Gabapentin, Pregabalin and Vigabatrin Quantification in Human Serum by GC–MS After Hexyl Chloroformate Derivatization

Hložek, Tomáš; Bursová, Miroslava; Coufal, Pavel; Čabala, Radomír

doi:10.1093/jat/bkw070

Cited by 10 publications

(15 citation statements)

References 23 publications

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“…Before analyzing real samples, several derivatisation procedures were evaluated on standard PGB solutions. To the best of our knowledge, scant literature is available dealing with the GC–MS determination of PGB . In these contributions, chloroformate derivatives of PGB are suggested as the elective choice for the analysis of drug in pharmaceutical formulations and biological matrices.…”

Section: Resultsmentioning

confidence: 99%

GC‐MS/MS detects potential pregabalin abuse in susceptible subjects’ hair

Ianni

Aroni

Gili

et al. 2018

Drug Testing and Analysis

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Pregabalin, a GABA analogue, binds to the alpha 2 delta subunit of voltage-dependent calcium channels. It is recognised as efficacious in pathologies such as epilepsy, neuropathic pain, and anxiety disorders. Since pregabalin prescriptions have increased worldwide, reports of its abuse have been accumulating, mainly in patients with opioid abuse disorders. The present study investigated potential pregabalin abuse by means of hair analysis, a matrix that provides valuable retrospective information. Half of the pool of 280 susceptible patients had been occasional drug users and were being monitored for driving licence renewals. The other 140 patients had a history of opiate dependency and were monitored to assess compliance with methadone therapy. In view of determining pregabalin in hair samples, it was extracted in methanol, successfully derivatised to give the ethyl chloroformate derivative, and finally pregabalin was analysed by gas chromatography-tandem mass spectrometry. Selectivity, linearity, limit of detection, limit of quantification, recovery, intra- and inter-day precision, and accuracy of the quantification procedure were appraised. Pregabalin limits of detection and quantification were 30 pg/mg and 50 pg/mg, respectively. We found 10.7% of hair samples from methadone patients and 4.29% from occasional drug users were positive to pregabalin without medical prescription. The mean pregabalin concentration in hair was higher than in consumers with medical indications (1.45 ng/mg vs 0.74 ng/mg). These results suggest that pregabalin possesses a significant abuse potential particularly among individuals attending opiate dependence services and that pregabalin abuse is a serious emerging issue, which should be carefully monitored.

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Section: Resultsmentioning

confidence: 99%

GC‐MS/MS detects potential pregabalin abuse in susceptible subjects’ hair

Ianni

Aroni

Gili

et al. 2018

Drug Testing and Analysis

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“…Applications of DOE in optimizing the derivatization method has been limited to GC-MS analysis. 17,18 The present study is the first application for chiral derivatization -LC-MS/MS analysis.…”

Section: Introductionmentioning

confidence: 94%

Introducing an Experimental Design Approach for Efficient Optimization of Chiral Derivatization Conditions for d- and l-Glyceric Acids

et al. 2019

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A sensitive analytical method was developed for individual analyses of D-and L-glyceric acids by chiral derivatization liquid chromatography-tandem mass spectrometry. To elucidate rapid and efficient optimization for derivatization we newly introduced a concept of design of experiments (DOE). The optimization of major 5 factors in the derivatization could be predicted with only 28 measurements. By applying DOE to optimization, the yields of desired derivatives increased five-fold against before optimization.

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“…An initial clinical study has demonstrated the use of pregabalin as an adjuvant to labor pain relief associated with late termination of pregnancy [84]. Plasma drug concentrations can be determined via HPLC [85], LC–MS/MS [85, 86], GC–MS [87], or a fluorometric method [88]. …”

Section: Newer Antiepileptic Drugsmentioning

confidence: 99%

An Updated Overview on Therapeutic Drug Monitoring of Recent Antiepileptic Drugs

2016

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Given the distinctive characteristics of both epilepsy and antiepileptic drugs (AEDs), therapeutic drug monitoring (TDM) can make a significant contribution to the field of epilepsy. The measurement and interpretation of serum drug concentrations can be of benefit in the treatment of uncontrollable seizures and in cases of clinical toxicity; it can aid in the individualization of therapy and in adjusting for variable or nonlinear pharmacokinetics; and can be useful in special populations such as pregnancy. This review examines the potential for TDM of newer AEDs such as eslicarbazepine acetate, felbamate, gabapentin, lacosamide, lamotrigine, levetiracetam, perampanel, pregabalin, rufinamide, retigabine, stiripentol, tiagabine, topiramate, vigabatrin, and zonisamide. We describe the relationships between serum drug concentration, clinical effect, and adverse drug reactions for each AED as well as the different analytical methods used for serum drug quantification. We discuss retrospective studies and prospective data on the serum drug concentration–efficacy of these drugs and present the pharmacokinetic parameters, oral bioavailability, reference concentration range, and active metabolites of newer AEDs. Limited data are available for recent AEDs, and we discuss the connection between drug concentrations in terms of clinical efficacy and nonresponse. Although we do not propose routine TDM, serum drug measurement can play a beneficial role in patient management and treatment individualization. Standardized studies designed to assess, in particular, concentration–efficacy–toxicity relationships for recent AEDs are urgently required.

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Gabapentin, Pregabalin and Vigabatrin Quantification in Human Serum by GC–MS After Hexyl Chloroformate Derivatization

Cited by 10 publications

References 23 publications

GC‐MS/MS detects potential pregabalin abuse in susceptible subjects’ hair

GC‐MS/MS detects potential pregabalin abuse in susceptible subjects’ hair

Introducing an Experimental Design Approach for Efficient Optimization of Chiral Derivatization Conditions for d- and l-Glyceric Acids

An Updated Overview on Therapeutic Drug Monitoring of Recent Antiepileptic Drugs

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