Simultaneous analysis of oxytetracycline hydrochloride, lidocaine, and bromhexine hydrochloride in the presence of many interfering excipients.

A gradient elution high-performance liquid chromatographic method with a diode array detector is introduced for the first time for the simultaneous estimation of three drugs, namely, oxytetracycline hydrochloride (OXT), lidocaine (LDC), and bromhexine hydrochloride (BRH), in a veterinary formulation (OxyClear® solution) that contains many interfering additives. The method used a C-8 column. The chromatographic eluting solution included acidified water (0.1% trifluoroacetic acid in water) and acetonitrile at a 1-ml/min flow rate and 254 nm as a nominated detection wavelength. The chromatographic process was assessed in terms of linearity, precision, accuracy, LOD, and LOQ. OXT, LDC, and BRH were linear in the range of 1-60, 5-100, and 1-60 µg/ml, respectively. The three drugs were determined successfully without the interference of three excipients having UV absorbances. Furthermore, the purities of the peaks of the three drugs were confirmed by comparing the UV spectra of investigated peaks to the UV reference spectra in Clarke's Analysis of Drugs and Poisons. The greenness value of the method was 0.69 with a faint green-colored pictogram using the AGREE tool. These merits recommend the application of the planned method in QC laboratories for purity testing and concentration assays for the pure drugs and commercial formulations.

Voltammetry of local anesthetics: theoretical and practical aspects.

Local anesthetics (LAs) are widely used in anesthesiology, ophthalmology, and otolaryngology as well as for treatment of chronic and oncological pain. However, anesthetics can cause adverse effects up to lethal ones. In this work, we cited reviews on chromatographic and spectroscopic methods of local anesthetics determination published earlier, and the main purpose was to review the possibilities and advantages of voltammetric methods used for the LAs determination. The electrochemical behavior, mechanism of LAs transformation on the various working electrodes and analytical parameters of voltammetric methods used for their determination were reviewed in the work. Vast majority of these methods were developed for the most widely used anesthetics in medicine like benzocaine, lidocaine and procaine. Special attention was paid to possible mechanisms of electrochemical oxidation and in some cases reduction of LAs or their derivatives. Voltammetry is used for the determination of LAs in pharmaceutical formulations and in biological fluids. The analytical characteristics in terms of sensitivity, selectivity, reproducibility also were discussed in the article.

Dispersão da lidocaína administrada por via epidural em cães posicionados em decúbito lateral ou esternal / [Dispersion of lidocaine epidurally administered to dogs positioned on lateral or external decubitus]

O objetivo do estudo foi verificar clinicamente a dispersão da lidocaína no espaço epidural de cães posicionados em diferentes decúbitos. Foram utilizados 16 cães, com peso médio de 17,5 quilogramas. Esses foram tranquilizados com acepromazina, anestesiados com propofol e alocados em dois grupos, conforme o decúbito de posicionamento: decúbito esternal (GE) e decúbito lateral direito (GLD). Ambos os grupos receberam lidocaína a 2%, no volume de 0,25mL/kg, e permaneceram no mesmo decúbito por 20 minutos. Em seguida, avaliou-se o bloqueio dos membros pélvicos e a extensão do bloqueio, a partir da sétima vértebra lombar, por meio de pinçamento interdigital e do panículo paravertebral. Foi, então, realizada cirurgia de orquiectomia. Após tal procedimento, avaliou-se o tempo total de bloqueio dos membros pélvicos. Todos os cães apresentaram bloqueio bilateral, sem diferenças quanto à extensão cranial entre os grupos, sendo a mediana de 7,5 (1-14) vértebras para GE e de 4 (1-14) para GLD. O tempo de bloqueio dos membros direito e esquerdo foi de 123 ± 26 e 130 ± 20 minutos, para GE, e de 120 ± 21 e 121 ± 20 minutos, para GLD, sem diferenças entre os grupos ou entre os membros. Conclui-se que o decúbito não interfere na distribuição da lidocaína administrada por via epidural.(AU)

The aim of this study was to clinically verify the dispersion of lidocaine in the epidural space of dogs placed in different positions. Sixteen dogs with an average weight of 17.5 kilograms were used. These were tranquilized with acepromazine, anesthetized with propofol and allocated to two groups: sternal decubitus (GE) and right lateral decubitus (GLD). Both groups received 2% of lidocaine in the volume of 0.25mL/kg and remained in the same position for 20 minutes. The blocking of the pelvic limbs and the extension of it from the seventh lumbar vertebra were evaluated by means of interdigital and paravertebral panniculus clamping. Orchiectomy surgery was then performed. Afterwards, the total blocking time of the pelvic limbs was evaluated. All dogs presented bilateral blocking, with no differences in cranial extension between groups, with a median of 7.5 (1-14) vertebrae for GE and 4 (1-14) for GLD. The blocking time of the right and left limbs were 123 ± 26 and 130 ± 20 minutes for GE, and 120 ± 21 and 121 ± 20 minutes for GLD with no difference between groups or between limbs. It is concluded that the decubitus does not interfere with the epidural lidocaine distribution.(AU)

Bloqueio motor e sensitivo da lidocaína ou da ropivacaína peridural em cães / [Motor and sensitive blockade provided by epidural lidocaine or ropivacaine in dogs]

Objetivou-se avaliar o bloqueio sensitivo e motor da administração peridural de 0,2mL/kg de duas concentrações de ropivacaína em comparação à lidocaína em cães. Utilizaram-se 24 cães, distribuídos em quatro grupos: NaCl a 0,9% (GS), lidocaína a 2% (GL), ropivacaína a 0,5% (GR5) e ropivacaína a 0,75% (GR7,5). Avaliaram-se a presença de movimentação espontânea, deambulação, sensibilidade superficial e profunda nos momentos cinco, 10, 15, 20, 25, 30, 45, 60, 90, 120, 180, 240 e 300 minutos após peridural. O retorno à movimentação espontânea foi semelhante entre GL (42,50 ± 6,12) e GR7,5 (69,2 ± 58,9). O tempo para deambulação foi mais prolongado em GR7,5 (107,5 ± 79,3) que em GS (9,2 ± 3,8) e em GR5 (32,5 ± 20,9). O retorno da sensibilidade profunda foi maior em GR 7,5 (152,5 ± 89,2) que em GS (5,8 ± 2,0), GR5 (46,7 ± 46,3) e GL (52,5 ± 20,7). O tempo de retorno da sensibilidade superficial foi maior em GR7,5 (205,0 ± 129,3) que em GS (7,5 ± 2,7), GL (72,5 ± 19,9) e GR5 (97,5 ± 55,1). Apesar do retorno precoce da movimentação, ropivacaína 0,75% está relacionada a tempo prolongado de recuperação da função muscular e bloqueio sensitivo mais prolongado que lidocaína e ropivacaína 0,5%.(AU)

The aim of the present study was to evaluate the sensory and motor blockade of epidural 0.5% and 0.75% Ropivacaine or Lidocaine in dogs. Twenty-four dogs were distributed in four groups: 0.9% NaCl (GS), 2% lidocaine (GL), 0.5% ropivacaine (GR5) and 0.75% ropivacaine (GR7.5). Spontaneous movement, ability to walk, superficial, and deep pain response were assessed 5, 10, 15, 20, 25, 30, 45, 60, 90, 120, 180, 240 and 300 minutes after epidural. Time to return to spontaneous movement was similar between GL (42.50 ± 6.12) and GR7.5 (69.2 ± 58.9). Time to return to ambulation was longer in GR7.5 (107.5 ± 79.3) than in GS (9.2 ± 3.8) and GR5 (32.5 ± 20.9). Time to recover deep sensitivity was longer in GR 7.5 (152.5 ± 89.2) than in GS (5.8 ± 2.0), GR5 (46.7 ± 46.3) and GL (52.5 ± 20.7). Time to return superficial sensitivity was longer in GR7.5 (205.0 ± 129.3) when compared to GS (7.5 ± 2.7), GL (72.5 ± 19.9) and GR5 (97.5 ± 55.1). Despite the early return of spontaneous movement, 0.75% ropivacaine is related to longer periods for muscle function recovery and longer sensory block than lidocaine and 0.5% ropivacaine.(AU)

A novel LC-MS/MS analytical method for detection of articaine and mepivacaine in blood and its application to a preliminary pharmacokinetic study.

Local anaesthetics (LAs) are commonly used in surgery, especially in dentistry. They cause a transitory inhibition of nerve signal due to the blockade of the voltage-gated sodium channels. LAs are administrated alone or with vasoconstriction agents, such as adrenaline. Toxicity of LAs is associated to neurological and cardiovascular alterations. Tachycardia, arrhythmia, tremors, tonic-clonic seizure and respiratory depression (at high doses) are the main symptoms of intoxication by LAs. Lidocaine, articaine and mepivacaine are among the most used anaesthetics. This study aimed to fully validated a new method for the simultaneous detection of articaine and mepivacaine in whole blood. Sample treatment consisted in a liquid-liquid extraction with phosphate buffer (pH 8, 0.1 M) and ethyl-acetate. Analysis was performed by liquid chromatography-tandem mass spectrometry in multiple reaction monitoring mode (transitions: articaine, 285→8658 m/z; mepivacaine, 247→9870 m/z; lidocaine - internal standard -, 235→8658 m/z). The method proved to be highly sensitive with limit of quantifications for articaine and mepivacaine of 0.8 and 0.1 ng/mL, respectively. Accuracy and precision were always within the acceptance criteria. The new procedure was also successfully applied to a preliminary pharmacokinetics study.

The Oral Administration of Lidocaine HCl Biodegradable Microspheres: Formulation and Optimization.

PURPOSE: Lidocaine (LID) is a local anesthetic that is administered either by injection and/or a topical/transdermal route. However, there is a current need to develop efficacious methods for the oral delivery of LID with optimized bioavailability. METHODS: We developed oral LID biodegradable microspheres that were loaded with alginate-chitosan with different mass ratios, and characterized these microspheres in vitro. We also developed, and utilized, a simple and sensitive HPLC-tandem mass spectrometry (LC-MS-MS) method for assaying LID microspheres. RESULTS: The mean particle size (MPS) of the LID microspheres ranged from 340.7 to 528.3 nm. As the concentration of alginate was reduced, there was a significant reduction in MPS. However, there was no significant change in drug entrapment efficiency (DEE), or drug yield, when the alginate concentration was either increased or decreased. DSC measurements demonstrated the successful loading of LID to the new formulations. After a slow initial release, less than 10% of the LID was released in vitro within 4 h at pH 1.2. In order to evaluate nephrotoxicity, we carried out MTT assays of LID in two types of cell line (LLC-PK1 and MDCK). LID significantly suppressed the cell toxicity of both cell lines at the concentrations tested (100, 200, and 400ng/µL). CONCLUSION: Experiments involving the oral delivery of LID formulations showed a significant reduction in particle size and an improvement in dissolution rate. The formulations of LID developed exhibit significantly less toxicity than LID alone.

Sterility and concentration of liposomal bupivacaine single-use vial when used in a multiple-dose manner.

OBJECTIVE: To evaluate the sterility of bupivacaine liposome injectable suspension (Nocita®) used in a multiple-dose fashion for 5 days. STUDY DESIGN: Triplicate liposomal bupivacaine vials were stored under two conditions, (1) room temperature (24°C) and (2) refrigerated temperature (5°C). A 3-mL aliquot was withdrawn from each vial daily. Samples were inoculated in tryptic soy broth in triplicate and then incubated for 24 hours at 37°C and subcultured every 48 hours onto blood agar and Sabouraud dextrose agar, respectively. Separate 1.5-mL aliquots of liposomal bupivacaine were centrifuged at 3500 g to separate liposome-encapsulated bupivacaine from the solution. Concentration of unencapsulated bupivacaine was analyzed via high-pressure liquid chromatography. Data were analyzed by using mixed effects procedure with multiple comparisons. SAMPLE POPULATION: Ten 20-mL vials of bupivacaine liposome injectable suspension stored under two conditions, (1) room temperature (24°C) and (2) refrigerated temperature (5°C). RESULTS: Five days of repeated withdrawal from the single-use vials yielded no bacterial growth. One control vial, which was opened and punctured once on the last day of the experiment, yielded fungal growth of an Aspergillus spp, likely an environmental contaminant. The concentration of free bupivacaine did not significantly differ until the fifth day of sampling. CONCLUSION: When aseptic technique was used, liposomal bupivacaine remained sterile for 5 days. Concentrations of free bupivacaine were unchanged from baseline for 4 days in both refrigerated and room temperature conditions. CLINICAL SIGNIFICANCE: Single-use liposomal bupivacaine vials can be used extralabel in a multiple-dose fashion for up to 4 days when stored either refrigerated or room temperature when sterile technique is used.

Selective extraction of cocaine from biological samples with a miniaturized monolithic molecularly imprinted polymer and on-line analysis in nano-liquid chromatography.

We report the on-line coupling of a monolithic molecularly imprinted polymer to nano-liquid chromatography for the selective analysis of cocaine and its main metabolite, benzoylecgonine, in complex biological samples. After the screening of different synthesis conditions, a monolithic molecularly imprinted polymer was in situ synthesized into a 100 µm internal diameter fused-silica capillary using cocaine as template, methacrylic acid as functional monomer, and trimethylolpropane trimethacrylate as cross-linker. Scanning electron microscopy was used to assess the homogeneous morphology of the molecularly imprinted polymer and its permeability was measured. Its selectivity was evaluated by nano-liquid chromatography-ultraviolet, leading to imprinting factors of 3.2 ±â€¯0.5 and 2.2 ±â€¯0.3 for cocaine and benzoylecgonine, respectively, on polymers resulting from three independent syntheses, showing the high selectivity and the repeatability of the synthesis. After optimizing the extraction protocol to promote selectivity, the monolithic molecularly imprinted polymer was successfully on-line coupled with nano-liquid chromatography-ultraviolet for the direct extraction and analysis of cocaine present in spiked human plasma and saliva samples. The repeatability of the obtained extraction recovery, between 85.4 and 98.7% for a plasma sample spiked at 100 ng mL-1, was high with relative standard deviation values lower than 5.8% for triplicate analyses on each of the three independently synthesized molecularly imprinted polymers. A linear calibration range was achieved between 100 and 2000 ng mL-1 (R2 = 0.999). Limits of quantification of 14.5 ng mL-1 and 6.1 ng mL-1 were achieved in plasma and urine samples, respectively. The very clean-baseline of the resulting chromatogram illustrated the high selectivity brought by the monolithic molecularly imprinted polymer that allows the removal of a huge peak corresponding to the elution of interfering compounds and the easy determination of the target analyte in these complex biological samples.

A systematic investigation of forensic hair decontamination procedures and their limitations.

The effectiveness of decontamination procedures used for the removal of external drug contamination in forensic hair analysis is an ongoing debate. This investigation evaluated wash methods complying with Society of Hair Testing (SoHT) guidelines and their capacity to remove cocaine (COC) and methamphetamine (MA) from artificially contaminated hair. The most effective decontamination method was determined using a systematic approach, involving (1) an initial washing solvent screen, (2) optimization of wash duration, (3) comparison of sequential wash methods, and (4) reanalysis of clinical hair samples. For analysis, hair was subjected to micro-pulverized methanolic extraction prior to quantitation by ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS). Methanol (MeOH) and 0.1 M phosphate buffer (pH 6) were the most effective organic and aqueous solvents, respectively, removing 28%-38% of COC and 16%-31% of MA. Wash durations longer than 30-60 minutes did not remove additional amounts, and a more efficient sequential wash method was subsequently developed. Despite this, the interpretation of reportable results relative to the SoHT cut-off levels was unchanged for most clinical hair samples reanalyzed after washing by agitation for 30 minutes with MeOH. These findings highlight the inability of decontamination solvents to completely remove external COC and MA contamination from hair, including wash methods adhering to SoHT guidelines.

Pre-analytical considerations of condom traces: A review of composition, background, transfer and persistence.

Today, rape and sexual assault cases are mainly solved using evidence such as medical evidence or DNA analysis. Condom traces have been found to be present in 10% of assaulted women, when no DNA is found [1]. Numerous studies have emphasized the interest of analysing the composition of male condoms and their traces, and developing specific methods for the analysis of this type of evidence. However, transfer and persistence of condom traces in a specific matrix are rarely referenced. Therefore, forensic scientists have no complete knowledge of the trace and what could be expected in a real case. The purpose of this article is to review the literature addressing the composition of condoms and their traces as well as its influence on the transfer and persistence from a forensic point of view. Peer-reviewed literature, patents, professional literature, data from international administrations and international organisations' reports have been used to track the composition and the problematics of transfer and persistence of condom traces. The results of this review show that the composition of male condoms and their traces are complex systems, with numerous compounds originating from the condom at the moment of the transfer and evolving over time according to specific persistence patterns. Although numerous types of analyses have already been proposed and tested for condom traces, forensic evidence considerations have not been fully studied yet. Considering the fact that sexual assaults without the detection of DNA are increasingly frequent, there is a definite medical and forensic need to improve our knowledge of the processes involved in the development of condom traces in order to better understand analytical results.

Theoretical Investigation of Design Space for Multi Layer Drug Eluting Bioresorbable Suture Threads.

BACKGROUND: The work presented here is focused on the development of a comprehensive theoretical model for the description of drug release from a double - layer bioresorbable suture thread and the therapeutic efficacy of the active compounds delivered in the surrounding tissue. METHODS: In particular, the system under investigation is composed of a core of slow-degrading polylactic- acid-co-ε-caprolactone (PLCL), where an antibiotic compound (Vancomycin) is loaded, surrounded by a shell of a fast-degrading polylactic-co-glycolic acid (PLGA) which contains an anesthetic drug (Lidocaine hydrochloride) for the post-surgical pain relief. RESULTS: This system is of potential interest for the combined effects provided by the different active molecules, but the different release and polymer degradation dynamics, as well as their mutual influence, do not allow an intuitive a priori evaluation of device behavior, which can be rationalized through mathematical modeling. The model takes into account the main involved phenomena (polymer degradation and diffusion of the drugs within the device and the tissue, where they are metabolized) and their synergic effects on the overall system behavior. CONCLUSION: Model results are discussed in order to quantify the impact of the main design parameters on device performances, thanks to the use of phase diagrams (which show drug effect in time and space) whose insights are summarized in order to determine a design space according to the specific needs.

Estimation of day of death using micro-segmental hair analysis based on drug use history: a case of lidocaine use as a marker.

During investigations of unnatural death, the time of death is generally estimated using anatomical examinations. However, it can be difficult to accurately determine the day of death, because postmortem changes in the body tissues can be greatly affected by the circumstances of the location of the corpse. We recently developed a method to estimate the day of drug ingestion, using micro-segmental hair analysis based on internal temporal markers (ITMs). In this method, ITMs are ingested at a specific time interval before hair collection to mark timescales within individual hair strands. A single hair strand is segmented at 0.4-mm intervals, corresponding to average daily hair growth. The day of drug ingestion is eventually estimated by calculating the distances between segments containing the drug and ITMs in a hair strand. In the present study, the method was applied to estimate the day of death. A corpse was discovered with a documented medical history of lidocaine administration for surgery 57 days before the discovery. Micro-segmental analysis of a hair plucked from the corpse was performed using lidocaine as an ITM. Lidocaine was detected at specific regions in the hair strands. The day of death was estimated using the known surgery day, the distance from the hair root to the lidocaine peak in the hair strand, and the average hair growth rate. The novel estimation method using a hair enabled us to narrow the estimated time range of death up to the day of death, unlike the conventional anatomical examination. The micro-segmental hair analysis based on drug use history can be extremely helpful in determining the time of an unnatural death.

Reduced graphene oxide as an efficient sorbent in microextraction by packed sorbent: Determination of local anesthetics in human plasma and saliva samples utilizing liquid chromatography-tandem mass spectrometry.

Herein, reduced graphene oxide (RGO) has been utilized as an efficient sorbent in microextraction by packed sorbent (MEPS). The combination of MEPS and liquid chromatography-tandem mass spectrometry has been used to develop a method for the extraction and determination of three local anesthetics (i.e. lidocaine, prilocaine, and ropivacaine) in human plasma and saliva samples. The results showed that the utilization of RGO in MEPS could minimize the matrix effect so that no interfering peaks at the retention times of the analytes or internal standard was observed. The high extraction efficiency of this method was approved by mean recoveries of 97.26-106.83% and 95.21-105.83% for the studied analytes in plasma and saliva samples, respectively. Intra- and inter-day accuracies and precisions for all analytes were in good accordance with the international regulations. The accuracy values (as percentage deviation from the nominal value) of the quality control samples were between -2.1 to 13.9 for lidocaine, -4.2 to 11.0 for prilocaine and between -4.5 to -2.4 for ropivacaine in plasma samples while the values were ranged from -4.6 to 1.6 for lidocaine, from -4.2 to 15.5 for prilocaine and from -3.3 to -2.3 for ropivacaine in human saliva samples. Lower and upper limit of quantification (LLOQ, ULOQ) were set at 5 and 2000 nmol L-1 for all of the studied drugs. The correlation coefficients values were ≥0.995. The limit of detection values were obtained 4 nmol L-1 for lidocaine and prilocaine, and 2 nmol L-1 for ropivacaine.

Rapid characterization of cocaine in illicit drug samples by 1D and 2D NMR spectroscopy.

Seized samples of illegally produced cocaine have a very large variability in composition; a fact that may result in a challenge to their analysis. We demonstrate here a simple and fast method to detect the presence of cocaine in both hydrochloride and free-base forms in illicit drug samples by nuclear magnetic resonance (NMR) spectroscopy. This is achieved by combining the commonly used 1D spectra and diffusion-ordered spectroscopy and introducing the 2D maximum-quantum NMR approach to forensic analysis. The protocol allows the facile determination of the cocaine forms even in the presence of multiple adulterants. By relying on non-uniform sampling acceleration of 2D spectroscopy, the identification can be obtained in less than 3 min for 10 mg of product. Moreover, we show that intermolecular interactions of the sample constituents, while affecting the analysis result, do not interfere with the quality of the detection of the proposed protocol.

Identification and Quantification of Cocaine and Active Adulterants in Coca-Paste Seized Samples: Useful Scientific Support to Health Care.

Adulteration is a common practice in the illicit drugs market, but the psychoactive and toxic effects provided by adulterants are clinically underestimated. Coca-paste (CP) is a smokable form of cocaine which has an extremely high abuse liability. CP seized samples are sold adulterated; however, qualitative and quantitative data of CP adulteration in forensic literature is still scarce. Besides, it is unknown if adulterants remain stable when CP is heated. This study was designed to report the chemical content of an extensive series of CP seized samples and to demonstrate the stability (i.e., chemical integrity) of the adulterants heated. To achieve this goal, the following strategies were applied: (1) a CP adulterated sample was heated and its fume was chemically analyzed; (2) the vapor of isolated adulterants were analyzed after heating; (3) plasma levels of animals exposed to CP and adulterants were measured. Ninety percent of CP seized samples were adulterated. Adulteration was dominated by phenacetin and caffeine and much less by other compounds (i.e., aminopyrine, levamisole, benzocaine). In the majority of CP analyzed samples, both cocaine and caffeine content was 30%, phenacetin 20% and the combination of these three components reached 90%. Typical cocaine pyrolysis compounds (i.e., BA, CMCHTs, and AEME) were observed in the volatilized cocaine and CP sample but no pyrolysis compounds were found after isolated adulterants heating. Cocaine, phenacetin, and caffeine were detected in plasma. We provide current forensic data about CP seized samples and demonstrated the chemical integrity of their adulterants heated.

Combination of Transversus abdominis plane block and Serratus plane block anesthesia in dogs submitted to masctetomy / Combinação dos bloqueios anestésicos do plano transverso abdominal e do plano serrátil em cadelas submetidas à mastectomia

This paper pretends to demonstrate the effect of the combination of transversus abdominis plane block (TAP block) and Serratus plane block (SP block) techniques in analgesia of 4 dogs undergoing total unilateral mastectomy. Dogs were premedicated with methadone (0.5mg.kg-1) intramuscularly. Anesthesia was induced with propofol (6mg.kg-1) and midazolam (0.3mg.kg-1) and maintained with isoflurane. SP and TAP block were performed unilaterally using ultrasound by the injection of bupivacaine 0.25% (0.3mL kg-1) diluted with NaCl solution 1:1. Heart rate (HR), respiratory rate (f), non-invasive arterial pressure, esophageal temperature (T), oxygen saturation (SpO2) and electrocardiogram were monitored continuously. Animals were monitored for two and four hours after extubation for pain by using the Canine Acute Pain Scale from Colorado State University. Two hours after extubation, tramadol (4mg.kg-1) and dipyrone (25mg.kg-1) was administered to all dogs. It was not observed any alteration on cardiac rhythm. HR, f, T and mean arterial pressure remained below the preincisional values for all dogs. No dog required intraoperative rescue analgesia. Recovery from anesthesia was without any complication. All animals scored 0 (0/5) at pain scale, two and four hours after extubation and none of them expressed concern over the surgical wound. Dogs were able to walk before two hours after extubation. The combination of both techniques is effective in anesthetic blocking the thoracic and abdominal walls and it is suggested both may be included in the multimodal analgesia protocols for this type of surgery.(AU)

Este trabalho pretende demonstrar o efeito analgésico da combinação das técnicas de bloqueio do plano transverso abdominal (TAP block) e bloqueio do plano serrátil (SP block) em 4 cadelas submetidas à mastectomia unilateral total. Os animais foram pré-medicados com metadona (0,5mg.kg-1) por via intramuscular. A anestesia foi induzida com propofol (6mg.kg-1) e midazolam (0,3mg.kg-1) e mantida com isoflurano. Os bloqueios SP e TAP foram realizados unilateralmente, utilizando ultrassonografia, pela injeção de bupivacaína a 0,25% (0,3mL.kg-1), diluída com solução de NaCl a 1:1. A frequência cardíaca (FC), frequência respiratória (f), pressão arterial não invasiva, temperatura esofágica (T), saturação de oxigênio (SpO2) e eletrocardiograma foram monitorados continuamente. Os animais foram monitorizados durante duras e quatro horas após a extubação para a dor usando a Escala de Dor Aguda Canina da Universidade Estadual do Colorado. Duas horas após a extubação, tramadol (4mg.kg-1) e dipirona (25mg.kg-1) foram administrados a todos os cães. Não foi observada qualquer alteração no ritmo cardíaco. HR, f, T e pressão arterial média permaneceram abaixo dos valores basais para todos os cães. Nenhum cão requereu resgate analgésico intra-operatório. Não houve complicações na recuperação anestésica. Todos os animais apresentaram escore 0 (0/5) na escala de dor, duras e 4 quatro horas após a extubação e nenhum expressou desconforto com a ferida cirúrgica. Todos os cães foram capazes de caminhar antes de duas horas após extubação. A combinação de ambas as técnicas é eficaz no bloqueio anestésico das paredes torácica e abdominal e sugere-se que ambos podem ser incluídos nos protocolos de analgesia multimodal para este tipo de cirurgia.(AU)

Response of three digital anesthetic technics in horses with forelimb hoof lameness / Resposta de três técnicas anestésicas digitais em equinos com claudicação dos membros anteriores ligada ao casco

The presented study aimed to assess objectively the response of distal interphalangeal joint (DIJ), navicular bursa (NB) and deep digital flexor tendon sheath (DDFTS) anesthesia in horses with forelimb hoof lameness; and evaluate if the presence of radiographic abnormalities on navicular bone could interfere on blocks' results. Fifteen horses with lameness improvement above 70% after palmar digital nerve (PDN) block were selected for this study. Blocks were assessed separately on five consecutive trials at seven different time-points. The fifth trial was performed to evaluate the influence of exercise on preexisting lameness. Most of horses (73.33%) presented pain related to the podotrochlear apparatus based on clinical and lameness exam and blocks' responses. NB and DIJ anesthesia differed on the frequency of horses with lameness improvement above 70% only at 10min (p=0.03), and both differed from DDFTS block until 30'(p<0.05). The blocks' response was variable along the time and the highest means for NB, DIJ and DDFTS were observed at 5-10 minutes ('), 15-20' and 10-15' respectively.Exercise had low interference on lameness intensity since no improvement above 50% was observed and an increase on lameness intensity over time was identified in seven horses. Variable grades of navicular bone radiographic lesions were observed in 14 horses, although these lesions had no interference on blocks' response (p>0.05). The NB and DIJ blocks had similar responses and both were superior to DDFTS anesthesia, coincident with a major prevalence of podotroclear apparatus abnormalities in this equine population.(AU)

O presente estudo avaliou, de forma objetiva, as respostas do bloqueio da articulação interfalangeana distal (AID), da bursa do navicular (BN) e da bainha do tendão flexor digital profundo (BTFDP) em equinos com claudicação ligada ao casco nos membros torácicos; além de analisar a influência das alterações radiográficas do osso navicular no resultado dos bloqueios. Quinze cavalos, que apresentaram uma melhora da claudicação acima de 70% após o bloqueio do nervo digital palmar, foram selecionados para este estudo. Os bloqueios foram avaliados separadamente em cinco turnos consecutivos e em sete tempos diferentes. O quinto turno foi utilizado para analisar a influência do exercício sobre a claudicação preexistente. A maioria dos cavalos (73,33%) apresentou dor relacionada à porção palmar do casco, com base nos achados do exame clínico em movimento e nas respostas dos bloqueios. As anestesias da BN e da AID apresentaram diferença quanto à frequência de cavalos com melhora da claudicação acima de 70% apenas aos 10min (p=0.03), e ambos diferiram do bloqueio da BTFDP até os 30min (p<0.05). A resposta dos bloqueios foi variada ao longo do tempo, e as maiores médias de melhora da claudicação para os bloqueios BN, AID e BTFDP foram observadas aos 5-10min, 15-20min e 10-15min, respectivamente. O exercício teve pequena interferência na intensidade da claudicação, uma vez que nenhuma melhora acima de 50% foi observada e sete cavalos aumentaram a intensidade da claudicação ao longo do tempo. A presença de diferentes graus de lesão radiográfica do osso navicular foi observada em 14 cavalos, porém essas lesões não interferiram na resposta dos bloqueios (p>0,05). Os bloqueios da BN e da AID apresentaram respostas semelhantes, e ambos foram superiores ao bloqueio da BTFDP, coincidindo com uma marcada prevalência de doença do aparato podotroclear nesta população de equinos.(AU)

Probing the dynamics of complexed local anesthetics via neutron scattering spectroscopy and DFT calculations.

Since potential changes in the dynamics and mobility of drugs upon complexation for delivery may affect their ultimate efficacy, we have investigated the dynamics of two local anesthetic molecules, bupivacaine (BVC, C18H28N2O) and ropivacaine (RVC, C17H26N2O), in both their crystalline forms and complexed with water-soluble oligosaccharide 2-hydroxypropyl-ß-cyclodextrin (HP-ß-CD). The study was carried out by neutron scattering spectroscopy, along with thermal analysis, and density functional theory computation. Mean square displacements suggest that RVC may be less flexible in crystalline form than BVC, but both molecules exhibit very similar dynamics when confined in HP-ß-CD. The use of vibrational analysis by density functional theory (DFT) made possible the identification of molecular modes that are most affected in both molecules by insertion into HP-ß-CD, namely those of the piperidine rings and methyl groups. Nonetheless, the somewhat greater structure in the vibrational spectrum at room temperature of complexed RVC than that of BVC, suggests that the effects of complexation are more severe for the latter. This unique approach to the molecular level study of encapsulated drugs should lead to deeper understanding of their mobility and the respective release dynamics.

Eficácia e efeitos hemodinâmicos da anestesia raquidiana com ropivacaína isobárica, hipobárica ou hiperbárica em cães anestesiados com isofluorano / Efficacy and hemodynamic effects of spinal anesthesia with isobaric, hypobaric or hyperbaric ropivacaine in dogs anesthetized with isoflurane

O presente estudo objetivou avaliar a anestesia raquidiana com ropivacaína em cães alterando a baricidade do anestésico local, investigando as alterações hemodinâmicas e complicações. Foram utilizados seis cães, Beagle, 4 anos, submetidos a anestesia inalatória com isofluorano e aos tratamentos: Ghipo = anestesia raquidiana hipobárica (0,5 mL NaCl 0,9% + 0,5 mL ropivacaína 0,75%); Giso = anestesia raquidiana isobárica (0,5 mL NaCl 1,53% + 0,5 mL ropivacaína 0,75%); Ghiper = anestesia raquidiana hiperbárica (0,5 mL glicose 10% + 0,5 mL ropivacaína 0,75%). Após indução anestésica e manutenção com isofluorano, os animais foram posicionados em decúbito lateral direito para a passagem de um cateter de artéria pulmonar pela veia jugular esquerda. Após esse procedimento, a punção subaracnóide foi realizada entre L5-L6 com uma agulha espinhal 22G, seguida da administração de 1 mL de anestésico local em 1 min. Os animais foram mantidos por 60 minutos anestesiados em decúbito ventral. A FC, f, PAM, DC, PAPm e TºC apresentaram aumento progressivo em todos os grupos enquanto que a PCPm, apenas no GHIPO, aumentou ao longo de todos os momentos. O IRPT no GISO apresentou valores significativamente superiores no M1, M5 e M10 comparado aos demais grupos, exceto no M5, em que o GISO diferiu somente do GHIPER. O IRVP no GISO aumentou no M5 em comparação ao MB. Foram observados efeitos adversos como déficit motor unilateral, atonia vesical, excitação, dor aguda e quemose. De acordo com os dados obtidos no presente estudo pode-se concluir que os animais que receberam anestesia raquidiana com as soluções hiperbárica e isobárica apresentaram maior bloqueio motor comprovando que a baricidade influencia diretamente o tipo de fibra a ser bloqueada. A utilização de solução isobárica resulta em um bloqueio misto (motor e sensitivo). As alterações hemodinâmicas descritas na literatura como, bradicardia e hipotensão, não puderam ser evidenciadas neste estudo embora o volume de anestésico tenha sido baixo associado a influência dos efeitos do isofluorano. Em relação às complicações evidenciadas, sugere-se acompanhamento pós-anestésico dos animais submetidos à anestesia raquidiana a fim de que quaisquer alterações possam ser identificadas precocemente e tratadas.(AU)

The aim of the study was to assess hemodynamic changes and complications of spinal anesthesia with ropivacaine at different baricities. Six beagle dogs aged four years. The dogs were anesthetized with isoflurane and subjected to the following treatments: Ghypo = spinal anesthesia with hypobaric ropivacaine (0.5mL of 0.9% NaCl+0.5mL ropivacaine at 0.75%); Giso = isobaric spinal anesthesia (0.5mL of 0,906% NaCl+0.5mL ropivacaine at 0.75%); Ghyper = hyperbaric spinal anesthesia (0.5mL of 10% glucose+0.5mL ropivacaine at 0.75%). After induction to anesthesia and maintenance with isoflurane, animals were positioned in right lateral recumbency for pulmonary artery catheterization through the left jugular vein. Spinal anesthesia was carried out with injection of 1mL of local anesthetic using a 22G Quincke tip needle in the L5-L6 space along 1 minute. Dogs were maintained under inhalation anesthesia for 60 minutes in ventral recumbency. HR, FR, MAP, CO, mPAP and body temperature progressively increased in all groups, whereas PCWP increased only in GHYPO at all time points. The TPRI showed significantly higher values in GISO at M1, M5 and M10 compared to the other groups, except for M5, during which GISO differed only from GHYPER. The PVRI increased at M5 compared to MB in GISO. Side effects such as unilateral motor deficit, bladder atony, excitation, acute pain and chemosis were observed. The hemodynamic changes were not relevant, although inhalation anesthesia with isoflurane might have influenced the results. The changes observed in the study demonstrate that motor blockade is likely to be obtained with isobaric and hyperbaric ropivacaine, thereby confirming the influence of baricity on the type of nerve fibers on the spinal cord. The isobaric solution results in a mixed blockade (motor and sensory blockade). Hemodynamic changes such as hypotension and bradycardia were not evidenced in this study, although local anesthetics were administered in low volumes and together with isoflurane anesthesia. Regarding complications, post-anesthetic observation is warranted in order to identify and treat possible changes. Spinal anesthesia in the conditions studied did not cause hemodynamic changes in isoflurane-anesthetized dogs and is thus considered safe for routine practice, although a few complications are prone to occur.(AU)

Applicability of ultra-high performance liquid chromatography-quadrupole-time of flight mass spectrometry for cocaine profiling.

For the first time in China, the chemical profiling of cocaine specimens was performed at the National Narcotics Laboratory. An ultra-high performance liquid chromatography-quadrupole-time of flight mass spectrometry (UHPLC-QTOF-MS) method was developed and validated for simultaneous analysis of 14 cocaine alkaloids and 5 main adulterants. Among them, ecgonine methyl ester, ecgonine, benzoylecgonine, and norcocaine were identified by comparing with the standard materials; tropacocaine, 3,4,5-trimethoxycocaine, cis-/trans-cinnamoylcocaine were tentatively identified based on the exact masses of protonated molecules and product ions; six unidentified alkaloids of 182/1.47, 316/9.54, 659/9.85, 316/9.87, 420/10.34, and 420/10.85 were marked with 'extracted mass/retention time' for convenience. Minimum sample preparation and analysis time were required, which was suitable for routine analysis. Based on the semi-quantitative data set of 14 alkaloid impurities in 131 linked/unlinked cocaine samples, 50 combinations of pretreatment methods and distance/correlation measurements were tested for their potential discrimination power for cocaine profiling, and Logarithm/Pearson exhibited the best result. After hierarchical cluster analysis (HCA), 183 cocaine samples collected from 2011 to 2015 were classified into 7 major groups. Moreover, 37 groups of linked samples were found within and between provinces, which provide intelligence for the case connection and revealing of the distribution networks. Our results highlighted the practical utilities of drug profiling, especially to support the investigation through operational intelligence and to improve the knowledge related to the drug trafficking through strategic intelligence. Copyright © 2016 John Wiley & Sons, Ltd.