OBJECTIVE: To determine transplacental passage of topiramate and its transport to colostrum, mature maternal milk and breastfed infants, we examined data from 27 women treated with topiramate from 2004 to 2020. METHODS: In this cohort study, maternal serum, umbilical cord serum, milk and infant serum levels were measured by gas chromatography in the delivery subgroup, the colostrum subgroup (3-4 days postpartum) and the mature milk subgroup (7-30 days postpartum). Paired umbilical cord serum, maternal serum, breastfed infant serum, and milk levels were used to assess the ratios of umbilical cord/maternal serum, milk/maternal serum and infant/maternal serum levels. RESULTS: Topiramate levels varied from 1.0 to 7.1 mg/L in maternal serum and from 0.8 to 6.2 mg/L in umbilical cord serum, and the mean umbilical cord/maternal serum ratio was 0.93 ± 0.11. At 3-4 days after delivery, topiramate concentrations were 1.4-8.4 mg/L in maternal serum, 1.5-8.6 mg/L in milk and 0.3-4.4 mg/L in infant serum. The mean milk/maternal serum ratio was 0.99 ± 0.45, and the mean infant/maternal serum ratio was 0.25 ± 0.15. At 7-30 days after delivery, maternal serum levels varied from 1.9 to 9.7 mg/L, milk levels ranged from 2.3 to 10.6 mg/L and infant serum levels ranged from 0.3 to 6.5 mg/L. The mean milk/maternal serum ratio was 1.07 ± 0.31, and the mean infant/maternal serum ratio was 0.51 ± 0.27. CONCLUSIONS: We extended information about free transplacental passage of topiramate and its extensive transport to maternal milk with lower serum concentrations in breastfed infants in the largest group of patients ever reported to our knowledge. DATA AVAILABILITY STATEMENT: Authors declare that take full responsibility for the data, the analyses and interpretation, and the conduct of the research; that they have full access to all of the data; and that they have the right to publish all data. Authors were not participations in industry-sponsored research and corporate activities for evaluation of a manuscript.

• Klíčová slova
• Breastfeeding, Delivery, Therapeutic drug monitoring, Topiramate,
• MeSH
• antikonvulziva aplikace a dávkování   analýza   metabolismus   MeSH
• dospělí MeSH
• kohortové studie MeSH
• kojení MeSH
• laktace účinky léků   metabolismus   MeSH
• lidé MeSH
• mateřské mléko účinky léků   metabolismus   MeSH
• mladý dospělý MeSH
• monitorování léčiv metody   MeSH
• novorozenec MeSH
• topiramat aplikace a dávkování   analýza   metabolismus   MeSH
• vedení porodu metody   MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• novorozenec MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• antikonvulziva MeSH
• topiramat MeSH

The increase in the production and consumption of pharmaceuticals increases their presence in the global environment, which may result in direct threats to living organisms. For this reason, there is a need for new methods to analyze drugs in environmental samples. Here, a new procedure for separating and determining selected drugs (diclofenac, ibuprofen, and carbamazepine) from bottom sediment and water samples was developed. Drugs were determined by ultra-high performance liquid chromatography coupled with an ultraviolet detector (UHPLC-UV). In this work, a universal and single-step sample treatment, based on supramolecular solvents (SUPRAS), was proposed to isolate selected anticonvulsants and nonsteroidal anti-inflammatory drugs (NSAIDs) from sediment samples. The following parameters were experimentally selected: composition of the supramolecular solvent (composition THF:H2O (v/v), amount of decanoic acid), volume of extractant, sample mass, extraction time, centrifugation time, and centrifugation speed. Finally, the developed procedure was validated. A Speedisk procedure was also developed to extract selected drugs from water samples. The recovery of analytes using the SUPRAS procedure was in the range of 88.8-115%, while the recoveries of the Speedisk solid-phase extraction procedure ranged from 81.0-106%. The effectiveness of the sorption of the tested drugs by sediment was also examined.

• Klíčová slova
• Speedisk, liquid chromatography, micropollutants, supramolecular solvent-based microextraction,
• MeSH
• antiflogistika nesteroidní analýza   izolace a purifikace   MeSH
• antikonvulziva analýza   izolace a purifikace   MeSH
• chemické látky znečišťující vodu analýza   izolace a purifikace   MeSH
• léčivé přípravky analýza   izolace a purifikace   MeSH
• limita detekce MeSH
• mikroextrakce kapalné fáze metody   MeSH
• rozpouštědla chemie   MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• antiflogistika nesteroidní MeSH
• antikonvulziva MeSH
• chemické látky znečišťující vodu MeSH
• léčivé přípravky MeSH
• rozpouštědla MeSH

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
• aminy analýza   krev   MeSH
• antikonvulziva analýza   krev   MeSH
• design s pomocí počítače MeSH
• formiáty chemie   MeSH
• GABA analogy a deriváty   analýza   krev   MeSH
• gabapentin MeSH
• kalibrace MeSH
• kyseliny cyklohexankarboxylové analýza   krev   MeSH
• lidé MeSH
• plynová chromatografie s hmotnostně spektrometrickou detekcí MeSH
• pregabalin analýza   krev   MeSH
• vigabatrin analýza   krev   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• aminy MeSH
• antikonvulziva MeSH
• formiáty MeSH
• GABA MeSH
• gabapentin MeSH
• hexylchloroformate MeSH Prohlížeč
• kyseliny cyklohexankarboxylové MeSH
• pregabalin MeSH
• vigabatrin MeSH

The anticonvulsant drug carbamazepine is considered as an indicator of sewage water pollution: however, its uptake by plants and effect on metabolism have not been sufficiently documented, let alone its metabolite (10,11-epoxycarbamazepine). In a model system of sterile, hydroponically cultivated Zea mays (as C4 plant) and Helianthus annuus (as C3 plant), the uptake and effect of carbamazepine and 10,11-epoxycarbamazepine were studied in comparison with those of acetaminophen and ibuprofen. Ibuprofen and acetaminophen were effectively extracted from drug-supplemented media by both plants, while the uptake of more hydrophobic carbamazepine was much lower. On the other hand, the carbamazepine metabolite, 10,11-epoxycarbamazepine, was, unlike sunflower, willingly taken up by maize plants (after 96 h 88 % of the initial concentration) and effectively stored in maize tissues. In addition, the effect of the studied pharmaceuticals on the plant metabolism (enzymes of Hatch-Slack cycle, peroxidases) was followed. The activity of bound peroxidases, which could cause xylem vessel lignification and reduction of xenobiotic uptake, was at the level of control plants in maize leaves contrary to sunflower. Therefore, our results indicate that maize has the potential to remove 10,11-epoxycarbamazepine from contaminated soils.

• Klíčová slova
• 10,11-Epoxycarbamazepine, Acetaminophen, Carbamazepine, Ibuprofen, NADP-ME, PEPC, Peroxidases, Phytoremediation,
• MeSH
• antikonvulziva analýza   metabolismus   MeSH
• biodegradace MeSH
• Helianthus účinky léků   růst a vývoj   metabolismus   MeSH
• hydroponie MeSH
• karbamazepin analogy a deriváty   analýza   metabolismus   MeSH
• kukuřice setá účinky léků   růst a vývoj   metabolismus   MeSH
• látky znečišťující půdu analýza   metabolismus   MeSH
• listy rostlin účinky léků   růst a vývoj   metabolismus   MeSH
• vysokoúčinná kapalinová chromatografie MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Geografické názvy
• Česká republika MeSH
• Názvy látek
• antikonvulziva MeSH
• carbamazepine epoxide MeSH Prohlížeč
• karbamazepin MeSH
• látky znečišťující půdu MeSH

An HPLC procedure for the determination of lamotrigine (LAM) simultaneously with other antiepileptic drugs, primidone (PD), phenobarbital (PB), phenytoin (DPH), carbamazepine (CMZ), and two active metabolites 2-phenyl-2-ethyl-malonamide (PEMA) and 10,11-dihydro-10,11-epoxycarbamazepine (EPO) was developed and validated. The method involves an ordinary RP system and a liquid-liquid extraction. The mobile phase consisting of water/ACN/methanol/triethylamine in the ratio 72:23:5:0.1 with pH 7.0 was selected as the best one after the assays testing both pH and triethylamine contents. UV detection was carried out at a wavelength of 220 nm and the whole analysis took 15 min. The method was linear in the range of 0.5-25 mg/L for PEMA and LAM; 1.25-25 mg/L for PD and CMZ; 0.625-12.5 mg/L for EPO; 1.5-60 mg/L for PB; and 1.25-50 mg/L for DPH, respectively. Within-day CV% and between-day CV% were within 10%. The developed HPLC method can be used for routine therapeutic drug monitoring both in children and adults.

• MeSH
• antikonvulziva analýza   metabolismus   MeSH
• kalibrace MeSH
• koncentrace vodíkových iontů MeSH
• lidé MeSH
• vysokoúčinná kapalinová chromatografie metody   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• antikonvulziva MeSH

• MeSH
• antikonvulziva analýza   MeSH
• magnetická rezonanční spektroskopie MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• antikonvulziva MeSH