Liquid chromatography–tandem mass spectrometry determination of baclofen in various biological samples and application to a pharmacokinetic study

Kim, So Yeon; Shin, Soyoung; Shin, Jeong Cheol; Choi, Jin Woong; Seo, Won Sik; Park, Gi-Young; Kwon, Dong Rak; Yoo, Sun Dong; Lee, Ah-Ram; Joo, Sang Hoon; Min, Byung Sun; Yoo, Won Young; Shin, Beom Soo

doi:10.1016/j.jchromb.2013.08.030

Cited by 15 publications

(12 citation statements)

References 33 publications

(33 reference statements)

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“…The PK characteristics of baclofen observed in this study were well comparable with the previous reports [19, 25–27]. …”

Section: Discussionsupporting

confidence: 92%

“…Baclofen concentrations were determined by the LC/MS/MS assay as reported previously [19]. Briefly, the internal standard (IS) working solution (4 μ L of 200 ng/mL IS solution for plasma samples and 8 μ L of 200 ng/mL IS solution for urine samples) and diluted perchloric acid (4 μ L of 2 M solution for plasma samples and 40 μ L 0.2 M solution for urine samples) were added to 20 μ L of each sample as precipitation solvent.…”

Section: Methodsmentioning

confidence: 99%

“…The peak serum concentration ( C max⁡ ) and the time to reach C max⁡ ( T max⁡ ) were read directly from the observations. The absolute bioavailability ( F ) of baclofen after oral dosing was calculated as F = (Dose iv · AUC oral )/(Dose oral · AUC iv ), where AUC iv was obtained from the previous study [19]. …”

Section: Methodsmentioning

confidence: 99%

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Pharmacokinetic Alteration of Baclofen by Multiple Oral Administration of Herbal Medicines in Rats

Kim

Park

Shin

et al. 2014

Evidence-Based Complementary and Alternative Medicine

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The potential pharmacokinetic (PK) interaction of conventional western drug, baclofen, and oriental medications Oyaksungisan (OY) and Achyranthes bidentata radix (AB) extract for the treatment of spasticity has been evaluated. Rats were pretreated with distilled water (DW), OY, or AB extract by oral administration every day for 7 days. After 10 min of the final dose of DW or each herbal medication, baclofen (1 mg/kg) was given by oral administration and plasma concentrations of baclofen were determined by LC/MS/MS. The plasma baclofen concentration-time profiles were then analyzed by noncompartmental analysis and a population PK model was developed. Baclofen was rapidly absorbed, showed biexponential decline with elimination half-life of 3.42–4.10 hr, and mostly excreted into urine. The PK of baclofen was not affected by AB extract pretreatment. However, significantly lower maximum plasma concentration (C max) and longer time to reach C max (T max) were observed in OY pretreated rats without changes in the area under the curve (AUC) and the fraction excreted into urine (F urine). The absorption rate (K a) of baclofen was significantly decreased in OY pretreated rats. These data suggested that repeated doses of OY might delay the absorption of baclofen without changes in extent of absorption, which needs further evaluation for clinical significance.

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“…The PK characteristics of baclofen observed in this study were well comparable with the previous reports [19, 25–27]. …”

Section: Discussionsupporting

confidence: 92%

Section: Methodsmentioning

confidence: 99%

See 1 more Smart Citation

Pharmacokinetic Alteration of Baclofen by Multiple Oral Administration of Herbal Medicines in Rats

Kim

Park

Shin

et al. 2014

Evidence-Based Complementary and Alternative Medicine

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“…Baclofen had an inhibitory effect on pup retrieval for approximately 8 h. Because of the low proportion of saline-treated females that retrieved pups during the first 3 h, the effect was significant only between 4 and 8 h postinjection. The duration of the baclofen effect is in agreement with pharmacokinetic studies of this drug, showing a half-life of 4-6 h after systemic administration (34). Thus, pup retrieval was enhanced as long as any of the GABA receptors was blocked, whereas it was reduced as long as the GABA B receptor was stimulated.…”

Section: Discussionsupporting

confidence: 84%

GABA Receptors in the Medial Preoptic Area Modulate the Onset of Oestradiol‐Induced Maternal Behaviour in Hysterectomised‐Ovariectomised, Pregnant Rats

Gómora‐Arrati

Domínguez

Ågmo

2016

J Neuroendocrinology

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We studied the participation of GABA neurotransmission in the medial preoptic area (mPOA) with respect to the onset of the pup retrieval response and nest building. Pregnant female rats were implanted with bilateral cannulae in the mPOA on day 12 of pregnancy and, on day 16, the females were hysterectomised and ovariectomised and given 200 μg/kg of oestradiol benzoate. Two days later, the females received one of the following intracerebral drug treatments: GABA agonist baclofen (200 ng); GABA antagonist phaclofen (1 μg); GABA antagonist bicuculline (60 ng); or physiological saline. Five minutes after intracerebral infusion, three foster pups were introduced into the females' home cage. The subjects were observed for pup grouping (retrieval) during 15 min, after which the pups were left with the female. During the next 12 h, an observation was made every 1 h to determine whether the pups had been grouped (retrieved) or not. The GABA agonist baclofen reduced the proportion of females retrieving pups from 4 to 8 h following pup introduction. By contrast, both the GABA antagonist bicuculline and the GABA antagonist phaclofen enhanced the proportion of females retrieving pups during the first 3 h of observation. The latency to pup retrieval in subjects treated with the GABA agonist baclofen was significantly longer than that in subjects given any of the antagonists. All females built a nest but baclofen reduced nest quality. These data show that activation of GABA receptors in the mPOA has an inhibitory effect on basic maternal behaviours, whereas blockade of either the GABA or GABA receptor facilitates pup retrieval. It is possible that reduced GABAergic tone in the mPOA is a key element in the initiation of maternal behaviours in postparturient rats.

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“…In the literature, several studies have described the determination of baclofen in biological fluids by various methods such as capillary electrophoresis, gas chromatography and liquid chromatography with UV, fluorescence after derivatization or tandem mass spectrometry (Cao & Li, ; Desiderio et al, ; Flärdh & Jacobson, ; Goda, Murayama, Fujimaki, & Sudo, ; Kim et al, ; Millerioux, Brault, Gualano, & Mignot, ; Nahar et al, ). All of the methods described have been validated only for the quantification of baclofen in different biological matrices and require complex sample preparation procedures such as derivatization, liquid–liquid extraction, solid‐phase extraction or ion pair extraction.…”

Section: Introductionmentioning

confidence: 99%

Liquid chromatography high resolution mass spectrometry for the determination of baclofen and its metabolites in plasma: Application to therapeutic drug monitoring

Labat

Goncalves

Marques

et al. 2017

Biomedical Chromatography

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Baclofen is used to manage alcohol dependence. This study describes a simple method using liquid chromatography coupled to high-resolution mass spectrometry (LC-HR-MS) developed in plasma samples. This method was optimized to allow quantification of baclofen and determination of metabolic ratio of its metabolites, an oxidative deaminated metabolite of baclofen (M1) and its glucuronide form (M2). The LC-HR-MS method on Exactive® apparatus is a newly developed method with all the advantages of high resolution in full-scan mode for the quantification of baclofen and detection of its metabolites in plasma. The present assay provides a protein precipitation method starting with 100 μL plasma giving a wide polynomial dynamic range (R > 0.999) between 10 and 2000 ng/mL and a lower limit of quantitation of 3 ng/mL for baclofen. Intra- and inter-day precisions were <8.1% and accuracies were between 91.2 and 103.3% for baclofen. No matrix effect was observed. The assay was successfully applied to 36 patients following baclofen administration. Plasma concentrations of baclofen were determined between 12.2 and 1399.9 ng/mL and metabolic ratios were estimated between 0.4 and 81.8% for M1 metabolite and on the order of 0.3% for M2 in two samples.

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Liquid chromatography–tandem mass spectrometry determination of baclofen in various biological samples and application to a pharmacokinetic study

Cited by 15 publications

References 33 publications

Pharmacokinetic Alteration of Baclofen by Multiple Oral Administration of Herbal Medicines in Rats

Pharmacokinetic Alteration of Baclofen by Multiple Oral Administration of Herbal Medicines in Rats

GABA Receptors in the Medial Preoptic Area Modulate the Onset of Oestradiol‐Induced Maternal Behaviour in Hysterectomised‐Ovariectomised, Pregnant Rats

Liquid chromatography high resolution mass spectrometry for the determination of baclofen and its metabolites in plasma: Application to therapeutic drug monitoring

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