Effects of Anesthetic Administration on Rat Hypothalamus and Cerebral Cortex Peptidome.

Prohormone-derived neuropeptides act as cell-cell signaling molecules to mediate a wide variety of biological processes in the animal brain. Mass spectrometry-based peptidomic experiments are valuable approaches to gain insight into the dynamics of individual peptides under different physiological conditions or experimental treatments. However, the use of anesthetics during animal procedures may confound experimental peptide measurements, especially in the brain, where anesthetics act. Here, we investigated the effects of the commonly used anesthetics isoflurane and sodium pentobarbital on the peptide profile in the rodent hypothalamus and cerebral cortex, as assessed by label-free quantitative peptidomics. Our results showed that neither anesthetic dramatically alters peptide levels, although extended isoflurane exposure did cause changes in a small number of prohormone-derived peptides in the cerebral cortex. Overall, our results demonstrate that acute anesthetic administration can be utilized in peptidomic experiments of the hypothalamus and cerebral cortex without greatly affecting the measured peptide profiles.

Development of an Analytical Method for Detection of Anesthetics and Sedatives in Fish.

BACKGROUND: Anesthetics and sedatives are frequently used to prevent abrasions caused by stress and to facilitate fish management. However, drug residues may persist and cause changes in fish conditions and induce side effects. In addition, drugs that are not permitted for use in edible fish are sometimes potentially used in fish. The drugs can also be found in wastewater and are likely to be detected in fish. OBJECTIVE: The purpose of this study was to establish a quantitative analytical method for 10 anesthetic and sedative (azaperone, chlorpromazine, diazepam, estazolam, haloperidol, nitrazepam, nordiazepam, oxazepam, perphenazine, and temazepam) residues in fish sold in Korean markets. METHOD: Shrimp, flounder, and eel samples were selected as matrices. Acetonitrile (ACN) containing 0.1% formic acid was selected as an extraction solvent for shrimp and 100% ACN for flounder and eel. The QuEChERS method with C18 and primary secondary amine (PSA) was used as the extraction procedure, and the analysis was performed by liquid chromatography-tandem mass spectrometry (LC-MS/MS). RESULTS: Limit of quantitation, recovery, accuracy, and precision were validated, and satisfactory results were obtained for the drugs. All results applied to the real samples were negative. CONCLUSIONS: An optimal validation method was studied. Since the results for all samples were negative, it is considered that additional studies are needed by increasing the number of drugs. HIGHLIGHTS: The most effective QuEChERS pretreatment method and conditions of LC-MS/MS for the analysis of anesthetics and sedatives in fish were established.

Effects of Occupational Exposure to Waste Anesthetic Gas on Oxidative Stress and DNA Damage.

OBJECTIVE: The aim of the study was to investigate the potential effects of waste anesthetic gas (WAG) on oxidative stress, DNA damage, and vital organs. METHODS: A total of 150 members of the staff at a hospital were assigned to an exposure group or control group. The 68 operating room (OR) staff in the exposure group were exposed to WAG, and the 82 non-OR staff in the control group were not exposed to WAG. Air samples were collected in the OR, and the sevoflurane concentrations in the samples were determined. Superoxide dismutase (SOD), glutathione peroxidase (GSH-px), and malondialdehyde (MDA) in plasma from the participants were determined to assess oxidative stress. Western blot analysis was used to detect γH2AX in peripheral blood to assess DNA damage. Hematopoietic parameters, liver function, kidney function, and changes in electrophysiology were assessed to identify the effects on the vital organs. RESULTS: The mean (±standard deviation) sevoflurane concentration in 172 air samples from 22 operating rooms was 1.11 ± 0.65 ppm. The superoxide dismutase activity and vital organ parameters (lymphocyte, hemoglobin, and total protein concentrations and heart rate) were significantly lower (P < 0.05) in the exposed group than the control group. The malondialdehyde, total bilirubin, and creatinine concentrations and QT and QTc intervals were significantly higher (P < 0.05) in the exposed group than the control group. There were no significant differences between the glutathione peroxidase activities and γH2AX concentrations for the exposed and control groups. CONCLUSIONS: Long-term occupational exposure to waste anesthetic gas may affect the antioxidant defense system and probably affects vital organ functions to some extent. No correlation between DNA damage and chronic exposure to WAG was observed.

Evaluation of benzocaine-based anesthetic gel in anuran skins extracts: A case study using the frog Lithodytes lineatus (Anura: Leptodactylidae).

Extracts made from the skin of dead Lithodytes lineatus frog individuals with the application of the benzocaine-based anesthetic gel, introduced into the oral cavity, were analyzed by 1H Nuclear Magnetic Resonance to investigate whether the application of this product (oral) can make studies that use extracts from the skins of these animals unfeasible. For comparison, we used skins of another species of anuran following the same death protocol. No trace of the benzocaine substance was found in the 1H-NMR spectra of the skin extracts from any of the tested anuran species. Still, using the hierarchical clustering model, it was possible to observe the formation of well-defined groups between the skin extracts of anurans and the anesthetic used to kill these animals. Our results suggest that the lethal dose of benzocaine in gel used inside the mouth of frogs may have no influence on potential results regarding the chemical composition or even bioassays using extracts made from the skin of these animals killed under this protocol since there was no detection of this substance for the analyzed samples.

Forced degradation studies of norepinephrine and epinephrine from dental anesthetics: Development of stability-indicating HPLC method and in silico toxicity evaluation.

Injectable solutions containing epinephrine (EPI) and norepinephrine (NE) are not stable, and their degradation is favored mainly by the oxidation of catechol moiety. As studies of these drugs under forced degradation conditions are scarce, herein, we report the identification of their degradation products (DP) in anesthetic formulations by the development of stability-indicating HPLC method. Finally, the risk assessment of the major degradation products was evaluated using in silico toxicity approach. HPLC method was developed to obtain a higher selectivity allowing adequate elution for both drugs and their DPs. The optimized conditions were developed using a C18 HPLC column, sodium 1-octanesulfonate, and methanol (80:20, v/v) as mobile phase, with a flow rate of 1.5 mL/min, UV detection at 199 nm. The analysis of standard solutions with these modifications resulted in greater retention time for EPI and NE, which allow the separation of these drugs from their respective DPs. Then, five DPs were identified and analyzed by in silico studies. Most of the DPs showed important alerts as hepatotoxicity and mutagenicity. To the best of our acknowledgment, this is the first report of a stability-indicating HPLC method that can be used with formulations containing catecholamines.

A special case of medicine in disguise: Tattoo inks containing anaesthetics.

This paper describes a case of medicine in disguise: seized tattoo inks containing lidocaine and tetracaine at high concentration. Identification of anaesthetics was performed by LC MS Q-TOF with ESI+ source, by accurate mass measurement and by comparing the fragmentation patterns of molecular ions, at 30 V and 10 V of collision-offset voltage, with reference standards. Quantification was also performed by LC MS Q-TOF on the chromatographic peaks in the extracted ion chromatograms, by calibration curves obtained at different standard concentrations and by standard additions approach. The measurement uncertainty was estimated from validation data. The paper gives also chromatographic parameters, MS and MS/MS data and a quantitation method, with a full validation, of other six "caines". Thus the paper intends to provide a tool for identification and quantitation of the most common local anaesthetics that could be fraudulently added to tattoo inks. The results here reported show that the seized samples of inks represent a serious health risk owing to the high anaesthetic content - therapeutic-like dosage - found.

Stress-reducing and anesthetic effects of the essential oils of Aloysia triphylla and Lippia alba on Serrasalmus eigenmanni (Characiformes: Serrasalmidae)

Anesthetic effect of Aloysia triphylla and Lippia alba essential oils (EOs) in the Amazonian fish Serrasalmus eigenmanni was evaluated. The fish were placed in aquaria containing A. triphylla or L. alba EOs (25 to 200 µL L-1). Then, fish were transferred to aquaria containing EO-free water to evaluate their recovery time. In another experiment, fish were transferred to aquaria containing A. triphylla or L. alba EOs (3 to 10 µL L-1) and swimming behavior was analyzed for up to 240 min of exposure. Water samples were collected at 0 and 240 min and blood samples were collected at 240 min. Tested concentrations induced all stages of anesthesia, except 25 µL L-1 A. triphylla EO and 50 µL L-1 L. alba EO, which only induced sedation. Prolonged exposure to both EOs reduced swimming time compared to the control at all evaluated times. The fish exposed to 3 µL L-1 A. triphylla EO showed a lower net K+ efflux compared to ethanol-exposed fish; in those exposed to 5 µL L-1, ammonia excretion was reduced. The blood parameters did not show significant differences between treatments. In conclusion, both EOs can be used as anesthetics and sedatives for transport of S. eigenmanni.(AU)

Avaliou-se o efeito anestésico dos óleos essenciais de Aloysia triphylla e de Lippia alba no peixe amazônico Serrasalmus eigenmanni. Os peixes foram colocados em aquários contendo OEs de A. triphylla ou L. alba (25 a 200 µL L-1). Após, foram transferidos para aquários com água sem anestésicos para avaliar o tempo de recuperação. Em outro experimento, peixes foram transferidos para aquários contendo OEs de A. triphylla ou L. alba (3 a 10 µL L-1) e o comportamento natatório foi analisado até 240 min de exposição. Foram coletadas amostras de água em 0 e 240 min e de sangue em 240 min. As concentrações testadas induziram todos estágios de anestesia, exceto 25 µL L-1 OE de A. triphylla e 50 µL L-1 OE de L. alba, que causaram somente sedação. Exposição prolongada a ambos OEs reduziu o tempo de natação comparado ao controle. Peixes expostos a 3 µL L-1 OE de A. triphylla apresentaram menor efluxo de K+ comparado aos expostos ao etanol e nos expostos a 5 µL L-1 a excreção de amônia reduziu. Parâmetros sanguíneos não diferiram entre tratamentos. Conclui-se que ambos OEs podem ser utilizados como anestésicos e no transporte de S. eigenmanni.(AU)

Was Mafeisan an Anesthetic in Ancient China?

According to the Chinese historical books, Records of the Three Kingdoms () and Book of the Later Han (), Hua Tuo (, 140 - 208), a Traditional Chinese medicine (TCM) physician invented Mafeisan, an oral herbal general anesthetic, more than 1800 years ago during Eastern Han Dynasty. However, no written record of ingredients of the original Mafeisan has been found anywhere so far although there have been several similar anesthetic prescriptions published in TCM books later. There has been controversy over the existence of Mafeisan and even Hua Tuo in Chinese literature. We did extensive literature search and analysis, and believe that there indeed was Mafeisan in Hua Tuo's time.

Validated chromatographic method for the simultaneous determination of eight drugs (morphine, ropivacaine, bupivacaine, baclofen, clonidine, sufentanil, fentanyl and ziconotide) for intrathecal analgesia.

Intrathecal analgesia has increased over the past two decades in various indications: chronic refractory pain from cancerous or non-cancerous origins, spasticity. These different indications involve the use of different molecules alone or in combination such as morphine, ropivacaine, bupivacaine, fentanyl, sufentanil, clonidine, baclofen and ziconotide. Pump refills are prepared at the pharmacy under a laminar flow hood. An analytical control should be carried out before release of the preparation. A new method of analytical control by chromatography has been developed and validated according to the International Conference on Harmonization guideline in order to secure the production process.

Pharmacokinetic of florfenicol in pulmonary epithelial lining fluid of swine and effects of anesthetic agent on drug plasma disposition kinetics / Farmacoqu'imica de florfenicol em fluido de epitélio pulmonar de suínos e efeitos de agente anestésico em cinética de droga em plasma

The primary objective of the current study was to compare the pharmacokinetic (PK) of florfenicol (FFL) in pulmonary epithelial lining fluid and the plasma in swine. The second objectives were to evaluate the effect of anesthesia with ketamine and propofol on the PK of FFL in plasma. Bronchoaveolar lavage was utilized for quantification of PELF volume and the urea dilution method was used to determine the concentration of FFL in PELF. FFL was administered intramuscularly (IM) to swine in a single dose of 20mg/kg body weight. The main PK parameters of FFL in plasma and PELF were as follows: the area under the concentration-time curve, maximal drug concentration, elimination half-life and mean residence time were 69.45±4.36 vs 85.03±9.26µg·hr/ml, 4.65±0.34 vs 5.94±0.86µg/ml, 9.87±1.70 vs 10.69±1.60hr and 12.75±0.35 vs 14.46±1.26hr, respectively. There was no statistically significant difference between the PK profiles of FFL for the anesthetized and unanesthetized pigs. This study suggest that (i) FFL penetrated rapidly into the pulmonary and the drug concentration decay faster in plasma than in the pulmonary, (ii) the PK profile of FFL in swine was not interfered after administration of anesthetic agent.(AU)

O objetivo primário desse estudo foi comparar a farmacocinética de florfenicol (FFL) em fluido epitelial pulmonar à farmacocinética (PK) de FFL em plasma suíno. O segundo objetivo foi avaliar o efeito de anestesia com ketamina e propofol no PK de FFL em plasma. Lavagem broncoalveolar foi utilizada para quantificar volume de fluido epitelial pulmonar (PELF) e método de diluição de uréia para determinar FFL em PELF. Injeção de FFL foi administrada intramuscular a suínos em dose única de 20mg/kg de peso corporal. Os principais parâmetros de PK em FFL em plasma e PELF foram os seguintes: a área sob a curva de concentração-tempo, concentração máxima da droga, eliminação de meia-vida e média de tempo de permanência foram 69,45±4,36 vs 85,03±9,26µg·hr/ml, 4,65±0,34 vs 5,94±0,86µg/ml, 9,87±1,70 vs 10,69±1,60hr e 12,75±0,35 vs 14,46±1,26hr, respectivamente. Não houve diferença estatisticamente significante entre os perfis de PK de FFL para os porcos anestesiados e não anestesiados. Esse estudo sugere que (i) FFL penetrou rapidamente no pulmão e concentração da droga sofre queda mais veloz em plasma que líquido pulmonar, (ii) o perfil de PK de FFL em suínos não modificou após administração de agente anestésico.(AU)

Anesthetic synergy between two n-alkanes.

OBJECTIVE: N-butane and n-pentane can both produce general anesthesia. Both compounds potentiate γ-aminobutyric acid type A (GABAA) receptor function, but only butane inhibits N-methyl-d-aspartate (NMDA) receptors. It was hypothesized that butane and pentane would exhibit anesthetic synergy due to their different actions on ligand-gated ion channels. STUDY DESIGN: Prospective experimental study. ANIMALS: A total of four Xenopus laevis frogs and 43 Sprague-Dawley rats. METHODS: Alkane concentrations for all studies were determined via gas chromatography. Using a Xenopus oocyte expression model, standard two-electrode voltage clamp techniques were used to measure NMDA and GABAA receptor responses in vitro as a function of butane and pentane concentrations relevant to anesthesia. The minimum alveolar concentrations (MAC) of butane and pentane were measured separately in rats, and then pentane MAC was measured during coadministration of 0.25, 0.50 or 0.75 times MAC of butane. An isobole with 95% confidence intervals was constructed using regression analysis. A sum of butane and pentane that was statistically less than the lower-end confidence bound isobole indicated a synergistic interaction. RESULTS: Both butane and pentane dose-dependently potentiated GABAA receptor currents over the study concentration range. Butane dose-dependently inhibited NMDA receptor currents, but pentane did not modulate NMDA receptors. Butane and pentane MAC in rats was 39.4±0.7 and 13.7±0.4 %, respectively. A small but significant (p<0.03) synergistic anesthetic effect with pentane was observed during administration of either 0.50 or 0.75×MAC butane. CONCLUSIONS: Butane and pentane show synergistic anesthetic effects in vivo consistent with their different in vitro receptor effects. CLINICAL RELEVANCE: Findings support the relevance of NMDA receptors in mediating anesthetic actions for some, but not all, inhaled agents.

Rapid detection of five anesthetics in tilapias by in vivo solid phase microextraction coupling with gas chromatography-mass spectrometry.

The concentration of five rapidly metabolized anesthetics in living tilapias was determined in this study, by the presented method coupling in vivo solid phase microextraction (SPME) to gas chromatography-mass spectrometry (GC-MS), which was the first time that in vivo sampling method was adapted in detecting the anesthetic residue in the living aquatic product. The analytical performance of the developed method was evaluated in homogenized tilapia dorsal muscle, and the results demonstrated that the present method possessed low detection limits 1.7-9.4ngg-1), wide linear ranges (10 or 30-5000ngg-1), and satisfactory reproducibility (relative standard deviations no more than 8.1% and 10.8% for inter-fiber and intra-fiber assays, respectively). Standard curves were established in homogenized tilapia dorsal muscle for calibrating in vivo SPME in living tilapias. And the concentrations determined by in vivo SPME were close to those determined by the liquid extraction. By using the present method, one anesthetic residue was detected above the detection limit in tilapias from the local markets. Comparing to traditional methods, the present one exhibited superior time-efficiency and cost performance, as the extraction time was only ten minutes, which was short to successfully avoid the possible loss of analytes caused by elimination and sample storage. In addition, owing to the time-efficiency of the present method, the elimination of the anesthetics in tilapias was traced successfully in the laboratory.

Computerized electrocardiogram in agoutis (Dasyprocta prymnolopha Wagler, 1831) anesthetized with ketamine and midazolam / Eletrocardiografia computadorizada em cutias (Dasyprocta prymnolopha Wagler, 1831) anestesiadas com cetamina e midazolam

An electrocardiogram is a test that assesses heart electrical activity and is applied more frequently in the veterinary care of wild animals. The present study aimed to define the electrocardiogram pattern of agoutis (Dasyprocta prymnolopha Wagler, 1831) anesthetized with ketamine and midazolam. Eighteen clinically healthy agoutis (D. prymnolopha) were used from the Nucleus for Wild Animal Studies and Conservation (NEPAS) of the Federal University of Piauí, Brazil. The animals were chemically restrained with 5% ketamine hydrochloride at a dose of 15mg/kg and midazolam at a dose of 1mg/kg by intramuscular injection. Electrocardiogram tests were carried out by a computerized method with the veterinary electrocardiogram [Acquisition Model for Computer (ECG - PC version Windows 95) Brazilian Electronic Technology (TEB) consisting of an electronic circuit externally connected to a notebook computer with ECGPC-VET (TEB) software installed on the hard disc. In analysing the EKG results, significant differences were observed for QRS complex duration, PR and QT intervals and for R wave millivoltage between the genders; but we observed a significant influence of weight despite the gender. In the present experiment, the anaesthetic protocol was shown to be well tolerated by the agoutis, and no arrhythmias occurred during the time the animals were monitored. The reference values obtained should be used to better understand the cardiac electrophysiology of the species and for its clinical and surgical management.(AU)

O eletrocardiograma computadorizado é um dos meios de diagnóstico utilizado para avaliação do coração e vem sendo cada vez mais presente na rotina veterinária. Este trabalho teve por objetivo definir o padrão eletrocardiográfico de cutias (D. prymnolopha) anestesiadas com cetamina e midazolam. Foram utilizadas 18 cutias clinicamente saudáveis, provenientes do Núcleo de Estudos e Preservação de Animais Silvestres (NEPAS) da Universidade Federal do Piauí. Os animais foram submetidos à contenção química com cloridrato de cetamina a 5% na dosagem de 15mg/kg associado ao midazolam, na dosagem de 1mg/kg, por via intramuscular. Os exames eletrocardiográficos foram realizados pelo método computadorizado, com o eletrocardiógrafo veterinário (Módulo de Aquisição de ECG Para Computador (ECG - PC versão Windows 95) Tecnologia Eletrônica Brasileira (TEB) composto por um circuito eletrônico ligado externamente a um notebook, e de um software instalado no disco rígido do computador. Os valores de duração do complexo QRS, intervalos PR e QT, comparados entre machos e fêmeas, apresentaram diferença significativa. Em milivoltagem a onda R foi o único parâmetro que apresentou diferença significativa entre machos e fêmeas. O peso dos animais também foi significativamente diferente entre os gêneros. O protocolo anestésico mostrou-se bem tolerado pelos animais deste experimento, não ocorrendo quadros de arritmias durante o tempo de monitoramento dos animais.(AU)

Influência de diferentes protocolos de contenção nosvalores do eletrocardiograma de macacos-da-noite (Aotus azarae infulatus) / Influence of different restraint protocols for the electrocardiogram values of feline night monkeys (Aotus azarae infulatus)

Macacos-da-noite são muito susceptíveis ao estresse e por isso a contenção química ou física deve ser cuidadosamente avaliada antes de qualquer procedimento. Protocolos anestésicos podem alterar alguns parâmetros fisiológicos, sendo o eletrocardiograma (ECG) um exame muito utilizado para avaliação do ritmo e da frequência cardíaca. O objetivo deste estudo foi avaliar a influência de quatro diferentes protocolos de contenção sobre o ECG realizado em Aotus azarae infulatus. Para isso foram utilizados 10 animais, machos, adultos, submetidos à contenção com a associação tiletamina/zolazepam (TZ), isoflurano (ISO), associação cetamina e midazolam (CET) e contenção física (CF). Não foram observadas diferenças nos parâmetros de ondas e complexos obtidos no ECG em todos os grupos testados, no entanto, durante a avaliação do traçado os animais do grupo CF apresentaram uma quantidade maior de alterações. Concluiu-se que os protocolos de contenção utilizados não alteraram os valores do ECG e que não foi possível considerar o grupo CF como controle devido causar mais alterações do que todos os protocolos testados.(AU)

Feline night monkeys are very susceptible to stress and therefore the physical or chemical restraint should be carefully evaluated before any procedure. Anesthetic protocols can alter some physiological parameters, and electrocardiogram (ECG) is a commonly exam used for evaluation of the rhythm and heart rate. The objective of this study was to evaluate the influence of four different protocols of restraining on ECG in Aotus azarae infulatus, in order to identify the best method of restraining in these primates. For that, we used 10 adult feline night monkeys, males, submitted to restraining protocols with the association tiletamine and zolazepam - (TZ), isoflurane (ISO), association ketamine and midazolam (CET) and physical restraint (CF). No differences were observed in the parameters wave and ECG complexes obtained in all groups tested; however, during the evaluation of the trace the animals of group CF showed a greater amount of change. It was concluded that the restraint protocols used did not change the values of the ECG, and it was not possible to consider the CF group as control due to more caused alterations than all other tested protocols.(AU)

Determination of eugenol in fish and shrimp muscle tissue by stable isotope dilution assay and solid-phase extraction coupled gas chromatography-triple quadrupole mass spectrometry.

In this study, we developed a new method for the accurate quantification of eugenol in fish samples based on stable isotope dilution assay (SIDA) and solid-phase extraction (SPE) coupled gas chromatography-triple quadrupole mass spectrometry (SIDA-SPE-GC-MS/MS). Due to the difference of matrix effect (ME), it was difficult to determine accurately the level of eugenol residue in different fish and shrimp samples based on external standard calibration method. SIDA was applied to compensate matrix effect (ME) that eugenol-d3 was used as internal standard (IS). Freshwater fish (carp, channel catfish), marine fish (turbot), and shrimp (Penaeus vannawei) were used for the method validation. The average recoveries of eugenol were in the range of 94.7 to 109.78 % when the spiking levels were 10, 50, and 200 µg kg(-1). The inter-day and intra-day precisions were in the range of 1.15-8.19 and 0.71-8.45 %. The limit of detection (LOD) and the limit of quantification (LOQ) were approximately 2.5 and 5.0 µg kg(-1). This method was applied to the real fish samples assay obtained from aquaculture markets in Beijing, China. Eugenol residue was found in two fish samples with the levels at 6.2 and 7.7 µg kg(-1), respectively. Graphical abstract Determination of eugenol in fish and shrimp muscle tissue.

Identification of Drugs in Parenteral Pharmaceutical Preparations from a Quality Assurance and a Diversion Program by Direct Analysis in Real-Time AccuTOFTM-Mass Spectrometry (DART-MS).

In healthcare settings drug diversion and impairment of physicians are major concerns requiring a rapid and efficient method for surveillance and detection. A Direct Analysis in Real Time ion source coupled to a JEOL AccuTOFTM time-of-flight mass spectrometer (DART-MS) method was developed to screen parenteral pharmaceutical formulations for potential drug diversion. Parenteral pharmaceutical formulations are also known as injectable formulations and are used with intravenous, subcutaneous, intramuscular and intra-articular administration. A library was created using the mass spectra data collected by a DART-MS operated in switching mode at 20, 60 and 90 V settings. This library contained 17 commonly encountered drugs in parenteral pharmaceutical formulations that included the surgical analgesic: fentanyl, hydromorphone and morphine; anesthetic: baclofen, bupivacaine, ketamine, midazolam, ropivacaine and succinylcholine; and a mixture of other drug classes: caffeine, clonidine, dexamethasone, ephedrine, heparin, methadone, oxytocin and phenylephrine. Randomly selected 200 de-identified parenteral pharmaceutical formulations containing one or more drugs were submitted for analysis to the FIRM Toxicology Laboratory at Virginia Commonwealth University Health and were screened using the DART-MS. The drug contents of the de-identified formulations were previously confirmed by a published high performance liquid chromatography (HPLC) method. The drugs in the formulations were rapidly and successfully identified using the generated library. The DART-MS and HPLC results were in complete agreement for all 200 parenteral pharmaceutical formulations.

Anesthetic constituents of Zanthoxylum bungeanum Maxim.: A pharmacokinetic study.

A sensitive and selective ultra high performance liquid chromatography with tandem mass spectrometry method was established and validated for the simultaneous determination of hydroxy-α-sanshool, hydroxy-ß-sanshool, and hydroxy-γ-sanshool in rat plasma after the subcutaneous and intravenous administration of an extract of the pericarp of Zanthoxylum bungeanum Maxim. Piperine was used as the internal standard. The analytes were extracted from rat plasma by liquid-liquid extraction with ethyl acetate and separated on a Thermo Hypersil GOLD C18 column (2.1 mm × 50 mm, 1.9 µm) with a gradient elution system at a flow rate of 0.4 mL/min. The mobile phase consisted of acetonitrile/0.05% formic acid in water and the total analysis time was 4 min. Positive electrospray ionization was performed using multiple reaction monitoring mode for the analytes. The calibration curves of the three analytes were linear over the tested concentration range. The intra- and interday precision was no more than 13.6%. Extraction recovery, matrix effect, and stability were satisfactory in rat plasma. The developed and validated method was suitable for the quantification of hydroxy-α-sanshool, hydroxy-ß-sanshool, and hydroxy-γ-sanshool and successfully applied to a pharmacokinetic study of these analytes after subcutaneous and intravenous administration to rats.

Effect of anesthetic, tag size, and surgeon experience on postsurgical recovering after implantation of electronic tags in a neotropical fish: Prochilodus lineatus (Valenciennes, 1837) (Characiformes: Prochilodontidae)

Implantation of telemetry transmitters in fish can be affected by different parameters. This study aimed to evaluate the effect of type of anesthetic, tag size, and surgeon experience on surgical and postsurgical wound healing in the neotropical fish Prochilodus lineatus . In total, eighty fish were surgically implanted with telemetry transmitters and forty fish were kept as controls. Forty fish were implanted with a small tag and other forty were implanted with a large tag. Similarly, forty fish were anesthetized with eugenol and forty fish were anesthetized by electroanesthesia, and forty surgeries were performed by an expert surgeon and forty surgeries were performed by novice surgeons. At the end of the experimental period seventeen (21.3%) tagged fish had postsurgical complications, including death (1.3%), tag expulsion (2.5%), antenna migration (2.5%), and infection (15%). Tag size was the key determinant for postsurgical complications. Surgical details and postsurgical wound healing were not affected by type of anesthetic. Incision size, duration of surgery, and wound area were significantly affected by tag size and surgeon experience, and the number of sutures was significantly affected by tag size only. The results indicate that successful implantation of telemetry transmitters is dependent upon surgeon experience and tag size.(AU)

A implantação de transmissores em peixes pode ser afetada por diversos aspectos. Este estudo objetivou avaliar a influência do tamanho do transmissor, do tipo de anestésico e da experiência do cirurgião em parâmetros cirúrgicos e recuperação pós-cirúrgica do peixe neotropical Prochilodus lineatus . Foram marcados oitenta indivíduos com transmissores de telemetria, enquanto outros quarenta foram utilizados como controle. Quarenta indivíduos foram marcados com um transmissor pequeno e outros quarenta com um transmissor maior. Foram utilizados dois tipos de anestésico sendo quarenta indivíduos anestesiados por eletronarcose e outros 40 por eugenol e as cirurgias foram realizadas por dois grupos de cirurgiões, experientes e inexperientes com quarenta peixes em cada grupo. Dezessete peixes (21,3%) apresentaram impactos diretos resultantes da cirurgia como o óbito (1,3%), perda do transmissor (2,5%), migração da antena (2,5%) e infecções internas (15%). Estes efeitos estão ligados ao tamanho do transmissor utilizado. A experiência do cirurgião possui relação direta em três parâmetros cirúrgicos (tamanho da incisão, tempo de cirurgia e área de cicatrização). O tamanho dos transmissores utilizados possui relação com quatro parâmetros (tamanho da incisão cirúrgica, número de suturas utilizadas, tempo de cirurgia e área de cicatrização). O anestésico não teve relação com os parâmetros cirúrgicos. Os resultados indicam que tanto a dimensão dos transmissores quanto a experiência dos cirurgiões têm impacto direto no sucesso de implantação dos transmissores.(AU)

Separation and enhanced detection of anesthetic compounds using solid phase micro-extraction (SPME)-Raman spectroscopy.

Polydimethylsiloxane (PDMS)-based solid-phase micro-extraction (SPME) was used along with Raman spectroscopy (RS) to separate and enhance the detection of five anesthetic compounds (halothane, propofol, isoflurane, enflurane, and etomidate) from aqueous and serum phases. Raman signals in the spectral ranges 250-450 cm(-1) and 950-1050 cm(-1) allowed the unique characterization of all five compounds when extracted into the PDMS phase. The SPME-RS detection of clinically relevant concentrations of aqueous propofol (6.5 µM) and halothane (200 µM) is shown. We quantify the partition coefficient for aqueous halothane in PDMS as log K = 1.9 ± 0.2. Solid-phase micro-extraction of the anesthetics makes their detection possible without the strong autofluorescent interference of serum proteins. Because of low solubility and/or weak Raman scattering, we found it challenging to detect enflurane, isoflurane, and etomidate directly from the aqueous phase, but could we do so with SPME enhancement. These studies show the potential of SPME-RS as a method for the direct detection of anesthetics in blood.

Determination of levels of current drugs in hospital and urban wastewater.

A rapid, sensitive and highly specific HPLC-MS/MS method with direct on-line preparation was applied for the determination of 20 common pharmaceuticals in hospital and urban wastewater. Median drug concentrations were quite similar in the majority of samples, cerca 1 µg L⁻¹ ranging from 0.06 to 2.67 µg L⁻¹ in both water. Pharmaceutical hospital contribution, below 1 %, was negligible, as compared to the huge amount in the municipal plant flow. Due to only partial elimination in the plant, hundreds of kilograms of harmful waste per year are discharged in the River Seine. Therefore, to reduce potential human and environmental exposure, a topic of major concern, an efficient drug treatment procedure should be used at the municipal plant stage in order to reduce urban wastewater pollution. The HPLC-MS/MS method could be a very useful tool to optimize the pharmaceutical wastewater treatment process.