Due to an increase in diagnosis and prescription of methylphenidate and other ADD/ADHD medications, concerns have been expressed over the rise in Ritalin diversion from prescription to nonmedical use. The objective of this study was to investigate the relationships between the dimensions of self-perception (i.e., Impulse Control, Body Image, Mastery of the External World, Worry Control) self-enhancement, environmental and demographic factors, and non-prescribed Ritalin (methylphenidate) use. This cross sectional study draws on secondary data from the Adolescent Health Risk Behaviors Survey (AHRBS). The secondary data from AHRBS were analyzed using a sample size of n=1992 and a sub-sample size of n=79. Subjects completed questions pertaining to the dimensions of self-perception, self-enhancement, and demographic factors. The results of this study reveal that females who have worse Body Image, and compare their exams to their previous exams are on average more likely to use non-prescribed Ritalin. As a result, researchers in this area may want to focus on self-perception and self-enhancement in order to better understand illicit drug use. Future research should explore the difference between experimentation vs. regular users and how to incorporate this into effective and efficient drug prevention programs.

Objectives: This pilot study examined how Methylphenidate (MPH0.5mg/kg) affects appetite sensations, food reinforcement, energy intake (EI), macronutrient consumption, and weight-loss in youth and adults living with obesity, without ADHD. Methods: This study employed a randomized, double-blind, placebo-controlled design. Eleven participants aged 28±6.9 yrs. (4 M, 7 F) were randomized to receive either MPH (n=5) or placebo group (n=6) for 60 days. Participants’ appetite sensations (Visual Analogue Scale), relative-reinforcing value of food (computer task), EI and macronutrient consumption (ad libitum buffet), and anthropometric measurements (DEXA) were measured at baseline and 60 days. Results: Repeated measures ANOVA revealed group x time interactions for appetite sensations [desire to eat (p=0.01), hunger (p=0.002), and prospective food consumption (p=0.006)]; with greater reductions in MPH group compared to placebo. For the sense of fullness, there was an interaction between group and time (p=0.01), with a greater increase for MPH compared to placebo. Body weight significantly decreased in both groups (p=0.01), with a moderate to large effect size favouring the MPH group (-2.66 kg vs. – 1.16 kg, Cohen’s d =0.76). Changes between MPH and placebo did not differ significantly on EI, macronutrient consumption, or food reinforcement. Conclusions: Our data indicate for the first time that MPH suppresses appetite in individuals with obesity resulting in a moderate–sized effect on weight loss in the short-term. These findings warrant a larger trial to more definitively examine the effect that MPH has on weight loss and maintenance of weight loss, thereby evaluating its potential as a novel pharmacological agent in the management of obesity.

Existem muitos tratamentos para o transtorno de déficit de atenção/hiperatividade (TDAH) em adultos. O metilfenidato é a medicação mais estudada neste transtorno. Embora eficaz, pouco se sabe sobre os fatores associados ao início e ao abandono do metilfenidato em adultos com TDAH. Diversas variáveis sócio-demográficas e clínicas associadas ao início e à permanência em uso de metilfenidato foram avaliadas neste estudo prospectivo de adultos atendidos em um ambulatório especializado em TDAH. Foram diagnosticados 320 pacientes de acordo com os critérios do DSM-IV. O diagnóstico de TDAH foi realizado com a versão para o português do K-SADS, adaptada para adultos. A presença de comorbidades psiquiátricas do eixo I foi avaliada através do SCID-IV. Variáveis categóricas foram analisadas pelo teste do qui-quadrado, seguido de análise dos resíduos. As associações significativas (p ≤ 0,05) foram incluídas conjuntamente em uma regressão logística. Variáveis contínuas foram analisadas através de ANOVA. O abandono pré-tratamento com metilfenidato esteve associado aos diagnósticos de transtorno bipolar e de pânico em remissão e aos diagnósticos atuais de depressão maior, abuso de álcool e transtorno opositor desafiante. A fobia social (atual e em remissão) foi associada ao abandono do tratamento após o início do metilfenidato. Fatores sócio-demográficos e gravidade do TDAH não foram associados aos desfechos estudados. Os achados deste estudo sugerem que as comorbidades desempenham um papel importante no desfecho do tratamento do TDAH em adultos. / There are many treatments available to adult Attention-Deficit Hyperactivity Disorder (ADHD). The most studied medication in this disorder is methylphenidate. Although effective, little is known about factors associated to pretreatment attrition and dropout from methylphenidate in adults with ADHD. The present study evaluates several sociodemographic and clinical variables possibly associated to pretreatment attrition (non-attendance and refusal) and dropout from methylphenidate in a sample of adult ADHD patients in a prospective naturalistic design. Three hundred and twenty subjects were evaluated according DSM-IV criteria. ADHD diagnosis was performed with the Portuguese version of KSADS adapted to adults and the presence of Axis 1 psychiatric comorbidities was evaluated with SCID-IV. Comparisons between categorical variables were performed with the chi-square test followed by residual analysis. All significant associations (p ≤ 0.05) were included in a logistic regression analysis. Continuous variables were analyzed by ANOVA. Non-attendance was more common among patients with lifetime diagnoses of bipolar and panic disorders, and current diagnoses of major depressive episode, alcohol abuse and oppositional defiant disorder. Dropout was associated with current and lifetime social phobia. Sociodemographic factors and ADHD severity were not associated to treatment outcomes. The present findings suggest that psychiatric comorbid disorders have a major role in methylphenidate outcomes in adults with ADHD.

Existem muitos tratamentos para o transtorno de déficit de atenção/hiperatividade (TDAH) em adultos. O metilfenidato é a medicação mais estudada neste transtorno. Embora eficaz, pouco se sabe sobre os fatores associados ao início e ao abandono do metilfenidato em adultos com TDAH. Diversas variáveis sócio-demográficas e clínicas associadas ao início e à permanência em uso de metilfenidato foram avaliadas neste estudo prospectivo de adultos atendidos em um ambulatório especializado em TDAH. Foram diagnosticados 320 pacientes de acordo com os critérios do DSM-IV. O diagnóstico de TDAH foi realizado com a versão para o português do K-SADS, adaptada para adultos. A presença de comorbidades psiquiátricas do eixo I foi avaliada através do SCID-IV. Variáveis categóricas foram analisadas pelo teste do qui-quadrado, seguido de análise dos resíduos. As associações significativas (p ≤ 0,05) foram incluídas conjuntamente em uma regressão logística. Variáveis contínuas foram analisadas através de ANOVA. O abandono pré-tratamento com metilfenidato esteve associado aos diagnósticos de transtorno bipolar e de pânico em remissão e aos diagnósticos atuais de depressão maior, abuso de álcool e transtorno opositor desafiante. A fobia social (atual e em remissão) foi associada ao abandono do tratamento após o início do metilfenidato. Fatores sócio-demográficos e gravidade do TDAH não foram associados aos desfechos estudados. Os achados deste estudo sugerem que as comorbidades desempenham um papel importante no desfecho do tratamento do TDAH em adultos. / There are many treatments available to adult Attention-Deficit Hyperactivity Disorder (ADHD). The most studied medication in this disorder is methylphenidate. Although effective, little is known about factors associated to pretreatment attrition and dropout from methylphenidate in adults with ADHD. The present study evaluates several sociodemographic and clinical variables possibly associated to pretreatment attrition (non-attendance and refusal) and dropout from methylphenidate in a sample of adult ADHD patients in a prospective naturalistic design. Three hundred and twenty subjects were evaluated according DSM-IV criteria. ADHD diagnosis was performed with the Portuguese version of KSADS adapted to adults and the presence of Axis 1 psychiatric comorbidities was evaluated with SCID-IV. Comparisons between categorical variables were performed with the chi-square test followed by residual analysis. All significant associations (p ≤ 0.05) were included in a logistic regression analysis. Continuous variables were analyzed by ANOVA. Non-attendance was more common among patients with lifetime diagnoses of bipolar and panic disorders, and current diagnoses of major depressive episode, alcohol abuse and oppositional defiant disorder. Dropout was associated with current and lifetime social phobia. Sociodemographic factors and ADHD severity were not associated to treatment outcomes. The present findings suggest that psychiatric comorbid disorders have a major role in methylphenidate outcomes in adults with ADHD.

Existem muitos tratamentos para o transtorno de déficit de atenção/hiperatividade (TDAH) em adultos. O metilfenidato é a medicação mais estudada neste transtorno. Embora eficaz, pouco se sabe sobre os fatores associados ao início e ao abandono do metilfenidato em adultos com TDAH. Diversas variáveis sócio-demográficas e clínicas associadas ao início e à permanência em uso de metilfenidato foram avaliadas neste estudo prospectivo de adultos atendidos em um ambulatório especializado em TDAH. Foram diagnosticados 320 pacientes de acordo com os critérios do DSM-IV. O diagnóstico de TDAH foi realizado com a versão para o português do K-SADS, adaptada para adultos. A presença de comorbidades psiquiátricas do eixo I foi avaliada através do SCID-IV. Variáveis categóricas foram analisadas pelo teste do qui-quadrado, seguido de análise dos resíduos. As associações significativas (p ≤ 0,05) foram incluídas conjuntamente em uma regressão logística. Variáveis contínuas foram analisadas através de ANOVA. O abandono pré-tratamento com metilfenidato esteve associado aos diagnósticos de transtorno bipolar e de pânico em remissão e aos diagnósticos atuais de depressão maior, abuso de álcool e transtorno opositor desafiante. A fobia social (atual e em remissão) foi associada ao abandono do tratamento após o início do metilfenidato. Fatores sócio-demográficos e gravidade do TDAH não foram associados aos desfechos estudados. Os achados deste estudo sugerem que as comorbidades desempenham um papel importante no desfecho do tratamento do TDAH em adultos. / There are many treatments available to adult Attention-Deficit Hyperactivity Disorder (ADHD). The most studied medication in this disorder is methylphenidate. Although effective, little is known about factors associated to pretreatment attrition and dropout from methylphenidate in adults with ADHD. The present study evaluates several sociodemographic and clinical variables possibly associated to pretreatment attrition (non-attendance and refusal) and dropout from methylphenidate in a sample of adult ADHD patients in a prospective naturalistic design. Three hundred and twenty subjects were evaluated according DSM-IV criteria. ADHD diagnosis was performed with the Portuguese version of KSADS adapted to adults and the presence of Axis 1 psychiatric comorbidities was evaluated with SCID-IV. Comparisons between categorical variables were performed with the chi-square test followed by residual analysis. All significant associations (p ≤ 0.05) were included in a logistic regression analysis. Continuous variables were analyzed by ANOVA. Non-attendance was more common among patients with lifetime diagnoses of bipolar and panic disorders, and current diagnoses of major depressive episode, alcohol abuse and oppositional defiant disorder. Dropout was associated with current and lifetime social phobia. Sociodemographic factors and ADHD severity were not associated to treatment outcomes. The present findings suggest that psychiatric comorbid disorders have a major role in methylphenidate outcomes in adults with ADHD.

Conselho Nacional de Desenvolvimento CientÃfico e TecnolÃgico / O Transtorno de DÃficit de AtenÃÃo e Hiperatividade (TDAH) à uma desordem do desenvolvimento neurocomportamental que afeta de 3 a 5% das crianÃas em idade escolar. O transtorno à caracterizado pela presenÃa de sintomas como desatenÃÃo, hiperatividade e impulsividade. CrianÃas expostas ao Ãlcool durante o perÃodo gestacional exibem um padrÃo de hiperatividade, dÃficit de linguagem e aprendizado. A Dopamina e a Noradrenalina parecem ter um papel primÃrio na gÃnese do transtorno, o que à confirmado pela resposta ao psicoestimulantes que aumentam suas quantidades na fenda sinÃptica. O psicoestimulante Metilfenidato à a droga de primeira escolha no tratamento do TDAH. MedicaÃÃes nÃo-psicoestimulantes como o inibidor da recaptaÃÃo de noradrenalina Reboxetina, tÃm ganhado forÃa como possÃvel alternativa no tratamento do dÃficit de atenÃÃo. Em ratos, o etanol administrado no perÃodo de neurodesenvolvimento gera disfunÃÃo em circuitos prÃ-frontais, levando a transmissÃo dopaminÃrgica anormal. O objetivo desse trabalho foi avaliar os efeitos comportamentais (memÃria, atenÃÃo, atividade locomotora, depressÃo e ansiedade) do Metilfenidato (MFD) e da Reboxetina (RBX) em modelo de dÃficit de atenÃÃo induzido em camundongos pela lesÃo por etanol. Camundongos Swiss machos e fÃmeas no 10o dia de vida foram submetidos a injeÃÃo de etanol (2 x 2,5g/kg, s.c., 6 h-intervalo) ou soluÃÃo salina (mesmo volume). No 30o dia, iniciaram-se testes comportamentais (T-maze, Y-Maze, esquiva passiva, nado-forcado, plus-maze, caixa claro-escuro e campo-aberto). Os animais receberam MFD (2,5mg/kg) ou RBX (10 mg/kg) por gavagem 30 minutos antes de cada sessÃo de testes.. NÃo se observaram alteraÃÃes histopatolÃgicas em cortes de cÃrtex cerebral dos camundongos lesados por etanol. No T-Maze, o grupo do etanol apresentou significativos (p<0,001, Teste de Kruskal-Wallis) dÃficits de atenÃÃo, necessitando de mais sessÃes para aprender. Os dÃficits foram revertidos pelo MFD e pela RBX. (Cont. 1,5Â0,32, Et 7,18Â0,32, MFD+Et 3,14Â0,88, RBX+Et 1,55Â0,33). Na fase de discriminaÃÃo tardia, os animais lesados tambÃm apresentaram dÃficits de memÃria, com menor nÃmero de acertos quando comparados aos controles. O efeito revertido pelo MFD, mas nÃo pela RBX. (Cont. 25,78Â0,86, Et 21,27Â1,02, MFD+Et 25,14Â1,03, RBX+Et 21,88Â1,00) NÃo houve dÃficits de memÃria aversiva na Esquiva Passiva. No Y-Maze, o grupo do etanol apresentou dÃficits de memÃria de trabalho, revertidos pelo MFD, mas nÃo por RBX. (Cont. 73,28Â4,75, Et 43,53Â4,65, MFD+Et 60,57Â1,92, RBX+Et 54,63Â2,80). No Campo Aberto, o grupo do etanol teve hipoatividade motora, o que foi mitigado por MFD e RBX (Cont. 93,59Â6,38, Et 66,52Â5,87, MFD+Et 98,14Â9,23, RBX+Et 77,3Â7,68) No Claro-Escuro, o grupo do etanol mostrou comportamento ansiogÃnico, permanecendo menos tempo no claro, o que foi revertido pela RBX. (Cont. 149Â5,99, Et 115,4Â4,27, MFD+Et 120,1Â6,81, RBX+Et 149,1Â2,55). No Plus-Maze, o grupo etanol apresentou comportamento ansiogÃnico, revertido pela RBX, mas nÃo pelo MFD (Cont. 88,06Â12,52, Et 50,53Â5,99, MFD+Et 39,86Â12,00, RBX+Et 86,29Â9,49). No Nado-ForÃado, o grupo do etanol teve um comportamento depressivo que nÃo foi melhorado por MFD ou RBX (Cont. 74,17Â23,43, Et 141,8Â19,3, MFD+Et 178,9Â12,43, RBX+Et 118,5Â18,25). ConcluÃmos que camundongos lesados por etanol no perÃodo neonatal apresentam dÃficits de atenÃÃo e memÃria que sÃo adequadamente revertidos por MFD. A RBX permanece como droga de segunda escolha, principalmente em casos onde existem comorbidades como ansiedade. / Attention Deficit and Hyperactivity Disorder (ADHD) is a neurobehavioral disorder that affects between 3 - 5% of scholar-aged children. The disorder is characterized by inattention, hyperactivity and impulsivity. Children exposed to alcohol during pregnancy may exhibit hyperactivity, language and learning deficits. Dopamine and Norepinephrine seem to have an important role in the pathophysiology, which is confirmed by the response to psychostimulants, which increase the availability of these neurotransmitters in the synaptic cleft. The psychostimulant Methylphenidate is the gold-standard in the treatment of ADHD. Non-stimulant medications, such as norepinephrine reuptake inhibitor Reboxetine are gaining space as an alternative in the treatment of ADHD. In rats, when ethanol is given during the period of brain development, it may cause pre-frontal circuitsâ dysfunction and abnormal dopaminergic transmission. The aim of this work is to evaluate the behavioral effects (attention, memory, motor activity, anxiety and depression) of Methylphenidate (MPH) and Reboxetine (RBX) in an experimental model of attention deficit induced by ethanol in mice. Male and female Swiss mice on the post-natal day 10 were injected with ethanol (2 x 2,5g/kg, s.c., 6 h-interval) or saline (same volume). On post-natal day 30, behavioral testing was started (T-maze, Y-maze, passive avoidance, forced swim test, open field, plus maze and dark/light box). The subjects received either MPH (2,5mg/kg) or RBX (10 mg/kg) p.o, 30 minutes before each test session. There were no histopathologic changes in cerebral cortex of mice that received ethanol. In the T-maze, ethanol subjects had significant attention deficits, taking a longer time to learn, but these were reversed by MPH and RBX (Cont. 1,5Â0,32, Et 7,18Â0,32, MPH+Et 3,14Â0,88, RBX+Et 1,55Â0,33). During delayed discrimination, ethanol group had memory deficits, with fewer correct choices than controls. MPH ameliorated the deficits, but RBX did not (Cont. 25,78Â0,86, Et 21,27Â1,02, MPH+Et 25,14Â1,03, RBX+Et 21,88Â1,00). There were no deficits in aversive memory during passive avoidance test. In the Y-Maze, ethanol subjects had working memory deficits, that were mitigated MPH, but not by RBX. (Cont. 73,28Â4,75, Et 43,53Â4,65, MPH+Et 60,57Â1,92, RBX+Et 54,63Â2,80) . At the open field, ethanol subjects had motor hypoactivity that was reversed by MPH and RBX (Cont. 93,59Â6,38, Et 66,52Â5,87, MPH+Et 98,14Â9,23, RBX+Et 77,3Â7,68). At the Light/dark paradigm, ethanol subjects displayed anxious behavior, remaining more time in the dark side and this behavior was reversed by RBX only (Cont. 149Â5,99, Et 115,4Â4,27, MPH+Et 120,1Â6,81, RBX+Et 149,1Â2,55). At the Plus-Maze, ethanol subjects had an anxiogenic behavior, remaining less time in the open arms, and this effect was reversed by RBX (Cont. 88,06Â12,52, Et 50,53Â5,99, MPH+Et 39,86Â12,00, RBX+Et 86,29Â9,49). At the forced swimming test, ethanol subjects had prolonged immobility, which was not reversed by MPH or RBX (Cont. 74,17Â23,43, Et 141,8Â19,3, MPH+Et 178,9Â12,43, RBX+Et 118,5Â18,25). In conclusion, mice exposed to ethanol during brain development have attention and memory deficits that are reversed by MPH and partially by RBX. RBX may be used as a second line treatment in subjects that do not respond to stimulants or have comorbid anxiety.

Attention-deficit/hyperactivity disorder (ADHD) is a well-known and much debated neurological disorder. The core symptoms consist of a lacking ability to maintain focus, hyperactivity and a motoric restlessness. It is a neurological disorder, with its causes under much debate, although this essay identifies some important brain areas and transmitter systems. The aim of this essay is to give an overview of the available treatments for children with ADHD in the form of the two largest groups of treatments; pharmacological treatments and psychosocial treatments. The conclusion found is that pharmacological treatments are more effective at reducing the core symptoms of ADHD, while psychosocial treatments are more effective at improving the development of social functioning, suggesting a combination to be the superior choice.

Attention deficit hyperactivity disorder (ADHD) is a neurobehavioral disorder that affects 11% of children in the US alo­ne. Methylphenidate (MPH) is the most commonly prescribed drug for the treatment of ADHD. Given the fact that ADHD symptoms persist in up to 50% of patients, many children receive MPH from childhood to early adulthood. Unfortunately, most of the scientific literature focuses on the short-term consequences of MPH, even though individuals are taking MPH for many years. MPH acts by blocking dopamine (DA) transporters and norepinephrine transporters, preventing the reuptake of these catecholamines following release. Previous research has shown that long-term exposure to MPH causes dopaminergic neurons within the nigrostriatal pathway to be more sensitive to the Parkinsonian toxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). We hypothesize that oxidative stress caused by the spontaneous oxidation of the excess DA in the synaptic cleft is what’s rendering dopaminergic neurons within the nigrostriatal pathway to be more sensitive to MPTP. Adolescent male Swiss-Webster mice were divided into three cohorts and administered either saline (control), 1 mg/kg MPH (normal dose) or 10 mg/kg (abusive dose) via intraperitoneal (IP) injections for 12 weeks. Mice were injected twice daily, Monday through Friday, mimicking a school-week dosing schedule. After 12 weeks, all animals received a drug washout period of 7 days. Then, half of each cohort was treated with MPTP (4 x 20mg/kg, every 2 hours), while the other half was administered 4 injections of sterile saline. Seven days after MPTP or saline treatment, the mice were sacrificed, brains were removed, and the substantia nigra (SN) and striatum (STR) were collected. Oxidative stress related to increased DA levels was determined using the glutathione assay to measure glutathione (GSH) content and near-infrared fluorescence dot blots to measure free and protein-bound ortho-quinones. GSH is an important antioxidant and thus its depletion would be indicative of oxidative stress. Additionally, since DA may be oxidized to a quinone, increases in free and protein-bound ortho-quinones also indicate oxidative stress. Interestingly, we observed a significant decrease in GSH as the dose of MPH increased with both saline and MPTP samples. Furthermore, there was a significant increase in quinones as the dose of MPH increased. In conclusion, it appears that long-term exposure to MPH sensitizes dopaminergic neurons within the nigrostriatal pathway to oxidative stress, rendering them vulnerable to further insults, such as MPTP exposure. As such, these studies provide insight into the risks of long-term psychostimulant exposure.

Attention deficit hyperactivity disorder (ADHD) is a neurobehavioral disorder that affects 11% of children in the US alo­ne. Methylphenidate (MPH) is the most commonly prescribed drug for the treatment of ADHD. Given the fact that ADHD symptoms persist in up to 50% of patients, many children receive MPH from childhood to early adulthood. Unfortunately, most of the scientific literature focuses on the short-term consequences of MPH, even though individuals are taking MPH for many years. Previous research has shown that long-term exposure to MPH causes dopamine-releasing neurons within the nigrostriatal pathway to die when exposed to the Parkinsonian toxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). MPH acts by blocking dopamine transporters and norepinephrine transporters, preventing the reuptake and removal of these neurotransmitters following release and increasing the time outside of the protective environment of the neuron’s vesicles. We hypothesize that spontaneous oxidation of excess dopamine to a quinone metabolite is rendering these neurons within this particular pathway to be more sensitive to MPTP. The dopamine quinone may be bound by the antioxidant glutathione (GSH) in an effort to protect the cell against oxidative stress. However, as the finite amount of GSH is depleted, the quinone may lead to the production of highly reactive molecules, leading to mitochondrial damage and cell death which may be accelerated by MPTP. In order to examine this hypothesis, we chose to study adolescent male Swiss-Webster mice, which have been shown to be resistant to MPTP’s toxic effects. They were divided into 3 cohorts and administered either saline (control), 1 mg/kg MPH (therapeutic dose) or 10 mg/kg (abusive dose) via intraperitoneal (IP) injections for 12 weeks. Mice were injected twice daily, Monday through Friday, mimicking a school-week dosing schedule. After 12 weeks, all animals received a drug washout period of 7 days. Then, half of each cohort was treated with MPTP (4 x 20 mg/kg, every 2 hours), while the other half was administered 4 injections of sterile saline. Either 3 or 7 days after MPTP or saline treatment, the mice were sacrificed, brains were removed, and the substantia nigra (SN) and striatum (STR) were collected. These areas of the brain make up the nigrostriatal pathway and are affected by Parkinson’s disease. Oxidative stress related to increased dopamine levels was determined using the glutathione assay to measure GSH content, near-infrared fluorescence dot blots to measure free and protein-bound ortho-quinones, and an ATP luciferase assay to measure mitochondrial function. Interestingly, there was a significant decrease in GSH as the dose of MPH was increased with both saline and MPTP samples. Furthermore, a significant increase in quinones was observed as the dose of MPH increased. We also expect to see a decrease in ATP inversely proportional to the dose of MPH indicating increased oxidative stress. In conclusion, it appears that long-term exposure to MPH sensitizes dopaminergic neurons within the nigrostriatal pathway to oxidative stress, rendering them vulnerable to further insults, such as MPTP exposure. As such, these studies provide insight into the risks of long-term psychostimulant exposure.

Commercially available methylphenidate (MPH) exists as a racemic mixture composed of the d- and l-threo enantiomers. Various pharmacokinetic studies of MPH have shown a greater pharmacological potency of the d-threo enantiomer. Furthermore, it was deduced that the stereoselective cleavage of MPH to produce ritalinic acid (RA) by human carboxylesterase results in a higher oral bioavailability of the d-threo enantiomer. As a requirement for pharmaceutical regulation authorities, efforts have been made to determine the differential biological distribution of d- and l-threo MPH and RA enantiomers. In support of these efforts, numerous analytical procedures have been developed for the chiral separation and quantification of MPH enantiomers in a variety of biological matrices. The available methodologies accomplish the enantioseparation and quantification of MPH using gas chromatography, liquid chromatography or capillary electrophoretic techniques coupled with a variety of detectors. The current review discusses the technical procedures involved, and the sensitivity and selectivity of these assays.