Influencing factors of phenobarbital treatment effect in rural epilepsy patients in Hubei Province / 公共卫生与预防医学

Objective To analyze the main factors influencing the management effect of rural epilepsy prevention and control projects in Hubei Province, and to provide reference for further improving the management effect. Methods According to the phenobarbital treatment and management plan of the rural epilepsy project, the target population was screened and reviewed, and patients who met the inclusion criteria were enrolled into the project management. Regular follow-up visits, free drug treatment, health education and other measures were carried out, and all relevant information was collected and integrated into the survey data. After the data was reviewed level by level, SPSS20.0 software was used for statistical analysis. Results From January 1, 2015 to December 31, 2020, among patients treated and managed with phenobarbital in 6 project counties, 1430 patients were treated and managed for more than 1 year, of whom 1119 (78.25%) had no seizures or had more than 75% reduction in the number of seizures during the observation period. Compared with other age groups, the age group of 65 years and above had the highest markedly effective/effective ratio (95.77%). From the point of follow-up, the markedly effective/effective ratio of 5 years and above was the highest (91.51%). Compared with those who received no treatment prior to enrollment and those who received regular treatment, the patients receiving informal treatment had the lowest markedly effective/effective ratio (82.43%). 1213 cases (84.83%) had good compliance during the observation period, of whom 1062 cases (87.55%) had a reduction in the number of seizures by more than 50% compared with that before treatment. Univariate analysis showed that the age of patients, the length of follow-up, the treatment status before enrollment, the average daily dose of phenobarbital and the compliance of patients all had an impact on the management effect, and the difference was statistically significant (P<0.05). Multivariate analysis showed that the markedly effective/effective rate of patients in the age group of 65 years and above was 6.749 times that of the younger age group. Receiving informal treatment prior to enrollment was a risk factor for difficult-to-control epilepsy. The markedly effective/effective rate of patients receiving informal treatment was 0.29 times that of patients never receiving treatment. Good compliance was a protective factor for epilepsy control, and the markedly effective/effective rate of patients with good compliance was 2.058 times that of patients with poor compliance. Conclusion The epilepsy prevention and management project in rural areas has a significant effect on seizure control. Early treatment, standardized treatment, and improvement of treatment compliance are effective ways to improve the management effect of epilepsy patients.

Hepatoprotective Activity of Aqueous Extract of Cashew Apple Cake (Anacardium occidentale L.) in Rats and Mice

Aims: The aqueous extract of cashew apple cakes, rich in molecules of pharmacological interest, could be used against many diseases. Thus, the aim of the present work is to evaluate its hepatoprotective activity in rats and mice. Methodology: Two batches of rats weighing between 200 and 300 grams, with five rats per batch, were pretreated for eleven days with the aqueous extract of cashew apple cakes at concentrations ranging from 150 to 300 mg.Kg-1 bw, then intoxicated with paracetamol at 2 g.Kg-1 bw, for three days. The blood of these rats was collected and submitted to biochemical analyses. Two batches of mice weighing between 20 and 30 grams, with five mice per batch, were pretreated with the same test substance at concentrations also ranging from 150 to 300 mg.Kg-1 bw, then intoxicated with paracetamol before receiving phenobarbital. Afterwards, their sleep time was evaluated. Results: In rats, paracetamol intoxication materialized by the increase in serum ALT activity ranging from 109±5.19 to 571±20.28 IU.L-1 and that of AST ranging from 144±5.77 to 428±14.19 IU.L-1. Similarly, direct bilirubin increased from 0 to 1.08± 0.58 mg.dl-1. These increases in transaminase activity and bilirubin levels were significantly decreased in rats pretreated with the aqueous extract of cashew apple cake. In mice, the phenobarbital test showed a 29.82 to 38.59% decrease in sleep time in mice pretreated with the aqueous extract of cashew apple cakes. Conclusion: The aqueous extract of cashew apple cakes influencing biochemical parameters such as ALT, AST, bilirubin and sleep time, could therefore be used in the prevention of liver diseases, in traditional medicine.

Development and validation of a method for phenobarbital in serum: anticonvulsant pharmacotherapy monitoring

The therapeutic drug monitoring (TDM) is an important strategy for the effectiveness and safety of long-term pharmacotherapy, such as the use of phenobarbital as an anticonvulsant drug in epilepsy. In this sense, HLPC has been presented as a technique for the measurement of phenobarbital in serum. However, the ideal conditions for carrying out the method must be established for each laboratory reality. An analytical method using HPLC was developed and validated in order to identify and quantify Phenobarbital in blood. The chromatographic conditions were C-18 column (Shimpack XR-ODS 50L x 3.0), acetonitrile-water mobile phase (30:70, v v-1), 0.2 mL min-1 flow and reading wavelength of 210 nm. Linearity was established in the range of 2.5 to 80 µg mL-1, the linear correlation coefficient was 0.9981. The average of the coefficient of variation of the precision was 5.30%. The relative standard error of the accuracy was -2.17% and of the recovery coefficient was 97.83%. In all eleven patients, phenobarbital concentrations were below the therapeutic range. The tested method was selective, linear, precise, accurate and showed good recovery.(AU)

Quantitative analysis of phenobarbital in biological fluids: Analyte enrichment by an electrically-assisted microextraction technique

An electrically-assisted microextraction method called electromembrane extraction, followed by a simple high performance liquid chromatography and ultraviolet detection was developed and validated for determining phenobarbital in biological samples. The major parameters influencing the electromembrane extraction procedure including solvent composition, voltage, pH of acceptor and donor solutions, salt effect, and time of extraction were evaluated and optimized. The drug was extracted from the donor aqueous sample solution (pH 9) to the acceptor aqueous solution (pH 13). The donor and acceptor phases were separated by a hollow fiber dipped in 1-octanol as a supported liquid membrane. A voltage of 40 V during 20 minutes was applied as the driving force. The enrichment factor was obtained >51 which enhanced the sensitivity of the instrument. Limit of detection and limit of quantitation were 7.5 and 25 ng/mL, respectively. The method was linear over the range of 25-1000 ng/mL for phenobarbital (R2 >0.9998) with repeatability (%RSD) between 0.4% and 6.8% (n = 3). The proposed method was successfully applied to human plasma and urine samples with relative recovery of 70-80% and %RSD < 6.8%.

Systemic and clinical treatment of gingival hyperplasia associated with use of anticonvulsant

ABSTRACT: Anticonvulsants are drugs that can modify the gingival tissues response to inflammatory processes in the presence of dental plaque, inducing gingival overgrowth. Preexisting gingival inflammation induced by dental plaque seems to be a favorable condition to the development and/or expression of gingival overgrowth. This study describes a case in which the use of phenytoin and phenobarbital anticonvulsant associated with the presence of dental plaque provided a large and severe extent of gingival alteration. We concluded that it was possible to achieve a good result in the patient with an intensive mechanical control of dental plaque, oral hygiene orientations and substitution of the drug for other alternative medication.

Effect analysis of diazepam combined with phenobarbital in the treatment of febrile convulsions in children / 中国基层医药

To investigate the clinical effect of diazepam combined with phenobarbital in the treatment of febrile convulsions in children.Methods From January 2015 to July 2017,100 children with febrile convulsions in the Women＇s and Children＇s Hospital of Ningbo were selected and divided into two groups by random number table,with 50 cases in each group.The control group was treated with diazepam ,while the observation group was treated with diazepam combined with phenobarbital.The clinical efficacy,anticonvulsive time,myocardial enzyme index,hypersensitive C-reactive protein and incidence of adverse reactions were compared between the two groups . Results (1)The total clinical effective rate of the observation group (98%) was higher than that of the control group (χ2 ＝4.891,P＜0.05),and the time of stopping convulsion [(20.92 ±4.49) min] was shorter than that of the control group(t＝5.443,P＜0.05).(2) After treatment,the creatine kinase isoenzymes [(25.93 ±12.76) U／L], phosphocreatinase [(189.47 ±7.35 ) U／L], hydroxybutyrate dehydrogenase [( 276.73 ±12.85 ) U／L ], lactate dehydrogenase[(305.94 ±13.27)U／L],hypersensitive C-reactive protein[(5.04 ±1.65)ng／L] in the observation group were lower than those in the control group (t＝4.961,5.333,5.901,6.160,5.354,all P＜0.05).(3) During the treatment period, no obvious adverse reactions occurred in both two groups.Conclusion The combination of diazepam and phenobarbital can effectively arrest febrile convulsions in children ,improve the clinical efficacy ,protect myocardial cells,it has fewer adverse reactions ,it is safe and reliable.

Effect analysis of diazepam combined with phenobarbital in the treatment of febrile convulsions in children / 中国基层医药

Objective@#To investigate the clinical effect of diazepam combined with phenobarbital in the treatment of febrile convulsions in children.@*Methods@#From January 2015 to July 2017, 100 children with febrile convulsions in the Women's and Children's Hospital of Ningbo were selected and divided into two groups by random number table, with 50 cases in each group.The control group was treated with diazepam, while the observation group was treated with diazepam combined with phenobarbital.The clinical efficacy, anticonvulsive time, myocardial enzyme index, hypersensitive C-reactive protein and incidence of adverse reactions were compared between the two groups.@*Results@#(1)The total clinical effective rate of the observation group(98%) was higher than that of the control group(χ2=4.891, P<0.05), and the time of stopping convulsion[(20.92±4.49)min] was shorter than that of the control group(t=5.443, P<0.05). (2)After treatment, the creatine kinase isoenzymes[(25.93±12.76)U/L], phosphocreatinase[(189.47±7.35)U/L], hydroxybutyrate dehydrogenase[(276.73±12.85)U/L], lactate dehydrogenase[(305.94±13.27)U/L], hypersensitive C-reactive protein[(5.04±1.65)ng/L] in the observation group were lower than those in the control group(t=4.961, 5.333, 5.901, 6.160, 5.354, all P<0.05). (3)During the treatment period, no obvious adverse reactions occurred in both two groups.@*Conclusion@#The combination of diazepam and phenobarbital can effectively arrest febrile convulsions in children, improve the clinical efficacy, protect myocardial cells, it has fewer adverse reactions, it is safe and reliable.

Comparison of sedation effect and safety between dexmedetomidine and phenobarbital sodium during perioperative period of cataract surgery / 国际眼科杂志(Guoji Yanke Zazhi)

@#AIM: To compare the clinical efficacy and safety of dexmedetomidine with phenobarbital sodium in the perioperative period of cataract surgery.<p>METHODS: A prospective study. Selected 120 cases of patients underwent cataract surgery under topical anesthesia. Before surgery, patients were administed dexmedetomidine nasal spray and phenobarbital sodium intramuscularly, respectively. Observed postoperative Visual Analogue Scale(VAS), Iowa Satisfaction with Anesthesia Scale(ISAS), perioperative vital signs and intraocular pressure, intraoperative complications and adverse drug reactions.<p>RESULTS: Compared with the phenobarbital sodium group, the dexmedetomidine group had lower VAS score and higher ISAS score, more stable intraoperative systolic blood pressure, better reduction of intraoperative intraocular pressure, lower incidence of complications and adverse drug reactions.<p>CONCLUSION: Compared with phenobarbital sodium, the administration of dexmedetomidine nasal spray in the perioperative period of cataract surgery has beneficial sedative and analgesic effection, which can improve the satisfaction of patients and increase the safety of surgery.

Tratamiento de las convulsiones neonatales / Treatment of neonatal seizures

Las convulsiones neonatales están entre las manifestaciones más dramáticas de enfermedad neurológica y deben ser consideradas una emergencia. La incidencia es 3.5 por cada 100 nacidos a término y en prematuros asciende a 58 por cada 100 nacidos vivos. Las convulsiones neonatales son una manifestación clínica de disfunción cortical no específica que puede dar lugar a daño permanente del cerebro. La etiología es multifactorial y requiere una evaluación cuidadosa de cada escenario clínico. El diagnóstico es más complejo por el hecho de que la mayoría de convulsiones son sub-clínicas o sutiles y a veces no tienen correlación con el electroencefalograma. Aunque la identificación temprana y el tratamiento son críticos, el diagnóstico se complica por algunos factores como la variedad de presentaciones clínicas, diferentes etiologías y varias alternativas de tratamiento. De todas maneras, los estudios de investigación y la evidencia clínica disponible han demostrado que el tratamiento precoz con fármacos anticonvulsivantes puede mejorar el pronóstico.

Neonatal seizures are among the most dramatic manifestations of acute central nervous system dysfunction. The incidence is much higher in very low weight neonates than in full term infants (~58 and 3.5 per 100 live births, respectively). Neonatal seizures represent the clinical manifestation of a non-specific cortical cerebral dysfunction which can lead to permanent brain injury. The etiology is multifactorial and requires a judicious assessment for each clinical scenario. The diagnosis is further complicated by the fact that most neonatal seizures are subclinical, that is, may display very subtle or no clinical changes and the diagnosis may just be based on EEG findings. The treatment depends on the etiology, but an early and opportune intervention prevents further brain damage, thus improving prognosis. Although early identification and treatment are critical, the diagnosis of neonatal seizures is complicated by several factors such as different clinical presentations, possible etiologies and several treatment options. Nevertheless, research studies and clinical evidence have shown that early treatment with anti-seizure medications can change the outcome.

The effectiveness of continuous venovenous hemodiafiltration in phenobarbital intoxication

Phenobarbital continues to be widely used in childhood epilepsy. Incorrect drug prescription can sometimes lead to intoxication, particularly in young children. A 40-month-old female infant presented to our emergency department due to failure to awaken. The patient was assessed in terms of etiology of coma, and her history revealed that she had been given a 100 mg phenobarbital pill instead of 15 mg. Her blood phenobarbital level was high (>80 mg/dl). At physical examination, her Glasgow coma score was 6, the pupils were isochoric, pupillary light reflex was bilateral positive, deep tendon reflexes were absent, respiration was superficial, and pulmonary bilateral diffuse secretory rales were present, and the patient was intubated. Continuous venovenous hemodiafiltration (CVVHDF) was performed due to prolonged coma, intubation, and potentially fatal phenobarbital level. Blood phenobarbital levels at 4 and 12 h improved to >80 and 33.4 mg/dl, and the patient was extubated at 14 h. CVVHDF was effective in intoxication despite long-acting barbiturate phenobarbital not binding to protein. We think that this is a useful method capable of use in phenobarbital intoxications.

Design and practice of phenobarbital comprehensive experiment / 中华医学教育探索杂志

A set of comprehensive chemical experiments was designed for the second-year undergraduate majoring in pharmacy which contained synthesis,refinement,structural identification and appraisal analysis and assaying in phenobarbital.The purpose of the experiment was to improve the comprehensive strength,the ability of investigation and operation.The paper mainly discusses the design and application of the comprehensive experiment in the phenobarbital for pharmacy and Chinese medicine majors from the following aspects including design idea,teaching plan,effectiveness and popularization.

Síndrome de abstinencia neonatal debido a exposición prenatal al citalopram: a propósito de un caso / Neonatal abstinence syndrome due to prenatally citalopram exposure: A case report

El síndrome de abstinencia neonatal (SAN) debido a la exposición prenatal al citalopram se desarrolla durante los primeros días de vida, incluso con una exposición al fármaco en dosis bajas. El tratamiento de apoyo es la primera opción, aunque puede usarse el fenobarbital en el tratamiento de este síndrome. No debe interrumpirse la lactancia. Debe hacerse un seguimiento de estos recién nacidos para establecer el desenlace del SAN y las consecuencias en el desarrollo neurológico. En este artículo presentamos el caso de un recién nacido con SAN debido a exposición al citalopram en una dosis más baja que lo informado previamente en la bibliografía durante los últimos seis meses del embarazo. Se utilizó el fenobarbital debido al fracaso del tratamiento no farmacológico.

Neonatal abstinence syndrome (NAS) due to prenatally exposure to citalopram can develop during the first days of life even with low dose of drug exposure. Supportive management is the first choice but phenobarbital can be used in treatment of this syndrome. Breastfeeding should not be interrupted. These neonates should be followed both for NAS and neurodevelopmental outcome. In this article, we reported a newborn with NAS due to citalopram exposure with a lower dose than previously reported in the literature, during the last six months of pregnancy. Phenobarbital was used because of non-pharmacological treatment failure.

Intravenous levetiracetam versus phenobarbital in children with status epilepticus or acute repetitive seizures / 소아과

PURPOSE: This study compared the efficacy and tolerability of intravenous (i.v.) phenobarbital (PHB) and i.v. levetiracetam (LEV) in children with status epilepticus (SE) or acute repetitive seizure (ARS). METHODS: The medical records of children (age range, 1 month to 15 years) treated with i.v. PHB or LEV for SE or ARS at our single tertiary center were retrospectively reviewed. Seizure termination was defined as seizure cessation within 30 minutes of infusion completion and no recurrence within 24 hours. Information on the demographic variables, electroencephalography and magnetic resonance imaging findings, previous antiepileptic medications, and adverse events after drug infusion was obtained. RESULTS: The records of 88 patients with SE or ARS (median age, 18 months; 50 treated with PHB and 38 with LEV) were reviewed. The median initial dose of i.v. PHB was 20 mg/kg (range, 10-20 mg/kg) and that of i.v. LEV was 30 mg/kg (range, 20-30 mg/kg). Seizure termination occurred in 57.9% of patients treated with i.v. LEV (22 of 38) and 74.0% treated with i.v. PHB (37 of 50) (P=0.111). The factor associated with seizure termination was the type of event (SE vs. ARS) in each group. Adverse effects were reported in 13.2% of patients treated with i.v. LEV (5 of 38; n=4, aggressive behavior and n=1, vomiting), and 28.0% of patients treated with i.v. PHB (14 of 50). CONCLUSION: Intravenous LEV was efficacious and safe in children with ARS or SE. Further evaluation is needed to determine the most effective and best-tolerated loading dose of i.v. LEV.

Simultaneous Determination of Phenobarbital,Ibuprofen and Nikethamide in the Biomaterial with GC-MS / 昆明医科大学学报

Objective The study aimed to establish a kind of simple,rapid,accurate and reliable method in order to simultaneous determine the phenobarbital,ibuprofen and nikethamide in the biomaterial. Methods The biomaterial were pre-treated with ethanol(v/v 95%)at pH 3~4 and then was extracted with ethyl acetate at pH 3~4 and 10~11,respectively. Finally,phenobarbital,ibuprofen and nikethamide in the biomaterial were simultaneous detected by GC-MS. The retention times and relevant characteristic fragment ions of the three substances in the total ion current(TIC)and the mass spectrogram could be used as the basis of qualitative analysis. Results The method was simple and easy operation. It has the characteristics of low background interference,good separation effect and fast analytical speed. The retention times of phenobarbital,ibuprofen and nikethamide were 8.472 min,7.087 min and 6.655 min,respectively. The characteristic fragment ions of phenobarbital were 204 and 232(m/z),of ibuprofen were 161 and 206(m/z),and of nikethamide were 106 and 177(m/z). Conclusion The method showed a satisfactory result that it could be applied to simultaneous determine phenobarbital,ibuprofen and nikethamide of the biomaterial for forensic toxicological analysis.

Exploration and efficacy assessment of the model for epilepsy management in rural China / 中华神经科杂志

Objective To evaluate the applicability and effectiveness of the model for managing patients with convulsive epilepsy in rural China.Methods The model is under leadership of the government departments and medical institutions at all levels organized primary physicians for treatment and management.People with convulsive epilepsy in 24 rural areas were screened by local physicians and confirmed by neurologists.Patients diagnosed with convulsive epilepsy and agreed with managing were recruited into study.They were managed at primary care level and provided with phenobarbital monotherapy.Efficacy was assessed from the changes in seizure frequencies from baseline.Results There were 408 town hospitals and 979 trained primary care physicians participating in our study.Five thousand and thirty-eight patients were enrolled in 2 years,and 90％ patients with good compliance.Among the people who were treated with phenobarbital monotherapy,3 170 were managed for 12 months,and 2 005 (63.3％) of whom had a 50％ or greater reduction in seizure frequency and 1 246 (39.3％)patients remained seizure free;651 patients were managed for 24 months,and 491 (75.4％) of whom had a 50％ or greater reduction in seizure frequency and 202(31.0％)patients remained seizure free.Three hundred and forty-three (6.8％) patients withdrew from the study,and only 35 (0.7％) patients discontinued treatment because of side effects.Sixty-nine (1.4％) patients were dead and 8 (11.6％) of them were caused by status epilepticus.Conclusion This study confirms that this model is beneficial to patients with epilepsy and is suitable to the rural areas of China.

The random and comparative study on therapeutic effect and safety between Levetiracetam and Phenobarbitaladministration for neonatal seizures / 中华实用儿科临床杂志

Objective To randomly compare the therapeutic effect and safety between Levetiracetam (LEV) and Phenobarbital (PB) in the treatment of neonatal seizures.Methods A total of 61 infants with acute convulsion were randomly divided into 2 groups:LEV group (n =30) and PB group (n =31) during January 2013 to December 2014 in Urumqi Children's Hospital.All neonates received routine management including etiology treatment and adverse drug reaction monitoring.In the LEV group,subjects received oral formulation of LEV with initial loading dose 30 mg/kg,followed by 15 mg/kg twice a day.If the seizures were not controlled completely,PB treatment was added until seizures were completed controlled.If seizures were controlled quickly,the dose of PB was gradually reduced and LEV was used as monotherapy.The subjects in PB group received intramuscular or intravenous injection of PB with 10 mg/kg as the first dose,then 5 mg/(kg · d) oral PB was administered,if seizures were not controlled,LEV treatment was added,then dose of PB was gradually reduced until seizures were controlled completely,and then patients were switched to LEV monotherapy gradually.The drug adverse reactions were observed.Results (1) After LEV or PB monotherapy,66.7％ (20/30 cases) and 54.8％ (17/31 cases) of the subjects obtained sustainable seizure free respectively.Although,there was a higher control ratio in LEV group,but no significant difference was observed between the 2 groups (P ＞0.05).(2) LEV group (16/30 cases,53.33％) had higher rapid seizure control ratio with seizure controlled within 24 h after first dosage administration than that of PB group (8/31 cases,25.80％),and there was significant difference (x2 =4.841,P =0.028).Further more,if adding the cases who had to change to use another comparative one (LEV or PB) due to their seizures failure control with the first one treated,LEV group (21/44 cases,47.72％) still had higher rapid seizure control ratio in total patients than that of PB group(10/41 cases,24.39％),and there was significant difference (x2 =4.988,P =0.026).(3) Eight cases who changed to LEV after PB as the first treatment drug failed obtained sustainable seizure free.(4) One case in PB group with transient urinary retention was observed but the symptom disappeared 36 h after PB withdrawal,and no significant drug adverse reaction was observed in LEV group.Conclusion LEV is more rapid and safe for seizure control of neonates than PB.

Efficacy and its related factors of phenobarbital treatment for epilepsy management in rural China / 中华全科医师杂志

Objective To analyze efficacy and its influencing factors of phenobarbital treatment for epilepsy management in rural China.Methods Total 3 315 patients with convulsive epilepsy from rural areas of 24 counties were enrolled in this joint epilepsy management program.All patients received phenobarbital monotherapy for 1 year during November 2011 to November 2013.The efficacy and potential influencing factors including sex,age,duration of epilepsy,number of seizures in the 12 months before management(≥2),previous treatment,daily dose of phenobarbital,taking other antiepileptic drugs and compliance of patients were studied with multivariate analysis.Results Among 3 315 patients,38.9％ were seizure-free during the entire management period.The rates of seizure-free in 15 to 39 y age group (35.2％,495/1 405)and in patients receiving irregular treatment previously (34.6％,625/1 808)were lower.The rates of seizure-free were higher in patients taking phenobarbital 60-90 mg everyday (49.4％,988/2 000) and those with good compliance(42.3％,1 160/2 744).Patients taking other antiepileptic drugs in 12 months had lower seizure-free rate (31.0％,45/145).Univariate analysis showed that gender of patients was not related to seizure-free rate (P ＞ 0.1).Multivariate analysis showed that the longer duration of epilepsy(OR =0.015,95％ CI:1.008-1.021,P ＜ 0.001),more seizures in the 12 months (OR =0.005,95％ CI:1.002-1.007,P =0.002) and the irregular treatment before management were the risk factors for low seizure-free rate (P ＜ 0.05).Patients received formal treatment or untreated had a lower risk of seizure compare with the irregular treatment (OR =0.737,95％ CI:0.611-0.889,P =0.001;OR =0.566,95％ CI:0.469-0.683,P ＜0.001).Patients with good compliance and with a daily dose of 60-89 mg phenobarbital(OR =0.107,95％ CI:0.013-0.905,P =0.040) were associated with high seizurefree rate;in contrast the poor compliance was a risk factor for not being seizure-free(OR =2.038,95％ CI:1.634-2.541,P ＜ 0.001).Conclusion Regular medication of phenobarbital with good compliance is effective for convulsive epilepsy management in rural China.

Simultaneous Determination of Carbamazepine and Phenobarbital in Human Plasma by UPLC-MS/MS / 中国药师

Objective: To establish an ultra performance liquid chromatography-tandem quadrupole mass spectrometry ( UPLC-MS/MS) method to determine the concentration of carbamazepine and phenobarbital in human plasma, and apply in the clinical moni-toring. Methods:Diazepam was used as the internal standard, and the samples were precipitated by acetonitrile. An ACQUITY UPL-C? BEH C18 (50 mm × 2. 1 mm, 1. 7 μm) column was used as the stationary phase at 40℃ with a Waters XEVO TQD. The mobile phase consisted of acetonitrile (containing 10 mmol·L-1 ammonium formate) and water (containing 10 mmol·L-1 ammonium for-mate and 0. 1% formic acid) with gradient elution pumped at a flow rate of 0. 4 ml·min-1 . ESI was applied and the samples were scanning analyzed by positive ion multi-reaction monitoring mode. The plasma was precipitated by 200 μl acetonitrile and centrifugated at 12 000 × g for 10 min and tranfer it into an Ep tube. The sample size was 20 μl. Results:The retention time of carbamazepine was 1. 23 min. Excellent linear calibration curves of carbamazepine were obtained within the concentration range of 0. 25-25μg·ml-1(r=0. 999 7). The lower limit of quantification of carbamazepine was 0. 01 μg·ml-1. The retention time of phenobarbital was 1. 11 min. Excellent linear calibration curves of carbamazepine were obtained within the concentration range of 0. 5-50 μg·ml-1(r=0. 999 6). The lower limit of quantification of carbamazepine was 0. 05 μg·ml-1. The recovery of three concentrations of carbamazepine was (82. 1 ± 6. 83)%, (82. 91 ± 4. 3)% and (84. 35 ± 3. 09)%, and the recovery of three concentrations of phenobarbital was (84. 27 ± 6. 91)%, (84. 32 ± 7. 74)% and (89. 07 ± 6. 24)%, respectively. The intra- and inter-day RSDs were all less than 10%. There were no endogenous substances existing in the incubation system, therefore, there was no interference with the determination. Conclu-sion:The simple, accurate and rapid method is suitable for the determination of carbamazepine and phenobarbital in human plasma, which can contribute greatly to the therapeutic drug monitoring service for patients.

Determination of phenobarbital in biomaterial / 国际检验医学杂志

Objective To establish a kind of simple ,rapid ,accurate and reliable method to determine the phenobarbital in the biomaterial .Methods We pre‐treated biomaterial by the method that the reagent of acetone∶water (v/v 8∶2) was firstly used to soak the biomaterial ,and then we took use of ethyl acetate as reagent to extract the phenobarbital of the biomaterial in the present of pH=3-4 .We finally employed GC‐MS to determine these samples .On the one hand ,we not only took advantage of the reten‐tion time of the phenobarbital in total ion current (TIC) but also took advantage of the characteristic fragment ions of phenobarbital in mass spectrogram as qualitative basis .On the other hand ,we took advantage of the external standard method as quantitative ba‐sis .Results The method had the characteristics of the simple and easy operation .There was hardly background interference and there was good separation effect in the method .The method also had the characteristics of fast analytical speed such as the retention time of the phenobarbital was 8 .385 min .The characteristic fragment ions of phenobarbital was m/z 204 and m/z 232 .The charac‐teristic fragment ions of m/z 204 was served as quantitative ion fragments and we employed the external standard method to quanti‐fy in the method .In short ,the average recovery rate of the method was 87 .35% .Relative standard deviation (RSD) was 5 .43% in the method .The lowest limit of detection (LLOD) was 0 .005 mg/mL .Conclusion The method showes satisfactory result that it could be applied to determine the phenobarbital of the biomaterial of forensic toxicological analysis .

Phenobarbital loaded microemulsion: development, kinetic release and quality control

ABSTRACT This study aimed to obtain and characterize a microemulsion (ME) containing phenobarbital (PB). The PB was incorporated in the proportion of 5% and 10% in a microemulsion system containing Labrasol(r), ethanol, isopropyl myristate and purified water. The physicochemical characterization was performed and the primary stability of the ME was evaluated. An analytical method was developed using spectrophotometry in UV  = 242 nm. The kinetics of the in vitro release (Franz model) of the ME and the emulsion (EM) containing PB was evaluated. The incorporation of PB into ME at concentrations of 5 and 10% did not change pH and resistance to centrifugation. There was an increase in particle size, a decrease of conductivity and a change in the refractive index in relation to placebo ME. The ME remained stable in preliminary stability tests. The analytical method proved to be specific, linear, precise, accurate and robust. Regarding the kinetics of the in vitro release, ME obtained an in vitro release profile greater than the EM containing PB. Thus, the obtained ME has a potential for future transdermal application, being able to compose a drug delivery system for the treatment of epilepsy.

RESUMO O objetivo deste trabalho foi obter e caracterizar uma microemulsão (ME) contendo fenobarbital (FEN). O FEN foi incorporado na proporção de 5% e 10% em um sistema microemulsionado composto por labrasol(r), etanol, miristato de isopropila e água purificada. Foi realizada a caracterização físico-química e avaliada a estabilidade preliminar da ME. Desenvolveu-se um método analítico por espectrofotometria em UV  = 242 nm. Foi avaliada a cinética de liberação in vitro (em modelo de Franz) da ME e da emulsão (EM) contendo FEN. A incorporação do FEN em ME nas concentrações de 5 e 10% não alterou o pH e a resistência à centrifugação. Houve aumento do tamanho da partícula, redução da condutividade e alteração do índice de refração em relação à ME placebo. A ME manteve-se estável nos ensaios de estabilidade preliminar. O método analítico demonstrou ser específico, linear, preciso, exato e robusto. Na cinética de liberação in vitro, a ME obteve um perfil de liberação in vitro superior a EM contendo FEN. Desta forma, a ME obtida tem potencial para uma futura aplicação transdérmica, podendo compor um sistema de liberação de fármacos para tratamento da epilepsia.