risk of adverse effects and drug interactions, ASMs levels should be closely evaluated in biological fluids performing an appropriate Therapeutic Drug Monitoring (TDM). However, many decisions in TDM are based on the determination of the total drug concentration although measurement of the free fraction, which is not bound to plasma proteins, is becoming of ever-increasing importance since it correlates better with pharmacological and toxicological effects. Aim of this work has been to review methodological aspects concerning the evaluation of the free plasmatic fraction of some ASMs, focusing on the effect and the clinical significance that drug-protein binding has in the case of widely used drugs such as valproic acid, phenytoin, perampanel and carbamazepine. Although several validated methodologies are currently available which are effective in separating and quantifying the different forms of a drug, prospective validation studies are undoubtedly needed to better correlate, in real-world clinical contexts, pharmacokinetic monitoring to clinical outcomes.

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Section: Saliva As An Alternative Fluid For Measuring the Antiseizure Medications Free Fractionmentioning

confidence: 99%

Section: Saliva As An Alternative Fluid For Measuring the Antiseizure Medications Free Fractionmentioning

confidence: 99%

The Effect of Plasma Protein Binding on the Therapeutic Monitoring of Antiseizure Medications

et al. 2021

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“…In many forensic contexts, oral fluid is analysed with screening methods. The semiquantitative results obtained must be validated by confirmatory techniques, such as liquid chromatography combined with mass spectrometry [18]. Oral fluids (OF) have been recently introduced as a biological matrix useful for roadside testing to determine illicit drug use because the time course of drugs in oral fluid may resemble that of plasma.…”

Section: Analytical Techniquesmentioning

confidence: 99%

Salivary Analysis for Medico-Legal and Forensic Toxicological Purposes

Scendoni¹

2021

Forensic Analysis - Scientific and Medical Techniques and Evidence Under the Microscope

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Saliva testing has attracted great interest in the forensic scientific landscape recently, especially among institutions or legal authorities interested in determining drug concentrations (for application in the workplace, drug driving, legal issues associated with drug testing, and pharmacokinetics of selected drugs). Indeed, it has been established that oral fluid is an adequate alternative biological matrix to blood for the determination of xenobiotics and/or drugs of abuse and/or metabolites both in living and deceased individuals. The concentration of a detectable substance in saliva is generally proportional to the free fraction of the drug present in plasma; this measurement therefore makes it possible to correlate the concentration of the substance and its pharmacological effects on the individual. The purpose of this chapter is to examine the main analytical techniques developed thus far in saliva drug testing, from screening to confirmatory analysis, taking into account the interpretation of cut-off levels. Both well-defined and potentially problematic issues are highlighted from medico-legal and toxicological perspectives.

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“…Human OF can be produced at a rate up to 6 mL min À1 , 12 making multisampling possible for repetitive or periodical analysis, such as pharmacodynamics studies. Besides, the concentration of drugs in OF and plasma are usually correlated, 13,14 which is of paramount importance as the plasma concentration denes the actual therapeutic or toxic effects. However, OF analysis faces the same challenges observed for conventional biosamples, namely: the low concentration of the analytes and the high presence of interferents.…”

Section: Introductionmentioning

confidence: 99%

Polydopamine coated hypodermic needles as a microextraction device for the determination of tricyclic antidepressants in oral fluid by direct infusion MS/MS

et al. 2021

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A new LC-MS/MS confirmation method for the determination of 17 drugs of abuse in oral fluid and its application to real samples

Cited by 33 publications

References 11 publications

The Effect of Plasma Protein Binding on the Therapeutic Monitoring of Antiseizure Medications

The Effect of Plasma Protein Binding on the Therapeutic Monitoring of Antiseizure Medications

Salivary Analysis for Medico-Legal and Forensic Toxicological Purposes

Polydopamine coated hypodermic needles as a microextraction device for the determination of tricyclic antidepressants in oral fluid by direct infusion MS/MS

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