Perception of pharmacy students toward opioid-related disorders and roles of community pharmacists: A French nationwide cross-sectional study.

Background: Community pharmacists are among the frontline health professionals who manage patients with an opioid-related disorder (ORD). Pharmacists frequently have a negative attitude toward these patients, which could have a negative impact on their management. However, education on ORD may improve the attitude of future healthcare professionals. This cross-sectional study aimed to assess French pharmacy students' perceptions of ORD. Methods: This online survey was performed by emails sent to French pharmacy schools (between January 14, 2019 and May 31, 2019). The primary outcome was the perception (visual analogic scale) of ORD as a disease, the roles of community pharmacies (delivery of opioid agonist therapy-OAT and harm reduction kits), and the efficacy of OAT. The secondary outcomes assessed professional experience, university experience of and education on ORD, and the individual characteristics of students. Results: Among the 1,994 students included, 76.3% perceived ORD as a disease and felt that it was normal for pharmacists to deliver OAT (78.9%) and harm reduction kits (74.6%). However, only 46.9% perceived OAT as being effective. Multivariable analyses showed that females had a more positive perception in recognizing ORD as a disease. The progression through university years increased the positive perception of ORD as a disease and the delivery of OAT and harm reduction kits by pharmacists. Education on substance-related disorders had no impact on any scores. Students who had already delivered OAT had a negative perception of their efficacy. The students who had already performed pharmacy jobs or traineeships had a negative perception of harm reduction kit delivery. Conclusion: Education on substance-related disorders had no impact on students' perceptions. It seemed that the maturity acquired through university years had a stronger impact on the students' perceptions of ORD. Efforts must be made to improve our teaching methods and reinforce the confidence of students in the roles of community pharmacists.

A rapid, automatic and accurate assay for quantifying temocillin in human serum and CSF using turbulent flow liquid chromatography coupled to high-resolution mass spectrometry. Clinical application.

Temocillin is a ß-lactamase-resistant penicillin used for the treatment of multiple drug-resistant Gram-negative bacteria. To maximize efficacy and avoid adverse effects, the dose regimen has to be quickly adjusted to the clinical situations. This necessitates the development of a rapid, reliable and accurate analytical method. Temocillin and the stable isotopically labeled internal standard ([13 C6 ]-amoxicillin) were extracted from either serum or cerebrospinal fluid by a turbulent flow liquid chromatographic method and eluted onto an octadecyl-silica phase with polar endcapping. Mass spectrometry was conducted using an exact mass determination method by electrospray positive ionization high-resolution mass spectrometry. The LLOQ and ULOQ of the present method were determined to be 0.4 and 200 µg/ml for serum and cerebrospinal fluid samples, respectively. The total analysis time was <7 min. The recovery ranged from 87.7 to 120.8%. Intra- and inter-day precision and trueness were tested at four concentration levels: 0.4, 8, 40 and 160 µg/ml. Values were 6.33 ± 1.53, 8.8 ± 1.3, 8.8 ± 0.36 and 2.1 ± 0.76%, and 5.0 ± 0.54, 9.9 ± 1.0, 5.8 ± 1.6 and 0.1 ± 1.1%, for inter- and intra-day analysis, respectively. Temocillin was found to be stable under all relevant laboratory conditions. The method was cross-validated with a microbiological assay. This method is suitable for accurate measurement of temocillin concentration in small volumes of serum or cerebrospinal fluid. Thanks to the online extraction procedure, the overall analytical time is compatible with high-throughput analysis for clinical application.

Simultaneous determination of oxacillin and cloxacillin in plasma and CSF using turbulent flow liquid chromatography coupled to high-resolution mass spectrometry: Application in therapeutic drug monitoring.

Cloxacillin and oxacillin are group M penicillins. The therapeutic monitoring of plasma concentrations of these antibiotics and those of their hydroxymethylated metabolites is of great clinical interest, especially in the choice of an adequate dosage allowing an effective treatment while limiting the occurrence of undesirable effects and the development of bacterial resistance. In this context, we conducted this work aiming at developing and validating a method allowing the determination of cloxacillin and oxacillin as well as the identification of their active metabolites in different biological matrices (CSF and plasma) using turbulent flow liquid chromatography coupled to high-resolution mass spectrometry. To do this, we carried out several optimisation tests. Subsequently, we validated our method according to the latest bioanalytical validation recommendations of the European Medicines Agency. The validation results showed that our method is specific and sensitive. We obtained good linearity in the range 0.5 to 100 µg/mL with correlation coefficients above 0.995. The lower limit of quantification was 0.5 µg/mL for each analyte. The method was found to be accurate with repeatability and reproducibility coefficients of variation below 15 %. Our method is also accurate with bias values below 15 %. Recovery values ranged from 87 % to 95 %. Finally, we were able to apply our method to the therapeutic monitoring of the analysed molecules and to identify their active metabolites. Our results suggest that LC-MS shows superiority in the therapeutic monitoring of these antibiotics due to the superiority of specificity shown by this method. This assay method can be routinely used for the daily plasma assays of patients treated with these antibiotics in the context of therapeutic monitoring.

Drug monitoring of a case of citalopram overdosage.

Selective serotonin reuptake inhibitors are widely prescribed drugs without recognized cardiovascular risk. We report the case of a 54-year-old patient who developed QTc interval prolongation, followed by ventricular fibrillation episodes, 10 hours after admission to the ICU, in the setting of a citalopram overdose. Citalopram plasma values dropped from 5.88 to 0.34 mg/L at 9 days postadmission. The patient was treated by oral activated charcoal, and final outcome was favorable.

Detection of LongR3 -IGF-I, Des(1-3)-IGF-I, and R3 -IGF-I using immunopurification and high resolution mass spectrometry for antidoping purposes.

Insulin-like growth factor-I (IGF-I) and its analogs LongR3 -IGF-I, Des(1-3)-IGF-I, and R3 -IGF-I are prohibited substances in sport. Although they were never approved for use in humans, they are readily available as black market products for bodybuilding and can be used to enhance physical performance. This study's aims were to validate a fast and sensitive detection method for IGF-I analogs and to evaluate their detectability after intramuscular administration in rats. The sample preparation consisted of an immunopurification on MSIA™ microcolumns using a polyclonal anti-human-IGF-I antibody. The target substances were then directly analyzed by nano-liquid chromatography coupled with high-resolution mass spectrometry. Abundant signs of lower quality, oxidized peptide forms were found in black market products, justifying the need to monitor at least both the native and mono-oxidized forms. The analytical performance of this method (linearity, carry over, detection limits, precision, specificity, recovery, and matrix effect) was studied by spiking the analogs into human serum. Following a single intramuscular administration (100 µg/kg) in rats, detection was evaluated up to 36 h after injection. While unchanged Des(1-3)-IGF-I and R3 -IGF-I were detected until 24 h after administration, LongR3 -IGF-I disappeared rapidly after 4 h. Des(1)-LongR3 -IGF-I, a new N-terminal Long-R3 -IGF-I degradation product, was detected in addition to Des(1-10)-LongR3 -IGF-I and Des(1-11)-LongR3- IGF-I: the latter was detected up to 16 h. The same products were found after in vitro incubation of the analogs in human whole blood, suggesting that observations in rats may be extrapolated to humans and that the validated method may be applicable to antidoping testing.

A reappraisal of the presence of small or large fiber neuropathy in patients with erythromelalgia.

OBJECTIVE: To assess the contribution of large and small nerve fiber alteration in erythromelalgia (EM). METHODS: Thirty-three EM patients were included and underwent clinical evaluation based on EM severity score, DN4, and Utah Early Neuropathy Scale (UENS) score. Neurophysiological evaluation consisted in nerve conduction studies (NCS) for large nerve fibers and specific tests for small nerve fibers: electrochemical skin conductance, cold and warm detection thresholds, and laser evoked potentials. Finally, the evaluation of vascular changes was based on the presence of clinical feature of microvascular disorders and the measurement of the Toe Pressure Index (TPI). RESULTS: While 28 patients (85%) had vascular alteration on TPI or clinical features, 23 patients (70%) had small-fiber neuropathy on neurophysiological tests, and only 10 patients (30%) had large fiber neuropathy on NCS. Regarding clinical scores, there was no difference between groups (presence or absence of large- or small-fiber neuropathy or microvascular disorder) except for a higher UENS score in patients with large fiber neuropathy. CONCLUSION: Peripheral neuropathy, mostly involving small nerve fibers, is almost as common as microvascular changes in EM, but remains inconstant and not related to a specific neuropathic pattern or higher clinical severity. SIGNIFICANCE: The association of neuropathic and vascular factors is not systematic in EM, this syndrome being characterized by different pathophysiological mechanisms leading to a common clinical phenotype.

Use of capillary dried blood for quantification of intact IGF-I by LC-HRMS for antidoping analysis.

Background: IGF-I is used as a biomarker to detect Growth Hormone doping in athletes' blood samples. Objective: Our aim was to develop and validate a fast, high-throughput and accurate quantification of intact IGF-I from volumetric absorptive microsampling (VAMS) dried blood using LC coupled to high resolution mass spectrometry (LC-HRMS). Methodology & results: IGF-I was extracted from the VAMS, released from its binding proteins, concentrated using microelution SPE and analyzed by LC-HRMS. The method was successfully validated in accordance with the World Anti-Doping Agency's requirements. Subsequently, IGF-I measurements from capillary dried blood and serum were compared. Conclusion: The combination of VAMS, microelution SPE and LC-HRMS is a promising strategy applicable to IGF-I quantification in athletes' samples.

Muscular and mitochondrial effects of long-term fluoxetine treatment in mice, combined with physical endurance exercise on treadmill.

AIM: Fluoxetine, one of the first newer SSRI antidepressant, is an extremely popular treatment for depression that could improve mental health problems. Many recent studies have suggested that SSRI have potential beneficial effects on skeletal muscle tissue. MAIN METHOD: We evaluated the potential beneficial effects of oral fluoxetine (18 mg/kg/day for 6 weeks) on muscle performance, after 6 weeks of physical exercise on treadmill. Male mice were randomly assigned to four groups (n = 12 per group) for treatment. Each group received treatment with following specifications: 1) no exercise with vehicle treatment (SED-S); 2) no exercise with fluoxetine treatment (SED-F); 3) exercise with vehicle treatment (EX-S); and 4) exercise with fluoxetine treatment (EX-F). Exercise performances were assessed based on the exhaustive running time and forelimb grip strength, anxious behavior by elevated plus-maze and open-field tests. Mitochondrial enzymes activity and ROS production were measured in the gastrocnemius and soleus muscles. KEY FINDING: Fluoxetine treatment had a significant effect on maximal aerobic capacity in mice without exercise, but more significant effects on gripping strength and anxiety when combined with exercise training, e.g. increased strength and decreased anxiety. SIGNIFICANCE: Fluoxetine treatment and exercise stimulation also had synergistic effects on strength and increased mitochondrial activity, cellular oxidative and antioxidant capacity in two different muscles.

A new painkiller nanomedicine to bypass the blood-brain barrier and the use of morphine.

The clinical use of endogenous neuropeptides has historically been limited due to pharmacokinetic issues, including plasma stability and blood-brain barrier permeability. In this study, we show that the rapidly metabolized Leu-enkephalin (LENK) neuropeptide may become pharmacologically efficient owing to a simple conjugation with the lipid squalene (SQ). The corresponding LENK-SQ bioconjugates were synthesized using different chemical linkers in order to modulate the LENK release after their formulation into nanoparticles. This new SQ-based nanoformulation prevented rapid plasma degradation of LENK and conferred on the released neuropeptide a notable antihyperalgesic effect that lasted longer than after treatment with morphine in a rat model of inflammation (Hargreaves test). The biodistribution study as well as the use of brain-permeant and -impermeant opioid receptor antagonists indicated that LENK-SQ NPs act through peripherally located opioid receptors. This study represents a novel nanomedicine approach, allowing the specific delivery of LENK neuropeptide into inflamed tissues for pain control.

Comparative antiallodynic activity of morphine, pregabalin and lidocaine in a rat model of neuropathic pain produced by one oxaliplatin injection.

A single infusion of oxaliplatin, a drug active against colorectal cancer, induces specific painful syndrome characterized by neurosensitive symptoms triggered or aggravated in cold conditions. In an animal model that reproduces such hypersensitivity to cold for five days after a single oxaliplatin administration (6mg/kg, i.p.), we assessed the antinociceptive efficacy of intravenously administered drugs such as morphine, lidocaine and pregabalin using the rat tail immersion test in cold water (10 degrees C). The antinociceptive efficacy was first ranked by ratio of the pharmacological effect (versus time) to dose: pregabalin (2mg/kg)>lidocaine (3mg/kg)>morphine (4mg/kg). Our results show that pregabalin may be a good choice to treat cold hypersensitivity after one oxaliplatin injection.

Is pregnancy the time to change alcohol consumption habits in France?

BACKGROUND: Although it is well known that France has a cultural history of alcohol use, no recent French data on alcohol consumption during pregnancy in a large sample are available. METHODS: To determine the alcohol consumption patterns among pregnant women in France, we analyzed data from a 1-year multicenter self-survey. Sociodemographic profile, obstetrical history, neonatal data, and a self-report for assessing drinking patterns during pregnancy including AUDIT were recorded from women who delivered recently. Cases of fetal alcohol syndrome (FAS) were also reported. RESULTS: A total of 837 pregnant women have described all parameters. The mean age at delivery of our sample was 29.7 years (SD = 4.8 years). A total of 52.2% of women indicated that they had consumed alcohol at least once during their pregnancy, and among abstainers 54.5% had a positive AUDIT score. Of the pregnant women who consumed alcohol, 13.7% reported at least one binge drinking episode (5 or more drinks on 1 occasion) during pregnancy. Binge drinking is significantly more frequent than regular alcohol consumption (at least 1 drink more than 1 time per week) during pregnancy. A prevalence rate of FAS of 1.8 per 1,000 live births was observed. CONCLUSIONS: There is a large population of women who still drink alcohol during pregnancy, particularly in binge drinking episodes. This underlines the need to clearly inform women of childbearing age about the dangers of alcohol during pregnancy as related to all types of consumption. Moreover, acting to prevent alcohol consumption prior to pregnancy may also greatly influence prenatal drinking.

Consequences of changes in BDNF levels on serotonin neurotransmission, 5-HT transporter expression and function: studies in adult mice hippocampus.

In vivo intracerebral microdialysis is an important neurochemical technique that has been applied extensively in genetic and pharmacological studies aimed at investigating the relationship between neurotransmitters. Among the main interests of microdialysis application is the infusion of drugs through the microdialysis probe (reverse dialysis) in awake, freely moving animals. As an example of the relevance of intracerebral microdialysis, this review will focus on our recent neurochemical results showing the impact of Brain-Derived Neurotrophic Factor (BDNF) on serotonergic neurotransmission in basal and stimulated conditions. Indeed, although the elevation of 5-HT outflow induced by chronic administration of selective serotonin reuptake inhibitors (SSRIs) causes an increase in BDNF protein levels and expression (mRNA) in the hippocampus of rodents, the reciprocal interaction has not been demonstrated yet. Thus, the neurochemical sight of this question will be addressed here by examining the consequences of either a constitutive decrease or increase in brain BDNF protein levels on hippocampal extracellular levels of 5-HT in conscious mice.

Vincristine-induced neuropathy in the rat is not modified by drug-drug interactions with the P-glycoprotein inhibitor verapamil.

BACKGROUND: Cancer patients can be exposed to drug interactions during treatment with toxic anticancer drugs. The peripheral nervous system is a target for neurotoxic anticancer drugs. P-glycoprotein is essential for the functional integrity of blood-tissue barriers, and P-glycoprotein inhibition due to possible drug interactions could lead to adverse neurotoxic reactions. METHODS: In a rat model of vincristine-induced neuropathy, we assessed the consequences of potential drug interactions of vincristine with some P-glycoprotein-inhibiting drugs, chosen because of their potency to increase the incorporation of (99m)Tc-sestamibi in nervous tissue. RESULTS: Quinidine (30 mg/kg) increased (99m)Tc-sestamibi incorporation in dorsal root ganglia (DRG) but was toxic for rats. Verapamil (30 mg/kg) increased the tracer incorporation in the spinal cord, DRG and sciatic nerve. Combination treatment with the verapamil-vincristine regimen had a tendency to lower weight gain and altered nociceptive thresholds of neuropathic animals. CONCLUSION: Behavioral pain tests did not reveal an increase in vincristine neurotoxicity following combination treatment with verapamil and vincristine. This regimen only led to a slight increase in general toxicity.

Induction of brain Nrf2-HO-1 pathway and antinociception after different physical training paradigms in mice.

AIM: Activation of the Nrf2-antioxidant response element signaling pathway is a major mechanism in the cellular defense against oxidative or electrophilic stress through conjugative reactions and by enhancing cellular antioxidant capacity. Although exercise training up-regulates antioxidant defenses system, while information regarding the intensity levels of physical exercise that acts on the cellular protection systems is limited. MAIN METHODS: The present study evaluated the effects of different durations and intensities of physical exercise on the hippocampus, cortex and hypothalamus Nrf2 and HO-1 gene expression and related protein content and the nociception thresholds in adult C57Bl male mice. Exercise training consisted of daily running on a 10-lane rodent motor-driven treadmill for either 3 or 7 weeks at three different intensities. Pain responses were evaluated after exercise and in untrained mice by Von Frey hair test and cold plate test. KEY FINDINGS: This study confirmed that only vigorous and longer duration aerobic exercise increased Nrf2 protein level in the hippocampus and HO-1 protein level in the cortex and reduced pain perception. Mechanical and thermal hypoalgesia were only observed in exercise groups after 7 weeks of physical training. SIGNIFICANCE: The overall findings in this study confirm that only the long duration intensive forced exercise reduced inflammatory pain by induction of Nrf2/HO-1 antioxidant signaling pathway.

Electrochemical Skin Conductance as a Marker of Painful Oxaliplatin-Induced Peripheral Neuropathy.

PURPOSE: Oxaliplatin is a platinum compound widely used in gastrointestinal cancer treatment but produces dose-limiting peripheral neuropathy. New insights into oxaliplatin-induced peripheral neuropathy (OIPN) assessment are needed to detect more effectively this condition. In this context, we conducted Canaloxa study, a prospective preliminary clinical trial that aimed to investigate how Electrochemical Skin Conductance (ESC), a parameter used in small fiber neuropathy assessment, could be helpful in OIPN diagnosis. METHODS: Cancer patients treated for at least three months with oxaliplatin and suffering from clinically OIPN were included. Electrochemical Skin Conductance, thermal thresholds, and neuropathic pain were assessed in all included patients. RESULTS: During one year, 36 patients were included. The main result was the correlation between ESC and Neuropathic Pain Symptom Inventory score for hands (rho value = -0.69, p < 0.0001) and feet (rho value = -0.79, p < 0.0001). ESC values were lower in neuropathic patients with painful symptoms than in ones without painful symptoms (p = 0.0003 and p < 0.0001 for hands and feet, respectively). No correlation was observed between ESC and thermal thresholds. CONCLUSION: These preliminary data suggest that ESC could be a useful objective marker of painful oxaliplatin-induced neuropathy and could complement the use of subjective clinical scales. This study was prospectively registered on clinicaltrials.gov (NCT02827916) before patient recruitment has begun.

Behavioral and immunohistological assessment of painful neuropathy induced by a single oxaliplatin injection in the rat.

In clinical use, a single infusion of oxaliplatin, widely used to treat metastatic colorectal cancer, induces specific sensory neurotoxicity signs triggered or aggravated by exposure to cold. To study the pathophysiology of these symptoms, we developed and characterized an animal model that reproduces the effects of a single intraperitoneal oxaliplatin administration (3, 6 and 12 mg/kg). Significant allodynia and hyperalgesia to cold stimuli were rapidly observed from 24 h to day 5 with a maximum lowering of 76% at t+30 h versus control. Other behavioral assessments revealed rapid persistent mechanical allodynia, but no thermal hyperalgesia or allodynia to heat and no hyperalgesia to mechanical stimuli. An immunohistochemical study in the superficial layers of the spinal dorsal horn revealed a marked increase in substance P immunoreactivity versus controls (12% versus 4%), whereas calcitonin gene-related peptide (CGRP) immunoreactivity was unchanged. This new animal model for the first time closely mimics the effects observed in humans after a single oxaliplatin infusion, especially onset and highly intense sensory disturbances, hypersensitivity to cold with allodynia and hyperalgesia signs. This model may help to elucidate the mechanisms of this thermal hypersensitivity, especially the possible involvement of small-diameter A-fibers in cold allodynia symptoms. These selective effects may clue up the mechanistic basis for the acute oxaliplatin neuropathy leading to a better understanding of the clinical condition and to optimize its treatment.

Occult maternal exposure to environmental tobacco smoke exposure.

BACKGROUND: Environmental tobacco smoke (ETS) is a recognised air pollutant. Its harmful effects have been found to be implicated in health disorders, including unfavourable pregnancy outcomes. The discrepancy between self-reported environmental tobacco smoke exposure and cotinine levels in pregnant non-smokers in France was examined. METHOD: Plasma cotinine was determined by a CPG-SM method on women who had answered a self-questionnaire describing their habits and environment during pregnancy. RESULTS: Of 698 pregnant women reported as non-smokers, 305 (43.7%) claimed not to be exposed to ETS, yet 196 of these (64.3%) had plasma cotinine levels above the limit of detection. CONCLUSION: Self-reported data on ETS exposure in pregnant women therefore underestimate actual exposure. However, cotinine assay can rectify this misclassification. An accurate identification of this risk factor will help to change attitudes towards ETS and avert its adverse effects on mother and fetus.

Quantification of Chronic Oxaliplatin-Induced Hypesthesia in Two Areas of the Hand.

PURPOSE: Oxaliplatin is a platinum derivate widely used in cancer treatment but producing dose-limiting peripheral neurotoxicity. Acute neuropathy is characterized by a transient cold-induced distal allodynia, whereas chronic neuropathy leads to sensory loss. To design a method for quantitative assessment of oxaliplatin-induced peripheral neuropathy, we developed a study that aims to characterize the most appropriate skin area of the hand to perform sensory tests. METHODS: We included patients treated for at least 6 months with oxaliplatin. Thermal sensory tests are assessed using the Thermotest (Somedic) and consist in measuring thermal thresholds in the thenar and in the fingertips of the opposite hand. Results are analyzed using T-Tests comparing thermal sensory thresholds between the two areas of the hand, globally and then individually. RESULTS: In 7 weeks, 12 patients (7 men and 5 women; mean age: 64.5 years) were included, all treated with FOLFOX protocol. Thermal detection thresholds measured on the fingertips are 146% and 108% greater than the ones measured on the palm for cold and warm, respectively (P < 0.0001). Thermal pain thresholds are difficult to interpret. Regarding individual tests, 9/12 patients and 8/12 patients experienced hypesthesia to cold and warm, respectively. CONCLUSIONS: These results reveal that distal hypesthesia occurring under treatment with oxaliplatin is markedly pronounced in the fingertips; however, as thermal threshold is unknown before treatment, it is difficult to assert that fingertip thermal hypesthesia has developed under treatment. Finally, this short study may be useful to design a method for quantifying oxaliplatin-induced neuropathy.

Involvement of the multidrug resistance transporters in cisplatin-induced neuropathy in rats. Comparison with the chronic constriction injury model and monoarthritic rats.

It has recently been suggested that P-glycoprotein is involved in the genesis and the treatment of the neurotoxic adverse events of anticancer drugs, including vincristine. A lower activity of P-glycoprotein in the peripheral nervous system (PNS) than in the central nervous system could contribute to the neurotoxicity of vincristine. Vincristine treatment is responsible for the induction of multidrug resistance (MDR) gene expression and transporter activity, with deleterious consequences, including a potential decrease in the efficiency of opioid analgesics, antidepressants or antiepileptics. Concerning cisplatin, which is also a strong neurotoxic drug but only an multidrug resistance protein 2 (MRP2) substrate, the same assumption could be suggested for MRP2 nervous function. The aim of this study was to assess MDR gene and protein activity in a rat model of cisplatin-induced neuropathy compared with different peripheral nerve injury models, i.e. mononeuropathy and inflammatory pain (monoarthritis). First, in cisplatin-induced neuropathy, this study demonstrated low MRP2 gene expression in dorsal root ganglia compared with the brain and spinal cord, which could contribute to the strong neurotoxicity of cisplatin in the PNS and particularly the dorsal root ganglia. Thus, gene expression increased in cisplatin-induced neuropathy but decreased in mononeuropathy and remained unchanged in monoarthritis models. Transporter activity of nervous tissues increased in the cisplatin-induced neuropathy, mononeuropathy and monoarthritis to different intensities (3.7-, 1.8- and 1.8-fold, respectively). The development of a MDR in the cisplatin-induced neuropathy is a striking difference with mononeuropathy and monoarthritis models, and characterizes the neuropathies induced by this anticancer drug.

A one-step and sensitive GC-MS assay for meprobamate determination in emergency situations.

A rapid, sensitive, and ready-to-use gas chromatography-mass spectrometry method for meprobamate assay using carisoprodol as internal standard is described. The method involves extracting a 0.2-mL sample with chloroform, previously acidified with HCl 0.2N. For the quantitative analysis, we used selected-ion monitoring mode, selecting the ion m/z 144 for quantification of meprobamate and m/z 245 for carisoprodol. Excellent linearity was found between 0 and 200 mg/L plasma. The limit of detection was 0.58 mg/L, and the limit of quantification was 1.93 mg/L. A high reproducibility [intra-assay coefficient of variation (CV) range of 2.3-4.3% and interassay CV range of 5.5-12.3%] and accuracy (intra-assay range of 96.8-112.3% and interassay range of 85.5-99.3%) were observed. Recoveries were concentration-independent (87.0%, 76.2%, and 81.2% for 20, 75 and 150 mg/L, respectively). No interference from endogenous compounds, other metabolites of meprobamate, or frequently coadministered drugs was detected. This sensitive, simple assay for meprobamate in plasma, whole blood, and urine meets the current requirements for bioanalytical assays in overdose cases.