Risk factors and methods in suicides of elderly patients connected to mental health services from 1999-2024.

Introduction: Suicide prevention is an important aspect of psychiatric care, with older men being a population identified at especially high suicide risk and a recent increase in suicides among older women. Methods: Using data collected by the region's quality assurance team, we examined all suicide deaths occurring between March 1999 and February 2024 in patients aged 60 years or older who were connected to the region's Addiction and Mental Health Program at the time of death. Data were analyzed to describe which factors were most commonly identified in suicides in older adults receiving mental healthcare. We also compared male and female cases to determine whether certain factors were more commonly observed in one gender. Results: We identified 48 cases of suicide occurring in patients aged 60 or over. 60% of suicides occurred in males. Overdose and hanging were the most common suicide methods used, and all suicides occurring on inpatient units occurred via hanging. Depression was the most common diagnosis, and was diagnosed more frequently in suicides of female older adults. A greater proportion of suicides in older women were associated with previous history of suicide attempts. Discussion: Our findings support many current best practices for suicide prevention in psychiatric care, including minimizing ligatures and anchor points on inpatient settings, assessing for and limiting access to means in individuals at-risk, and assessing suicide risk in hospitalized patients prior to passes and discharge. Recognition and treatment of depression remain important aspects in the treatment of older adults to prevent suicide.

Sustained remission of psychotic symptoms secondary to hypothyroidism (myxedema psychosis) after 6 months of treatment primarily with levothyroxine: a case report.

BACKGROUND: Psychotic symptoms associated with hypothyroidism, also known as "myxedema psychosis," are a treatable cause of psychosis often associated with complete recovery. While most cases receive both thyroxine and a short course of antipsychotics, some reports indicate that symptoms can resolve without antipsychotic treatment, though follow-up in these cases has often been short or not reported. This is one of the first case reports demonstrating sustained remission of psychotic symptoms at 6 months in a case of myxedema psychosis treated with minimal antipsychotic medication. CASE PRESENTATION: We describe the case of a 40-year-old Caucasian woman who was brought to hospital with a 7-day history of anxiety and decreased sleep and 1 day of disorganized speech, paranoid delusions, and auditory hallucinations. After being admitted to psychiatry for management, screening blood work revealed elevated thyroid-stimulating hormone. The patient was initiated on treatment with levothyroxine and low doses of antipsychotics. Her symptoms resolved on the third day of her admission with ongoing symptomatic remission at 6 months follow-up. CONCLUSIONS: The identification of myxedema psychosis is important owing to the implications on treatment and prognosis of the disorder. Our case suggests that sustained symptom resolution may occur with little to no antipsychotic treatment, though these findings are preliminary and additional study is needed before definitive conclusions on the optimal approach can be made.

Individuals to Systems: Methodological and Conceptual Considerations for Addressing Mental Illness Stigma Holistically.

Mental illness stigma is a complex public health issue that creates barriers for clients needing access to quality mental health services. Most research focuses on interpersonal stigma with emerging research examining intrapersonal and structural stigma in the healthcare setting. This commentary focuses on how to address the gaps in the existing research to elicit greater organizational/structural change in healthcare systems and positive health outcomes. It describes key components of a 5-year multiphase study that aims to explore and address multiple levels of stigma holistically among stakeholders including physicians, nurses, protective services staff, and patients/families in an emergency department setting. Unique to this study is the inclusion of a patient research partner who will be positioned as a co-designer throughout the project. The goal of this study will be to explore, address, understand, and evaluate interventions that mitigate stigma in healthcare at both the individual and structural/organizational levels.

The feasibility and acceptability of mobile application-based assessment of suicidality using self-report components of a novel tool, the Suicide Ideation and Behavior Assessment Tool (SIBAT).

The aim of this study was to assess the validity of a mobile application-based self-report questionnaire in the assessment of suicidality. We developed a program for the administration of self-report components of the Suicide Ideation and Behavior Assessment Tool (SIBAT). We invited university students and trainees enrolled in a study of addictions to complete this component of the SIBAT using the program on their mobile devices or personal computer. 196 participants completed all required modules of the SIBAT, with 97 using their mobile device and 99 using their personal computer. Rates of completed questionnaires between the two groups were compared, as were the responses to the items and the total scores. There was a significant difference between proportions of scale completion in both groups, with a greater number of participants who used a personal computer to complete the scale not responding to all questions compared to participants who used a mobile device to complete the scale. Data collected via mobile device showed good concurrent validity with data collected via personal computer. A trend toward greater disclosure of suicidality was observed in the mobile device group however, replication of these findings using larger sample sizes is needed.

Characterization of the human tear metabolome by LC-MS/MS.

The tear film overlying the epithelial cells of the eye's surface is vital to visual function, and its composition is reflective of ocular surface health. The ultrasmall volume of tears poses challenges in its analysis, contributing to the limited number of reports on the tear metabolome. In addition, using a standard clinical method of tear collection posed some confounding factors in metabonomic analysis. We sought to establish an analytical platform for the global characterization of human tear metabolites. Following information dependent acquisition (IDA) directed liquid chromatography-tandem mass spectrometry (LC-MS/MS), isotope pattern matched peak mining was performed using Extracted Ion Chromatogram (XIC) manager within the PeakView software. Sixty metabolites representing diverse compound classes were identified in human tears, most of which have not been previously reported. Selected metabolites were verified using pure standards. Unsupervised chemometric analysis showed good separation between tear samples and blanks (PC1 = 87%, R(2) = 0.91, Q(2) = 0.87). The results demonstrated the potential of our platform for untargeted metabonomic studies of eye diseases.

Metabolic profiling of 3-nitropropionic acid early-stage Huntington's disease rat model using gas chromatography time-of-flight mass spectrometry.

3-Nitropropionic acid (3-NP), a potent irreversible inhibitor of mitochondrial complex II enzyme, leads to mitochondrial dysfunction and oxidative stress in Huntington's disease (HD) rat model. In this study, biochemical assays were used to demonstrate the presence of oxidative stress and mitochondrial dysfunction in 3-NP early stage HD rat models. Gas chromatography time-of-flight mass spectrometry (GC/TOFMS) was applied to analyze metabolites in brain and plasma of 3-NP-treated and vehicle-dosed rats. The orthogonal partial least-squares discriminant analysis (OPLS-DA) model generated using brain metabolic profiles robustly differentiated the 3-NP early stage HD rat model from the control. Metabonomic characterization of the 3-NP HD rat model facilitated the detection of biomarkers that define the physiopathological phenotype of early stage HD and elucidated the treatment effect of galantamine. Brain marker metabolites that were identified based on the OPLS-DA model were associated with altered glutathione metabolism, oxidative stress, and impaired energy metabolism. The treatment effect of galantamine in early stage HD could not be concluded mechanistically using the brain metabotype. Our study confirmed that GC/TOFMS is a strategic and complementary platform for the metabonomic characterization of 3-NP induced neurotoxicity in the early stage HD rat model.

Extraction of ketamine from urine using a miniature silica monolithic cartridge followed by quantification with liquid chromatography tandem mass spectrometry (LC-MS/MS).

The high surface area monolith with reactive hydroxyl group on its surface enables it to function as a miniature solid-phase extraction (SPE) cartridge in size of 1 cm in diameter and 0.5 cm in length. The prepared silica monolith was characterized by Brunauer-Emmett-Teller method, scanning electron microscopy, X-ray diffraction and Fourier transform infrared (FTIR) spectroscopy. Ketamine was selected as model analyte to validate the extraction efficiency of the prepared cartridge. The extracted ketamine from urine sample was quantitated by liquid chromatography tandem mass spectrometry (LC-MS/MS) using positive electrospray ionization. The limit of detection and quantification for ketamine was found to be 0.5 and 1.6 ng/mL, respectively. The analysis exhibited linearity in the range of 10-500 ng/mL with coefficient of correlation >0.99. The recovery was found to be in the range of 89-107% with relative standard deviation (RSD) less than 10%. The prepared cartridge was found robust in extracting ketamine efficiently and repeatedly without any significant deterioration in its performance. Moreover, the batch-to-batch variations in the performance of the prepared cartridges in terms of % ion suppression of the extracts and recoveries of samples were small, suggesting the consistency in the properties of the monolith.

Mobile App-Based Self-Report Questionnaires for the Assessment and Monitoring of Bipolar Disorder: Systematic Review.

BACKGROUND: Bipolar disorder is a chronic, progressive illness characterized by recurrent episodes of mania and depression. Self-report scales have historically played a significant role in the monitoring of bipolar symptoms. However, these tools rely on episodic memory, which can be unreliable and do not allow the clinician to monitor brief episodic symptoms or the course of symptoms over shorter periods of time. Mobile app-based questionnaires have been suggested as a tool to improve monitoring of patients with bipolar disorder. OBJECTIVE: This paper aims to determine the feasibility and validity of mobile app-based self-report questionnaires. METHODS: We performed a systematic review of the literature according to the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. The PubMed, PsycInfo, Web of Science, Ovid MEDLINE, and EMBASE databases were searched for papers published in English that assessed adherence to and the validity of mobile app-based self-report questionnaires. Relevant studies published from database creation to May 22, 2020, were identified, and results examining the validity of and rates of adherence to app-based self-report questionnaires are reported. RESULTS: A total of 13 records were identified for inclusion in this review. Of these studies, 4 assessed the concurrent validity of mobile app-based self-report tools, with the majority of findings indicating significant associations between data collected using these tools and the Young Mania Rating Scale, Hamilton Depression Rating Scale-17, or Montgomery-Åsberg Depression Rating Scale (P<.001 to P=.24). Three studies comparing the variability or range of symptoms between patients with bipolar disorder and healthy controls suggested that these data are capable of differentiating between known groups. Two studies demonstrated statistically significant associations between data collected via mobile app-based self-report tools and instruments assessing other clinically important factors. Adherence rates varied across the studies examined. However, good adherence rates (>70%) were observed in all but 1 study using a once-daily assessment. There was a wide range of adherence rates observed in studies using twice-daily assessments (42%-95%). CONCLUSIONS: These findings suggest that mobile app-based self-report tools are valid in the assessment of symptoms of mania and depression in euthymic patients with bipolar disorder. Data collected using these tools appear to differ between patients with bipolar disorder and healthy controls and are significantly associated with other clinically important measures. It is unclear at this time whether these tools can be used to detect acute episodes of mania or depression in patients with bipolar disorder. Adherence data indicate that patients with bipolar disorder show good adherence to self-report assessments administered daily for the duration of the study periods evaluated.

Predicting human tissue exposures to xenobiotics using a bottom-up physiologically-based biokinetic model

Advances in physiologically-based biokinetic (PBK) modelling, in vitro-to-in vivo extrapolation (IVIVE) methodologies, and development of permeability-limited biokinetic models have allowed predictions of tissue drug concentrations without utilizing in vivo animal or human data. However, there is a lack of in vivo human tissue concentrations to validate these models. Herein, we validated the performance of our previously published bottom-up rosuvastatin (RSV) PBK model with clinical data from a recently published study that made use of positron emission tomography (PET) imaging to quantify the hepatic concentrations of [11C]RSV drug-drug interaction (DDI) with cyclosporine A (CsA). Simulated RSV area under the plasma concentration-time curve (AUC0h-t) and maximum plasma concentration (Cmax) before and after DDI were within 1.5-fold of the observed data. Simulated AUC0-30min and Cmax ratios in the DDI setting matched the observed ratios closely (within 1.1-fold). To predict RSV hepatic concentrations, the model inputs were modified to account for RSV in the bile canaliculi after biliary excretion. The model recapitulated the observed hepatic concentrations before DDI and the decrease in hepatic concentrations after DDI. Simulated area under the liver concentration-time curve (AUC0-30min,liver), maximum liver concentration (Cmax,liver), AUC0-30min,liver ratio and Cmax,liver ratios were predicted within 1.5-fold of the observed data. In summary, we validated the ability of bottom-up PBK modelling to predict RSV hepatic concentrations with and without DDI with CsA. Our findings confirm the importance to account for drug distributed within the bile canaliculi for accurate prediction of hepatic tissue drug levels when compared against in vivo liver PET scan data.

Internal consistency and concurrent validity of self-report components of a new instrument for the assessment of suicidality, the Suicide Ideation and Behavior Assessment Tool (SIBAT).

This study aimed to assess the internal consistency of self-report components of the Suicide Ideation and Behavior Assessment Tool (SIBAT) and validate it with relevant elements of the Mini International Neuropsychiatric Interview (MINI). The SIBAT is a newly developed instrument for the evaluation of suicidality. In this study, we invited university students and trainees participating in a study of addictions to complete the self-report component of the SIBAT as an add-on study. We evaluated the internal consistency of the self-report component of the SIBAT and validated it against the suicidality component of the MINI. Data were analysed using both complete case analysis and multiple imputation. SIBAT data were collected for 394 participants, 314 of whom had also completed the MINI. The internal consistency of modules 2, 3, and 5 of the SIBAT was high. Each item from module 5 had a statistically significant association with the corresponding item from the MINI. The sum of scores from modules 2 and 3 had a moderate correlation with the assessment of suicide risk determined by the MINI, and a strong correlation with the total score of SIBAT module 5. The completion median time of modules 2, 3 and 5 was 14.3 min.

Metabolic profiling of rat brain and cognitive behavioral tasks: potential complementary strategies in preclinical cognition enhancement research.

In this study, the correlation between the metabolic profiles of rats undergoing cognition enhancement drug therapy and their associated cognitive behavioral outcomes were investigated. Male Lister Hooded rats were administered either with donepezil, galantamine, or vehicle and subjected to Atlantis watermaze training and novel object recognition tests. An UPLC/MS/MS method was developed to profile 21 neurologically related metabolites in the rat brains. Pharmacologically induced behavioral changes were compared subsequently with the metabolic fluctuations of neurologically related metabolites from multiple neurotransmitter pathways using multivariate and univariate statistical analyses. Significant improvements in cognitive behavioral outcomes were demonstrated in the rats administered with donepezil and galantamine using both AWM training (P < 0.05) and NOR (P < 0.05) tests as compared to those dosed with the vehicle. This corroborated with the significant elevation of eight prominent biomarkers after the cognitive enhancement therapy. An orthogonal partial least-squares discriminant analysis model generated using only the 8 metabolites identified as discriminating the drug-dosed rats from the vehicle-dosed rats gave a Q(2) = 0.566, receiver operator characteristic (ROC) AUC = 1.000, using 7-fold cross validation. Our study suggests that metabolic profiling of rat brain is a potential complementary strategy to the cognitive behavioral tasks for characterizing neurobiological responses to cognition enhancement drug testing.

Underlying mitochondrial dysfunction triggers flutamide-induced oxidative liver injury in a mouse model of idiosyncratic drug toxicity.

Flutamide, a widely used nonsteroidal anti-androgen, but not its bioisostere bicalutamide, has been associated with idiosyncratic drug-induced liver injury. Although the susceptibility factors are unknown, mitochondrial injury has emerged as a putative hazard of flutamide. To explore the role of mitochondrial sensitization in flutamide hepatotoxicity, we determined the effects of superimposed drug stress in a murine model of underlying mitochondrial abnormalities. Male wild-type or heterozygous Sod2(+/-) mice were injected intraperitoneously with flutamide (0, 30 or 100 mg/kg/day) for 28 days. A kinetic pilot study revealed that flutamide (100 mg/kg/day) caused approximately 10-fold greater exposure than the reported therapeutic mean plasma levels. Mutant (5/10), but not wild-type, mice in the high-dose group exhibited small foci of hepatocellular necrosis and an increased number of apoptotic hepatocytes. Hepatic GSSG/GSH, protein carbonyl levels, and serum lactate levels were significantly increased, suggesting oxidant stress and mitochondrial dysfunction. Measurement of mitochondrial superoxide in cultured hepatocytes demonstrated that mitochondria were a significant source of flutamide-enhanced oxidant stress. Indeed, mitochondria isolated from flutamide-treated Sod2(+/-) mice exhibited decreased aconitase activity as compared to vehicle controls. A transcriptomics analysis using MitoChips revealed that flutamide-treated Sod2(+/-) mice exhibited a selective decrease in the expression of all complexes I and III subunits encoded by mitochondrial DNA. In contrast, Sod2(+/-) mice receiving bicalutamide (50 mg/kg/day) did not reveal any hepatic changes. These results are compatible with our concept that flutamide targets hepatic mitochondria and exerts oxidant stress that can lead to overt hepatic injury in the presence of an underlying mitochondrial abnormality.

Bottom-up physiologically-based biokinetic modelling as an alternative to animal testing.

There is a growing need for alternatives to animal testing to derive biokinetic data for evaluating both efficacy and safety of chemicals. One such alternative is bottom-up physiologically-based biokinetic (PBK) modeling which requires only in vitro data. The primary objective of this study is to develop and validate bottom-up PBK models of 3 HMG-CoA reductase inhibitors: rosuvastatin, fluvastatin and pitavastatin. Bottom-up PBK models were built using the Simcyp® Simulator by incorporating in vitro transporter and metabolism data (Vmax, Jmax, Km, CLint) obtained from the literature and proteomics-based scaling factors to account for differences in transporters expression between in vitro systems and in vivo organs. Simulations were performed for single intravenous, single oral and multiple oral dose of these chemicals. The results showed that our bottom-up models predicted systemic exposure (AUC0h-t), maximum plasma concentration (Cmax), plasma clearance and time to reach Cmax (Tmax) within two-fold of the observed data, with the exception of parameters associated with multiple oral pitavastatin dosing and single oral fluvastatin dosing. Additional middle-out simulations were performed using animal distribution data to inform tissue-to-plasma equilibrium distribution ratios for rosuvastatin and pitavastatin. This improved the predicted plasma-concentration time profiles but did not significantly alter the predicted biokinetic parameters. Our study demonstrates that quantitative proteomics-based mechanistic in vitro-to-in vivo extrapolation (IVIVE) could account for downregulation of transporters in culture and predict whole organ clearances without empirical scaling. Hence, bottom-up PBK modeling incorporating mechanistic IVIVE could be a viable alternative to animal testing in predicting human biokinetics.

Prevention of acetaminophen (APAP)-induced hepatotoxicity by leflunomide via inhibition of APAP biotransformation to N-acetyl-p-benzoquinone imine.

Acetaminophen (APAP) is safe at therapeutic levels but causes liver injury via N-acetyl-p-benzoquinone imine (NAPQI)-induced oxidative stress when overdose. Recent studies indicated that mitochondrial permeability transition (mPT) plays a key role in APAP-induced toxicity and leflunomide (LEF) protects against the toxicity through inhibition of c-jun NH2-terminal protein kinase (JNK)-mediated pathway of mPT. It is not clearly understood if LEF also exerts its protective effect through inhibition of APAP bioactivation to the toxic NAPQI. The present work was undertaken to study the effect of LEF on the bioactivation of APAP to NAPQI. Mechanism-based inhibition incubations performed in mouse and human liver microsomes (MLM and HLM) indicated that inhibition of APAP bioactivation to NAPQI was observed in MLM but not in HLM. Furthermore, LEF but not its active metabolite, A77-1726, was shown to be the main inhibitor. When APAP and LEF were incubated with human recombinant P450 enzymes, CYP1A2 was found to be the isozyme responsible for the inhibition of APAP bioactivation. Species variation in CYP1A2 enzymes probably accounted for the different observations in our MLM and HLM studies. We concluded that inhibition of NAPQI formation is not a probable pathway that LEF protects APAP-induced hepatotoxicity in human.

Evaluation of BEH C18, BEH HILIC, and HSS T3 (C18) column chemistries for the UPLC-MS-MS analysis of glutathione, glutathione disulfide, and ophthalmic acid in mouse liver and human plasma.

Glutathione (GSH), glutathione disulfide (GSSG), and ophthalmic acid (OA) are important biological oxidative stress biomarkers to be monitored in pathological and toxicological studies. With the advent of liquid chromatography tandem mass spectrometry (LC-MS-MS) technology, sensitive and selective analysis of these biomarkers in biological samples is now being performed routinely. Due to the hydrophilic and polar natures of GSH and its endogenous derivatives, achieving good retention, resolution, and peak shape is often a chromatographic challenge. In this study, three ultra-performance (UP) LC column chemistries (namely, BEH C18, BEH HILIC, and HSS T3 [C18]) are evaluated for the UPLC-MS-MS analysis of GSH, GSSG, and OA extracted from mouse liver and human plasma samples. The chromatographic parameters evaluated are retentivity, tailing factor, MS sensitivity, and resolution of the three analytes. Based on the optimized method for each column chemistry, our results indicate that the HSS T3 (C18) column chemistry affords the best retention and separation of these analytes when operated under the ultra high-pressure chromatographic conditions.

Metabolomic Characterizations of Liver Injury Caused by Acute Arsenic Toxicity in Zebrafish.

Arsenic is one of the most common metalloid contaminants in groundwater and it has both acute and chronic toxicity affecting multiple organs. Details of the mechanism of arsenic toxicity are still lacking and profile studies at metabolic level are very limited. Using gas chromatography coupled with mass spectroscopy (GC/MS), we first generated metabolomic profiles from the livers of arsenic-treated zebrafish and identified 34 significantly altered metabolite peaks as potential markers, including four prominent ones: cholic acid, glycylglycine, glycine and hypotaurine. Combined results from GC/MS, histological examination and pathway analyses suggested a series of alterations, including apoptosis, glycogenolysis, changes in amino acid metabolism and fatty acid composition, accumulation of bile acids and fats, and disturbance in glycolysis related energy metabolism. The alterations in glycolysis partially resemble Warburg effect commonly observed in many cancer cells. However, cellular damages were not reflected in two conventional liver function tests performed, Bilirubin assay and alanine aminotransferase (ALT) assay, probably because the short arsenate exposure was insufficient to induce detectable damage. This study demonstrated that metabolic changes could reflect mild liver impairments induced by arsenic exposure, which underscored their potential in reporting early liver injury.

Metabolic profiling of CHO-AßPP695 cells revealed mitochondrial dysfunction prior to amyloid-ß pathology and potential therapeutic effects of both PPARγ and PPARα Agonisms for Alzheimer's disease.

In this study, we performed gas chromatography time-of-flight mass spectrometry (GC-TOFMS)-based extracellular metabolic profiling on AßPP-transfected CHO cells (CHO-AßPP695) and its wildtype. Orthogonal partial least squares discriminant analysis (OPLS-DA) was then used to identify discriminant metabolites, which gave clues on the effects of AßPP transgene on cellular processes. To confirm the hypotheses generated based on the metabolic data, we performed biochemical assays to gather further evidence to support our findings. The OPLS-DA showed a robust differentiation following 24 h of incubation (Q2(cum) = 0.884) and 15 discriminant metabolites were identified. In contrast, extracellular Aß42 was identified to increase significantly in CHO-AßPP695 only after incubation for 48 h. The observed 24-h metabolic fluxes were associated with increased mitochondrial AßPP and reduced mitochondrial viabilities, which occurred before extracellular Aß accumulation. We also investigated the therapeutic potential of peroxisome proliferator-activated receptor gamma (PPARγ) agonists, namely rosiglitazone (RSG) and pioglitazone (PIO), by employing the same approach to characterize the metabolic profiles of CHO-AßPP695 treated with RSG and PIO, with or without their respective receptor blockers. Treatment with PIO was found to reduce the perturbation of the discriminant metabolites in CHO-AßPP695 to a larger extent than treatment with RSG. We also attributed the PIO effects on the lowering of Aß42, and restoration of mitochondrial activity to PPARγ and PPARα agonism, respectively. Taken together, PIO was demonstrated to be therapeutically superior to RSG. Our findings provide further insights into early disease stages in this AßPP model, and support the advancement of PIO in AD therapy.

An automated LC method for the small-scale purification of organic molecules derived from combinatorial libraries.

This paper presented the development of an automated HPLC small-scale purification method for single bead compounds derived from combinatorial libraries. The method was found to produce higher and more consistent recoveries of purified compounds as compared to conventional manual HPLC purification. Using the manual method, the average percentage recovery of one synthetic compound was determined to be 24% and the coefficients of variation (C.V.%) of recovery were found to be greater than 38%. Using the automated system, the average percentages recovery of a standard compound at 600 and 1000 micromol l(-1) were determined to be 72.63+/-10.17% and 81.34+/-4.39%, respectively. This represented an approximate 3-folds increase in percentage recovery compared to that of the manual small-scale purification process. It was also found that the C.V.% of recovery were less than 15% at both concentration levels. The development of this automated method was found to be straightforward. The importance and implications of this study were discussed.

Applications of monolithic materials for sample preparation.

Recent advances in monolithic columns have made them an alternative to traditional packed columns used in liquid chromatography as well as capillary electrochromatography (CEC). The monolithic columns have been extensively studied and shown to possess several advantages that make them a promising and potential substitute for the particle packed columns. A large number of papers relating to monolithic columns have been published every year, focusing on different preparation techniques, characteristic evaluations as well as applications. This review highlighted the latest development of monoliths for other modes of analytical chemistry. In particular, this review will highlight the application of monoliths for sample preparation which is an important step of the entire analysis.

A sensitive LC/MS/MS bioanalysis assay of orally administered lipoic acid in rat blood and brain tissue.

A sensitive liquid chromatography tandem mass spectrometry (LC/MS/MS) bioanalytical method was developed and validated to analyze lipoic acid (LA) in rat blood and brain samples. Ten mobile phase combinations were investigated during method development. Mobile phase combination of 0.1% acetic acid (pH 4 adjusted with ammonia solution)/acetonitrile was most optimum in terms of sensitivity and peak shape of LA and the internal standard, valproic acid. Sample extraction method was explored using liquid-liquid extraction and protein precipitation methods. Protein precipitation yielded the highest recovery of the analytes from blood and brain ranging from 92 to 115%. The lower limit of quantitation (LLOQ) of LA was 0.1ng/mL (0.485nM) in both blood and brain while on-column lower limit of detection (LLOD) was 0.03pg. The precision (% R.S.D.) ranged from 1.49 to 26.39% and 1.49 to 10.89% for intra- and inter-day assays, respectively. The accuracy ranged from 91.2 to 116.17% for intra-day assay and 102.68 to 114.33% for inter-day assay.