Search

This study assessed the relationship between self-esteem, serenity, and anger/impulsivity in a chronic alcohol and other drug (AOD) dependent population. Three hundred participants completed questionnaires addressed to substance abuse, self-esteem, serenity, anger/impulsivity, and other variables. Pearson rs of between 0.55 and 0.61 were found between self-esteem and serenity, anxiety, and anger/impulsivity. Regression analysis indicated that the self-esteem of chronic AOD-dependent individuals was best predicted by serenity, anger/impulsivity, stimulus control, anxiety, and child abuse; serenity and anger/impulsivity each accounted for about 25% of the relative variance. The results suggest that interventions aimed at not only reducing and controlling anger and impulsivity, but increasing feelings of serenity may be helpful in not only increasing self-esteem in this AOD-dependent population, but in fostering increased commitment during the action phase of the treatment program and possibly facilitating relapse prevention. [ABSTRACT FROM AUTHOR]

Procedures for estimating hypnotic depth have been used for more than 70 years. This study predicted self-reported hypnotic depth from the phenomenological and behavioral variables of the Phenomenology of Consciousness Inventory-Hypnotic Assessment Procedure (PCI-HAP). Participants were divided into 2 groups; 1 was used to generate regression equations, and the other group was used for cross-validation. Both imagery vividness during hypnosis (imagoic suggestibility) and the PCI pHGS measure of hypnotic depth (hypnoidal state) accounted for most of the variance in self-reported hypnotic depth. The above results, further supported by correlational and 3-D visual analyses, are consistent with other researchers' observations that ratings of hypnotic depth are a function of: (a) alterations in subjective experience, and (b) the perception of responsiveness to suggestions. The findings are also congruent with J. Holroyd's hypothesis that suggestibility and altered-state effects interact to produce hypnotic effects. [ABSTRACT FROM AUTHOR]

Background: Robot-assisted minimally invasive esophagectomy (RAMIE) is increasingly adopted in centers worldwide, with ongoing refinements to enhance results. This study aims to assess the current state of RAMIE worldwide and to identify potential areas for improvement., Methods: This descriptive study analyzed prospective data from esophageal cancer patients who underwent transthoracic RAMIE in Upper GI International Robotic Association (UGIRA) centers. Main endpoints included textbook outcome rate, surgical techniques, and perioperative outcomes. Analyses were performed separately for intrathoracic (Ivor-Lewis) and cervical anastomosis (McKeown), divided into three time cohorts (2016-2018, 2019-2020, 2021-2023). A sensitivity analysis was conducted with cases after the learning curve (> 70 cases)., Results: Across 28 UGIRA centers, 2012 Ivor-Lewis and 1180 McKeown procedures were performed. Over the time cohorts, textbook outcome rates were 39%, 48%, and 49% for Ivor-Lewis, and 49%, 63%, and 61% for McKeown procedures, respectively. Fully robotic procedures accounted for 66%, 51%, and 60% of Ivor-Lewis procedures, and 53%, 81%, and 66% of McKeown procedures. Lymph node yield showed 27, 30, and 30 nodes in Ivor-Lewis procedures, and 26, 26, and 34 nodes in McKeown procedures. Furthermore, high mediastinal lymphadenectomy was performed in 65%, 43%, and 37%, and 70%, 48%, and 64% of Ivor-Lewis and McKeown procedures, respectively. Anastomotic leakage rates were 22%, 22%, and 16% in Ivor-Lewis cases, and 14%, 12%, and 11% in McKeown cases. Hospital stay was 13, 14, and 13 days for Ivor-Lewis procedures, and 12, 9, and 11 days for McKeown procedures. In Ivor-Lewis and McKeown, respectively, the sensitivity analysis revealed textbook outcome rates of 43%, 54%, and 51%, and 47%, 64%, and 64%; anastomotic leakage rates of 28%, 18%, and 15%, and 13%, 11%, and 10%; and hospital stay of 11, 12, and 12 days, and 10, 9, and 9 days., Conclusions: This study demonstrates favorable outcomes over time in achieving textbook outcome after RAMIE. Areas for improvement include a reduction of anastomotic leakage and shortening of hospital stay., (© 2024. The Author(s).)

Robotic bariatric surgery may overcome challenges associated with laparoscopy, potentially achieving technically superior results. This review aims to summarise current literature reporting on learning curves for surgeons newly adopting robotic bariatrics and implications for safety, efficiency and outcomes. A systematic review was performed in line with the PRISMA guidelines. Electronic databases PubMed and MEDLINE were searched and articles reporting on learning curves in robotic bariatric surgery were identified. Studies that reported changes in outcome over time, or learning curves for surgeons newly adopting robotic bariatric surgery were included in this review. Eleven studies reporting on 1237 patients were included in this review. Most surgeons reported prior bariatric surgical experience. Differences were noted regarding the approach and adoption of robotics. Ten studies found significant reduction in operative time, with the shortest learning curve of 11 cases. Reporting of clinical outcomes was limited. Three studies reported statistically significant improvement in outcomes after the learning curve. Long-term outcomes were in line with current literature, though none assessed differences between learning curve groups. Reported learning curves in robotic bariatric surgery is variable, with limited reporting of clinical outcomes. With appropriate mentorship, surgeons can improve efficiency, safety and clinical outcomes, maximising the benefits of minimally invasive surgery., (© 2024. The Author(s), under exclusive licence to Springer-Verlag London Ltd., part of Springer Nature.)

Cholecystectomy is one of the commonest performed surgeries worldwide. With the introduction of robotic surgery, the numbers of robot-assisted cholecystectomies has risen over the past decade. Despite the proven use of this procedure as a training operation for those surgeons adopting robotics, the consumable cost of routine robotic cholecystectomy can be difficult to justify in the absence of evidence favouring or disputing this approach. Here, we describe a novel method for performing a robot-assisted cholecystectomy using a "three-arm" technique on the newer, 4th generation, da Vinci system. Whilst maintaining the ability to perform precision dissection, this method reduces the consumable cost by 46%. The initial series of 109 procedures proves this procedure to be safe, feasible, trainable and time efficient., (© 2024. Crown.)

Image-guided assessment of bile ducts and associated anatomy during laparoscopic cholecystectomy can be achieved with intra-operative cholangiography (IOC) or laparoscopic ultrasound (LUS). Rates of robotically assisted cholecystectomy (RC) are increasing and herein we describe the technique of intra-corporeal biliary ultrasound during RC using the Da Vinci system. For intraoperative evaluation of the biliary tree during RC, in cases of suspected choledocholithiasis, the L51K Ultrasound Probe (Hitachi, Tokyo, Japan) is used. The extrahepatic biliary tree is scanned along its length, capitalising on the benefits of the full range of motion offered by the articulated robotic instruments and integrated ultrasonic image display using TilePro TM software. Additionally, this technique avoids the additional time and efforts required to undock and re-dock the robot that would otherwise be required for selective IOC or LUS. The average time taken to perform a comprehensive evaluation of the biliary tree, from the hepatic ducts to the ampulla of Vater, is 164.1 s. This assessment is supplemented by Doppler ultrasound, which is used to fully delineate anatomy of the porta hepatis, and accurate measurements of the biliary tree and any ductal stones can be taken, allowing for contemporaneous decision making and management of ductal pathologies. Biliary tract ultrasound has been shown to be equal to IOC in its ability to diagnose choledocholithiasis, but with the additional benefits of being quicker and having higher completion rates. We have described our practice of using biliary ultrasound during robotically assisted cholecystectomy, which is ergonomically superior to LUS, accurate and reproducible., (© 2023. The Author(s), under exclusive licence to Springer-Verlag London Ltd., part of Springer Nature.)

Laparoscopic cholecystectomy has become the standard of care for the treatment of symptomatic gallstone disease. In the context of the increasing uptake of robotic surgery, robotic cholecystectomy has seen a substantial growth over the past decades. Despite this, a formal assessment of the evidence for this practice remains elusive and a randomised controlled trial is yet to be performed. This paper reviews the evidence to date for robotic multiport cholecystectomy compared to conventional multiport cholecystectomy. This systematic review was performed conducted using the Medline, Embase and Cochrane databases; in line with the PRISMA guideline. All articles that compared robotic and conventional laparoscopic cholecystectomy were included. The studies were assessed with regards to operative outcomes, postoperative recovery and complications. Fourteen studies were included, describing a total of 3002 patients. There was no difference in operative blood loss, complication rates, incidence of bile duct injury or length of hospital stay between the robotic and laparoscopic groups. The operative time for robotic cholecystectomy was longer, whereas the risk of conversion to open surgery was lower. There was marked variation in definitions of measured outcomes, and most studies lacked data on training and quality assessment, leading to substantial heterogeneity of the data. Available evidence on multiport robotic cholecystectomy compared to conventional laparoscopic cholecystectomy is scarce and the quality of the available studies is generally poor. Results suggest longer operating time for robotic cholecystectomy, although many studies included the learning curve period. Postoperative recovery and complications were similar in both groups., (© 2023. The Author(s), under exclusive licence to Springer-Verlag London Ltd., part of Springer Nature.)

Background: The adoption of new surgical technologies is inevitably accompanied by a learning curve. With the increasing adoption of robotic techniques in benign foregut surgery, it is imperative to define optimal learning pathways, to ensure a clinically safe introduction of such a technique. The aim of this study was to assess the learning curve for robotic hiatal hernia repair with a pre-defined adoption process and proctoring., Methods: The learning curve was assessed in four surgeons in a high-volume tertiary referral centre, performing over a 100 hiatal hernia repairs annually. The robotic adoption process included simulation-based training and a multi-day wet lab-based course, followed by robotic operations proctored by robotic upper GI experts. CUSUM analysis was performed to assess changes in operating time in sequential cases., Results: Each surgeon (A, B, C and D) performed between 22 and 32 cases, including a total of 109 patients. Overall, 40 cases were identified as 'complex' (36.7%), including 16 revisional cases (16/109, 14.7%). With CUSUM analysis inflection points for operating time were seen after 7 (surgeon B) to 15 cases (surgeon B)., Conclusion: The learning curve for robotic laparoscopic fundoplication may be as little as 7-15 cases in the setting of a clearly organized learning pathway with proctoring. By integrating these organized learning pathways learning curves may be shortened, ensuring patient safety, preventing detrimental outcomes due to longer learning curves, and accelerating adoption and integration of novel surgical techniques., (© 2023. The Author(s).)

Background: Robot-assisted minimally invasive esophagectomy (RAMIE) is gaining increasing popularity as an operative approach. Learning curves to achieve surgical competency in robotic-assisted techniques have shown significant variation in learning curve lengths and outcomes. This study aimed to summarize the current literature on learning curves for RAMIE., Methods: A systematic review was conducted in line with PRISMA guidelines. Electronic databases PubMed, MEDLINE, and Cochrane Library were searched, and articles reporting on learning curves in RAMIE were identified and scrutinized. Studies were eligible if they reported changes in operative outcomes over time, or learning curves, for surgeons newly adopting RAMIE., Results: Fifteen studies reporting on 1767 patients were included. Nine studies reported on surgeons with prior experience of robot-assisted surgery prior to adopting RAMIE, with only four studies outlining a specified RAMIE adoption pathway. Learning curves were most commonly analyzed using cumulative sum control chart (CUSUM) and were typically reported for lymph node yields and operative times, with significant variation in learning curve lengths (18-73 cases and 20-80 cases, respectively). Most studies reported adoption without significant impact on clinical outcomes such as anastomotic leak; significant learning curves were more likely in studies, which did not report a formal learning or adoption pathway., Conclusion: Reported RAMIE adoption phases are variable, with some authors suggesting significant impact to patients. With robust training through formal programmes or proctorship, however, others report RAMIE adoption without impact on clinical outcomes. A formalized adoption curriculum appears critical to prevent adverse effects on operative efficiency and patient care., (© The Author(s) 2022. Published by Oxford University Press on behalf of International Society for Diseases of the Esophagus. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Despite overwhelming evidence of the clinical and financial benefit of urgent cholecystectomy, there is variable enthusiasm and uptake across the UK. In 2014, following the First National Emergency Laparotomy Audit Organisational Report, we implemented a specialist-led urgent surgery service, whereby all patients with gallstone-related pathologies were admitted under the direct care of specialist upper gastrointestinal surgeons. We have analysed 5 years of data to investigate the results of this service model., Methods: Computerised operating theatre records were interrogated to identify all patients within a 5-year period undergoing cholecystectomy. Patient demographics, admission details, length of stay, duration of surgery, and complications were analysed., Results: Between 01/01/2016 and 31/12/2020, a total of 4870 cholecystectomies were performed; 1793 (36.8%) were urgent cases and 3077 (63.2%) were elective cases. All cases were started laparoscopically; 25 (0.5%) were converted to open surgery-14 of 1793 (0.78%) urgent cases and 11 of 3077 (0.36%) elective cases. Urgent cholecystectomy took 20 min longer than elective surgery (median 74 versus 52 min). No relevant difference in conversion rate was observed when urgent cholecystectomy was performed within 2 days, between 2 and 4 days, or greater than 4 days from admission (P = 0.197). Median total hospital stay was 4 days., Conclusion: Urgent laparoscopic cholecystectomy is safe and feasible in most patients with acute gall bladder disease. Surgery under the direct care of upper gastrointestinal specialist surgeons is associated with a low conversion rate, low complication rate, and short hospital stay. Timing of surgery has no effect on conversion rate or complication rate., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Previous studies show that 'poor responders' to Roux-en-Y gastric bypass (RYGBP) may be identified on the basis of early postoperative weight loss. Early identification of poor responders could allow earlier provision of postoperative behavioural and/or intensive lifestyle interventions and enhance their maximal weight loss. Our aim was to investigate whether early postoperative weight loss predicts the maximal weight loss response after RYGBP and sleeve gastrectomy (SG)., Methods: We undertook a retrospective cross-sectional study of 1,456 adults who underwent either RYGBP (n = 918) or SG (n = 538) as a primary procedure in one of two European centres. Postoperative weight loss was expressed as weight loss velocity (WLV) and percentage weight loss. Linear regression analyses were performed to determine the association of early postoperative weight loss with maximal %WL, including adjustment for baseline variables., Results: There was marked variability in maximal %WL following both RYGBP (mean 32.9 %, range 4.1-60.9 %) and SG (mean 26.2 %, range 1.1-58.3 %). WLV 3-6 months postoperatively was more strongly associated with maximal %WL (r (2) = 0.32 for RYGBP and r (2) = 0.26 for SG, P < 0.001 for both) than either WLV 0-6 weeks or 6 weeks to 3 months postoperatively (r (2) = 0.14 and 0.10 for RYGBP, respectively; r (2) = 0.18 and 0.21 for SG, respectively; P < 0.001 for all). Multiple linear regression analysis, including baseline variables of age, sex, preoperative BMI, type 2 diabetes, ethnicity, and bariatric centre, revealed that 3-6 month WLV was an independent predictor of maximal %WL in both SG and RYGBP groups (standardised β-coefficients 0.51 and 0.52, respectively; P < 0.001 for both)., Conclusions: There is a marked variability in weight loss response following RYGBP and SG. Early postoperative weight loss can be used to identify patients whose predicted weight loss trajectories are suboptimal. Early targeting of poor responders with more intensive postoperative lifestyle and behavioural support could potentially enhance their weight loss response.

Background: Roux-en-Y gastric bypass (RYGBP) and sleeve gastrectomy (SG) are the most common bariatric procedures undertaken globally but there are no evidenced-based criteria that inform the selection of one operation over the other. The purpose of this study was thus to compare weight loss outcomes between RYGBP and SG, and to define patient factors affecting weight loss., Methods: A single-centre two-year follow-up retrospective cohort study of all adults who underwent either RYGBP (n = 422) or SG (n = 432) between 2007 and 2012, at University College London Hospitals National Health Service Foundation Trust, an academic tertiary referral centre, was undertaken. Multilevel linear regression was used to compare weight loss between groups, enabling adjustment for preoperative BMI (body mass index) and evaluation for interaction factors., Results: One- and two-year results showed that unadjusted BMI loss was similar between groups; 13.7 kg/m(2) (95% CI: 12.9, 14.6 kg/m(2)) and 12.8 kg/m(2) (95% CI: 11.8, 13.9 kg/m(2)) for RYGBP patients respectively compared with 13.3 kg/m(2) (95% CI: 12.0, 14.6 kg/m(2)) and 11.5 kg/m(2) (95% CI: 10.1, 13.0 kg/m(2)) for SG patients respectively. Adjusting for preoperative BMI, there was 2.2 kg/m(2) (95% CI: 1.5, 2.8) and 2.3 kg/m(2) (95% CI: 1.3, 3.3) greater BMI loss in the RYGBP group compared to the SG group at one and two years respectively (P < 0.001 for both). The interaction analyses demonstrated that age and sex had important differential impacts on SG and RYGBP weight outcomes. Men under 40 and women over 50 years obtained on average far less benefit from SG compared to RYGBP, whereas men over 40 years and women under 50 years experienced similar weight loss with either procedure (P = 0.001 and 0.022 for interaction effects at one and two years respectively)., Conclusions: Our results show that patient sex and age significantly impact on weight loss in a procedure-dependent manner and should be considered when choosing between RYGBP and SG. Optimizing procedure selection could enhance the effectiveness of bariatric surgery, thus further increasing the benefit-to-risk ratio of this highly effective intervention.

In the present study a simple, fast, sensitive and robust method to quantify mirtazapine in human plasma using quetiapine as the internal standard (IS) is described. The analyte and the IS were extracted from human plasma by a simple protein precipitation with methanol and were analyzed by high-performance liquid chromatography coupled to an electrospray tandem triple quadrupole mass spectrometer (HPLC-ESI-MS/MS). Chromatography was performed isocratically on a C(18), 5 µm analytical column and the run time was 1.8 min. The lower limit of quantitation was 0.5 ng/mL and a linear calibration curve over the range 0.5-150 ng/mL was obtained, showing acceptable accuracy and precision. This analytical method was applied in a relative bioavailability study in order to compare a test mirtazapine 30 mg single-dose formulation vs a reference formulation in 31 volunteers of both sexes. The study was conducted in an open randomized two-period crossover design and with a 14 day washout period. Since the 90% confidence interval for C(max) , AUC(last) and AUC(0-inf) were within the 80-125% interval proposed by the Food and Drug Administration and ANVISA (Brazilian Health Surveillance Agency), it was concluded that mirtazapine 30 mg/dose is bioequivalent to the reference formulation, according to both the rate and extent of absorption., (Copyright © 2012 John Wiley & Sons, Ltd.)

In the present study a method to quantify chlorpromazine in human plasma using cyclobenzaprine as the internal standard (IS) is described. The analyte and the IS were extracted from human plasma by a liquid-liquid extraction with diethyl ether/dichloromethane (70/30, v/v) and analyzed by an ultra performance liquid chromatography (UPLC) coupled to an electrospray tandem triple quadrupole mass spectrometer in positive mode (UPLC-ES(+)-MS/MS). Chromatography was performed isocratically on an Aquity UPLC BEH C18 1.7 μm (50 mm × 2.1 mm i.d.) operating at 40°C. The mobile phase was a mixture of 65% water+1% formic acid and 35% of acetonitrile at a flow-rate of 0.5 mL/min. The lowest concentration quantified was 0.5 ng/mL and a linear calibration curve over the range 0.5-200 ng/mL was obtained, showing intra-assay precisions from 2.4 to 5.8%, and inter-assay precisions from 3.6 to 9.9%. The intra-assay accuracies ranged from 96.9 to 102.5%, while the inter-assay accuracies ranged from 94.1 to 100.3%. This analytical method was applied in a relative bioavailability study in order to compare a test chlorpromazine 100 mg simple dose formulation versus a reference in 57 volunteers of both sexes. The study was conducted in an open randomized two-period crossover design and with a fourteen days washout period. Plasma samples were obtained over a 144-h interval. Since the 90% CI for both C(max), AUC(last) and AUC(0-inf) were within the 80-125% interval proposed by the Food and Drug Administration and ANVISA, it was concluded that chlorpromazine 100 mg/dose was bioequivalent to the reference formulation, according to both the rate and extent of absorption., (Copyright © 2011 Elsevier B.V. All rights reserved.)

In the present study a fast, sensitive and robust validated method to quantify chlorpheniramine in human plasma using brompheniramine as internal standard (IS) is described. The analyte and the IS were extracted from plasma by LLE (diethyl ether-dichloromethane, 80:20, v/v) and analyzed by HPLC-ESI-MS/MS. Chromatographic separation was performed using a gradient of methanol from 35 to 90% with 2.5 mm NH(4)OH on a Gemini Phenomenex C(8) 5 microm column (50 x 4.6 mm i.d.) in 5.0 min/run. The method fitted to a linear calibration curve (0.05-10 ng/mL, R > 0.9991). The precision (%CV) and accuracy ranged, respectively: intra-batch from 1.5 to 6.8% and 99.1 to 106.6%, and inter-batch from 2.4 to 9.0%, and 99.9 to 103.1%. The validated bioanalytical procedure was used to assess the comparative bioavailability in healthy volunteers of two dexchlorpheniramine 2.0 mg tablet formulations (test dexchlorpheniramine, Eurofarma, and reference Celestamine, Schering-Plough). The study was conducted using an open, randomized, two-period crossover design with a 2 week washout interval. Since the 90% confidence interval for C(max) and AUC ratios were all within the 80-125% interval proposed by ANVISA and FDA, it was concluded that test and reference formulations are bioequivalent concerning the rate and the extent of absorption., (Copyright (c) 2009 John Wiley & Sons, Ltd.)

The primary goal of the study was to compare adult age groups on aging bias, with measures of knowledge of aging in the physical, psychological, and social domains and life satisfaction. The study sample, consisting of 752 men and women, 40 to 95 years of age, was tested using Neugarten, Havighurst, and Tobin's (1961) Life Satisfaction Index (LSI) and Palmore's Facts on Aging Quiz (1998) modified to extract bias toward older adults and categorized into 3 domains: physical, psychological, and social. Independent variables were 3 levels of LSI from the Neugarten et al. quiz. Aging bias was measured among the age groups, gender, life satisfaction, and knowledge of aging domains. Significant bias differences were found in age group, life satisfaction, and knowledge of aging domain variables. Financial, health, and volunteer status interacted with these effects. Among other significant findings, the data indicate that middle-aged adults 40-59 have the most negative bias in the psychological and social domains and the least negative bias in the physical domain compared to the older participants. Both middle aged and old-old adults have the most negative aging biases. These differential aging stereotypes (positive and negative) among the physical, psychological, and social perceptions of aging over adult age groups are interpreted within aging stereotyping and aging self-stereotyping.

In the present study, a novel, fast, sensitive and robust method to quantify ethinylestradiol in human plasma using 17alpha-ethinylestradiol-d4 as the internal standard (IS) is described. The analyte and the IS were extracted from acidified plasma by liquid-liquid extraction (LLE) using diethyl ether-hexane followed by online solid phase extraction (SPE) using online C18 cartridges. Extracted samples were analyzed by high-performance liquid chromatography coupled to atmospheric pressure photoionization tandem mass spectrometry (HPLC-APPI-MS/MS). Chromatography was performed isocratically on a C18, 5 microm analytical column. The method had a chromatographic run time of 2.50 min and a linear calibration curve over the range 5-500 pg ml(-1) (r(2)>0.9992). The lowest concentration quantified was 5 pg ml(-1), demonstrating acceptable accuracy and precision. The intra-assay precisions ranged from 2.1 to 14.6%, while inter-assay precisions ranged from 4.4 to 11.4%. The intra-assay accuracies ranged from 94.6 to 103.8%, while the inter-assay accuracies ranged from 98.9 to 101.6%. The recovery of ethinylestradiol was determined as part of the assay validation process and was 73.1 and 79.0% for the concentrations 15 and 375 pg ml(-1), respectively. Short-term stability showed that ethinylestradiol was stable in plasma for at least 19 h at room temperature or for at least 385 days when stored at -20 degrees C. In the study of bioequivalence conducted in Brazil, healthy volunteers received two ethinylestradiol 0.035 mg tablet formulations using an open, randomized, two-period crossover design with a 2-week washout interval. Since the 90% confidence interval for C(max) and area under the curve ratios were all inside the 80-125% interval proposed by the US Food and Drug Administration, it was concluded that the two ethinylestradiol formulations are bioequivalent with respect to both the rate and the extent of absorption.

A specific, fast and sensitive high performance liquid chromatography (HPLC) coupled to atmospheric pressure photoionization (APPI) tandem mass spectrometric (LC-MS/MS) assay was developed for the determination of cyproterone (CYP) acetate (CAS 427-51-0) in human plasma. The retention times were 3.26 and 2.90 min for CYP acetate and its internal standard (I. S.) finasteride (FIN), respectively. The overall mean recovery, using liquid/liquid extraction, was found to be 109.0, 107.7 and 100.3%, for low, medium and high concentrations, respectively. Calibration curves were linear in the concentration range of 0.1-50.0 ng/ml, and the lower limit of quantification (LLOQ) was 0.1 ng/ml. The LLOQ, 0.1 ng/ml, was sensitive enough for detecting terminal phase concentrations of the drug. Inter-batch precision of the method ranged from 2.2 to 5.55%, while Inter-batch accuracy ranged from 95.5 to 100.0%. Intra-batch precision ranged from 1.8 to 5.6%, while Intra-batch accuracy ranged from 92.0 to 99.4% at concentrations of 0.3 ng/ml, 20.0 and 40.0 ng/ml. The developed method was applied to a bioequivalenc study of CYP acetate in a group of 44 female volunteers at a single oral dose of a 2 mg tablet, in a combination of ethinylestradiol/CYP acetate (0.25/2 mg). The plasma concentration of CYP acetate did not differ significantly after administration of both formulations (test formulation and the reference one). The geometric mean and respective 90% CI of CYP acetate test/reference percent ratios were 90.66% (84.39-97.40%) for Cmax and 96.20% (90.45-102.33%) for AUC0-t.

An analytical method based on liquid chromatography with positive ion electrospray ionization (ESI) coupled to tandem mass spectrometry detection (LC-MS/MS) was developed for the determination of Verapamil in human plasma using Metoprolol as the internal standard. The analyte and internal standard were extracted from the plasma samples by liquid-liquid extraction and chromatographed on a C(8) analytical column. The mobile phase consisted of methanol-water (70:30; v/v)+12 mM formic acid. The method had a chromatographic total run time of 3.5 min and was linear within the range 1.00-500 ng/mL. Detection was carried out on a Micromass Quattro Ultima tandem mass spectrometer by multiple reaction monitoring (MRM). The intra-run imprecision was less than 5.1% calculated from the quality control (QC) samples, and 16.3% from the limit of quantification (LOQ). The accuracy determined from QC samples were between 92.9 and 103.1%, and 95.2 and 115.3% from LOQ. Concerning the inter-batch analysis, the imprecision was less than 5.8% and 17.3% from QC samples and LOQ, respectively. The accuracy varied between 98.2 and 100.8% from QC and it was 103.1% from LOQ. The protocol herein described was employed in a bioequivalence study of two tablet formulations of Verapamil.

A rapid, sensitive and specific method to quantify carvedilol in human plasma using metoprolol as the internal standard (IS) is described. The analyte and the IS were extracted from plasma by liquid-liquid extraction using a diethyl-ether solvent. After removed and dried the organic phase, the extracts were reconstituted with a fixed volume of acetonitrile-water (50/50; v/v). The extracts were analyzed by a high performance liquid chromatography coupled to electrospray tandem mass spectrometry (HPLC-MS/MS). Chromatography was performed isocratically on Alltech Prevail C18 5 microm analytical column, (150 mm x 4.6 mm i.d.). The method had a chromatographic run time of 3.5 min and a linear calibration curve over the range 0.1-200 ng ml(-1) (r2>0.997992). The limit of quantification was 0.1 ng ml(-1). This HPLC-MS/MS procedure was used to assess the bioequivalence of two carvedilol 25 mg tablet formulations (carvedilol test formulation from Laboratórios Biosintética Ltda and Coreg from Roche Químicos e Farmacêuticos S.A standard reference formulation). A single 25 mg dose of each formulation was administered to healthy volunteers. The study was conducted using an open, randomized, two-period crossover design with a 2-week wash-out interval. Since the 90% CI for C(max) and AUCs ratios were all inside the 80-125% interval proposed by the US Food and Drug Administration Agency, it was concluded that carvedilol formulation elaborated by Laboratórios Biosintética Ltda is bioequivalent to Coreg formulation for both the rate and the extent of absorption.

The laser desorption/ionization (LDI) and matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectra of trinuclear Cs(3)Re(3)Cl(12) and Cs(3)Re(3)Br(12) and dinuclear (Bu(4)N)(2)[Re(2)Cl(8)] are reported. In each case, characteristic fragments due to the loss of halogen atoms give ion signals that can be used to identify the number of rhenium atoms and the identity of ligands bound to the cluster. The ion signals are identified by both m/z values and distinctive isotope patterns. The results presented here illustrate the usefulness of MALDI-TOF mass spectrometry in the characterization of metal atom clusters.