A simple, sensitive and robust method for simultaneous determination of antiepileptic drugs (gabapentin, pregabalin and vigabatrin) in human serum using GC-MS was developed and validated for clinical toxicology purposes. This method employs an emerging class of derivatization agents - alkyl chloroformates allowing the efficient and rapid derivatization of both the amino and carboxylic groups of the tested antiepileptic drugs within seconds. The derivatization protocol was optimized using the Design of Experiment statistical methodology, and the entire sample preparation requires less than 5 min. Linear calibration curves were obtained in the concentration range from 0.5 to 50.0 mg/L, with adequate accuracy (97.9-109.3%) and precision (<12.1%). The method was successfully applied to quantification of selected γ-aminobutyric acid analogs in the serum of patients in both therapeutic and toxic concentration ranges.

• MeSH
• Amines analysis   blood   MeSH
• Anticonvulsants analysis   blood   MeSH
• Computer-Aided Design MeSH
• Formates chemistry   MeSH
• gamma-Aminobutyric Acid analogs & derivatives   analysis   blood   MeSH
• Gabapentin MeSH
• Calibration MeSH
• Cyclohexanecarboxylic Acids analysis   blood   MeSH
• Humans MeSH
• Gas Chromatography-Mass Spectrometry MeSH
• Pregabalin analysis   blood   MeSH
• Vigabatrin analysis   blood   MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Names of Substances
• Amines MeSH
• Anticonvulsants MeSH
• Formates MeSH
• gamma-Aminobutyric Acid MeSH
• Gabapentin MeSH
• hexylchloroformate MeSH Browser
• Cyclohexanecarboxylic Acids MeSH
• Pregabalin MeSH
• Vigabatrin MeSH

BACKGROUND: There are limited data on the effects of GBP on bone and no data for PGB. Some data suggest that there is a significant influence of sex hormone balance on the susceptibility of bone to antiepileptic drug-induced bone loss. METHODS: Forty-eight male Wistar rats were divided into six groups that were subjected to two surgeries, sham (noORX) or real orchidectomy (ORX), and were fed three diets, a SLD, a SLD enriched with GBP or a SLD enriched with PGB. Dual energy X-ray absorptiometry was used to measure the bone mineral density. The concentrations of bone turnover markers were assayed. The femurs were biomechanically tested. RESULTS: Significant reductions in bone mineral density, weight and biomechanical strength were observed in ORX animals. GBP or PGB exposure did not cause significant alterations in bone mineral density or biomechanical strength. No changes in bone turnover markers were observed, except for RANKL. A significant increase was found in the ORX GBP and ORX PGB groups. Within the orchidectomized animal group, RANKL levels were significantly higher in the ORX PGB group than in the ORX GBP group. CONCLUSIONS: Because neither GBP nor PGB affected bone mineral density or mechanical bone strength, both of these antiepileptic drugs could be considered drugs with lower risks to bone health. A shift in RANKL levels indicates that the effects of GBP and PGB on osteoclast activity may be dependent on the hormonal status of animals.

• Keywords
• Amino-terminal propeptide of procollagen type I, Bone alkaline phosphatase, Bone mineral density, Receptor activator of nuclear factor-kappa B ligand,
• MeSH
• Absorptiometry, Photon methods   MeSH
• Alkaline Phosphatase metabolism   MeSH
• Anticonvulsants pharmacology   MeSH
• Biomechanical Phenomena drug effects   MeSH
• Femur drug effects   metabolism   MeSH
• Gabapentin pharmacology   MeSH
• Bone Density drug effects   MeSH
• Rats MeSH
• Orchiectomy methods   MeSH
• Osteoprotegerin metabolism   MeSH
• Rats, Wistar MeSH
• Pregabalin pharmacology   MeSH
• Prospective Studies MeSH
• Bone Remodeling drug effects   MeSH
• Animals MeSH
• Check Tag
• Rats MeSH
• Male MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Names of Substances
• Alkaline Phosphatase MeSH
• Anticonvulsants MeSH
• Gabapentin MeSH
• Osteoprotegerin MeSH
• Pregabalin MeSH

PURPOSE: Behavioral side effects of antiepileptic drugs (AEDs) are common including both positive and negative effects on mood, anxiety, depression, and psychosis. We aimed to evaluate behavioral patterns in rats after administration of lamotrigine, levetiracetam, phenytoin, topiramate, carbamazepine, gabapentin, pregabalin, and zonisamide. METHODS: The open-field test was performed and locomotion, rearing, grooming, central latency and defecation were recorded over a 5min interval for each rat (8 rats in each group receiving AED and 16 controls). Kruskal-Wallis nonparametric test or ANOVA were used to assess differences among the groups. RESULTS: The experimental groups did not differ in latency to enter the center compartment, neither in the decline of locomotor activity in the 1st and the 5th minute of the observation, nor in number of rears. Significant differences among groups were observed in the total number of lines crossed, grooming, as well in the number of fecal pellets. Locomotor activity was significantly increased in lamotrigine, if compared with gabapentin and pregabalin (ANOVA; p <0.05). Rats exposed to topiramate displayed a significantly increased number of grooming (when compared to pregabalin: p<0.01). Defecation (the number of fecal pellets) significantly increased in the gabapentin and carbamazepine group. CONCLUSION: There are significant differences between AEDs in terms of their behavioral profile. It is of great importance to evaluate these effects in clinical practice to bring more clear insight into these positive or negative side effects of AEDs.

• Keywords
• Antiepileptic drugs, Anxiety, Behavior, Open-field test,
• MeSH
• Affect drug effects   MeSH
• Anticonvulsants blood   pharmacology   MeSH
• Feces MeSH
• Rats MeSH
• Locomotion drug effects   MeSH
• Statistics, Nonparametric MeSH
• Exploratory Behavior drug effects   MeSH
• Grooming drug effects   MeSH
• Rats, Wistar MeSH
• Reaction Time drug effects   MeSH
• Body Weight drug effects   MeSH
• Dose-Response Relationship, Drug MeSH
• Animals MeSH
• Check Tag
• Rats MeSH
• Male MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Names of Substances
• Anticonvulsants MeSH

Electrophoretic stacking is developed for sensitive determination of three zwitterionic antiepileptics, namely vigabatrin, pregabalin and gabapentin, in human serum. CE separation is performed in a 25 μm fused silica capillary covalently coated with the copolymer of acrylamide with 5% content of permanently charged 3-acrylamidopropyl trimethylammonium chloride (PAMAPTAC). In background electrolyte of 500 mM acetic acid, the 5% PAMAPTAC generates an anodic electro-osmotic flow with a magnitude of (-18.6 ± 0.5) · 10-9 m2V-1s-1, which acts against the direction of the electrophoretic migration of the analytes. A sample of the antiepileptic prepared in a 25% v/v infusion solution and 75% v/v acetonitrile is injected into the capillary in a large volume attaining a zone length of up to 270 mm. After turning on the separation voltage, the antiepileptics are isotachophoretically focussed behind the zone of Na+ ions with a sensitivity enhancement factor of 78. For the clinical determination of antiepileptics, the human serum is diluted with acetonitrile in a ratio of 1:3 v/v and a zone with a length of 90 mm is injected into the capillary. The method is linear in the 0.025-2.5 μg/mL concentration range; the attained limit of quantification is in the range 18.3-22.8 nmol/L; the within-day precision for the migration time is 0.8-1.2% and for the peak area 1.5-2.4%.

• Keywords
• Antiepileptic, Capillary electrophoresis, Coating, Contactless conductivity detection, Sample pretreatment, Serum, Stacking,
• MeSH
• Anticonvulsants * MeSH
• Chlorides * MeSH
• Electrophoresis, Capillary MeSH
• Humans MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Names of Substances
• Anticonvulsants * MeSH
• Chlorides * MeSH