Using venlafaxine to treat behavioral disorders in patients with autism spectrum disorder.

OBJECTIVE: To test the efficacy of venlafaxine at a dose of 18.75 mg/day on the reduction of behavioral problems such as irritability and hyperactivity/noncompliance in patients with intellectual disabilities and autism spectrum disorder (ASD). Our secondary hypothesis was that the usual doses of zuclopenthixol and/or clonazepam would decrease in the venlafaxine-treated group. METHODS: In a randomized double-blind study, we compared six patients who received venlafaxine along with their usual treatment (zuclopenthixol and/or clonazepam) with seven patients who received placebo plus usual care. Irritability, hyperactivity/noncompliance, and overall clinical improvement were measured after 2 and 8 weeks, using validated clinical scales. RESULTS: Univariate analyses showed that the symptom of irritability improved in the entire sample (p = 0.023 after 2 weeks, p = 0.061 at study endpoint), although no difference was observed between the venlafaxine and placebo groups. No significant decrease in hyperactivity/noncompliance was observed during the study. At the end of the study, global improvement was observed in 33% of participants treated with venlafaxine and in 71% of participants in the placebo group (p = 0.29). The study found that decreased cumulative doses of clonazepam and zuclopenthixol were required for the venlafaxine group. Multivariate analyses (principal component analyses) with at least three combinations of variables showed that the two populations could be clearly separated (p b 0.05). Moreover, in all cases, the venlafaxine population had lower values for the Aberrant Behavior Checklist (ABC), Behavior Problems Inventory (BPI), and levels of urea with respect to the placebo group. In one case, a reduction in the dosage of clonazepam was also suggested. For an additional set of variables (ABC factor 2, BPI frequency of aggressive behaviors, hematic ammonia at Day 28, and zuclopenthixol and clonazepam intake), the separation between the two samples was statistically significant as was the Bartlett's test, but the Kaiser­Meyer­Olkin Measure of Sampling Adequacy was below the accepted threshold. This set of variables showed a reduction in the cumulative intake of both zuclopenthixol and clonazepam. CONCLUSION: Despite the small sample sizes, this study documented a statistically significant effect of venlafaxine. Moreover, we showed that lower doses of zuclopenthixol and clonazepam were needed in the venlafaxine group, although this difference was not statistically significant. This was confirmed by multivariate analyses, where this difference reached statistical significance when using a combination of variables involving zuclopenthixol. Larger-scale studies are recommended to better investigate the effectiveness of venlafaxine treatment in patients with intellectual disabilities and ASD.

Augmented renal clearance, low ß-lactam concentrations and clinical outcomes in the critically ill: an observational prospective cohort study.

Whilst augmented renal clearance (ARC) is associated with reduced ß-lactam plasma concentrations, its impact on clinical outcomes is unclear. This single-centre prospective, observational, cohort study included non-pregnant, critically ill patients aged 18-60 years with presumed severe infection treated with imipenem, meropenem, piperacillin/tazobactam or cefepime and with creatinine clearance (CL(Cr)) ≥60 mL/min. Peak, intermediate and trough levels of ß-lactams were drawn on Days 1-3 and 5. Concentrations were deemed 'subthreshold' if they did not meet EUCAST-defined non-species-related breakpoints. Primary and secondary endpoints were clinical response 28 days after inclusion, and ARC prevalence (CL(Cr)≥130 mL/min) and subthreshold and undetectable concentrations, respectively. Logistic regression was used to evaluate associations between ARC, antibiotic concentrations and clinical failure. From 2010 to 2013, 100 patients were enrolled (mean age, 45 years; median CL(Cr) at inclusion, 144.1 mL/min). ARC was present in 64 (64%) of the patients. Most patients received imipenem/cilastatin (54%). Moreover, 86% and 27% of patients had at least one subthreshold or undetectable trough level, respectively. Among imipenem and piperacillin trough levels, 77% and 61% were subthreshold, respectively, but intermediate levels of both antibiotics were largely above threshold. ARC strongly predicted undetectable trough concentrations (OR=3.3, 95% CI 1.11-9.94). A link between ARC and clinical failure (18/98; 18%) was not observed. ARC and subthreshold ß-lactam antibiotic concentrations were widespread but were not associated with clinical failure. Larger studies are necessary to determine whether standard dosing regimens in the presence of ARC impact negatively on clinical outcome and antibiotic resistance.

Therapeutic drug monitoring of voriconazole: a case report of multiple drug interactions in a patient with an increased CYP2C19 activity.

BACKGROUND: Voriconazole is metabolized by cytochrome P450 (CYP) 2C19 and CYP 3A4. Drug-drug interactions and genetic polymorphisms modulate their activities. CASE PRESENTATION: A 35-year old African female patient with resistant HIV and a cerebral mass of unknown origin was treated with voriconazole for a suspicion of disseminated Aspergillosis infection. Voriconazole trough concentrations (C0) were within target range while the patient was under esomeprazole, a CYP2C19 inhibitor. Phenotyping showed decreased CYP2C19 activity, whereas genotyping showed a variant allele associated with increased enzyme activity. The patient was switched to ranitidine because of the introduction of atazanavir. CYP3A4 inhibition by atazanavir combined with uninhibited CYP2C19 activity resulted in subtherapeutic voriconazole C0. The reintroduction of esomeprazole allowed restoring voriconazole C0 back to target range. CONCLUSION: The integration of drug-drug interactions and pharmacogenetics data is crucial to interpret drug concentrations correctly, thus preventing suboptimal exposure to voriconazole.

Engineering of midbrain organoids containing long-lived dopaminergic neurons.

The possibility to generate dopaminergic (DA) neurons from pluripotent stem cells represents an unlimited source of material for tissue engineering and cell therapy for neurodegenerative disease. We set up a protocol based on the generation of size-calibrated neurospheres for a rapid production (3 weeks) of a high amount of DA neurons (>60%) oriented toward a midbrain-like phenotype, characterized by the expression of FOXA2, LMX1A, tyrosine hydroxylase (TH), NURR1, and EN1. By using γ-secretase inhibitors and varying culture time of neurospheres, we controlled maturation and cellular composition of a three-dimensional (3D) engineered nervous tissue (ENT). ENT contained neurons and glial cells expressing various markers of maturity, such as synaptophysin, neuronal nuclei-specific protein (NeuN), and glial fibrillary acidic protein (GFAP), and were electrophysiologically active. We found that 3-week-old neurospheres were optimal to generate 3D tissue containing DA neurons with typical A9 morphology. ENT generated from 4-week-old neurospheres launched glial cell type since astrocytes and myelin could be detected massively at the expense of TH-immunoreactive neurons. All γ-secretase inhibitors were not equivalent; compound E was more efficient than DAPT in generating DA neurons. This DA tissue provides a tool for drug screening, and toxicology. It should also become a useful biomaterial for studies on Parkinson's disease.

LC-MS (/MS) in clinical toxicology screening methods.

Toxicological screening is the analysis of biological samples to detect and identify unknown compounds. The high selectivity and sensitivity of liquid chromatography (LC) coupled to mass spectrometry (MS) or tandem mass spectrometry (MS/MS) technology provide an attractive alternative to the current methods (LC-UV, GC/MS, etc.). For these reasons, an increasing number of applications are being published. This paper is a brief overview of LC-MS(/MS) screening methods developed for clinical toxicology in recent years. Various sample treatments, chromatographic separations and detection by mass spectrometry can be combined to obtain screening methods adapted to the constraints and needs of clinical toxicology laboratories. Currently the techniques are in the hands of specialists, mainly in academic institutions. However, the evolution in technology should allow application of these techniques as a tool in toxicology laboratories, thus allowing a more widespread exploitation of their potential.

Acute hemorrhagic shock decreases airway resistance in anesthetized rat.

We studied the relation between changes in pulmonary and systemic hemodynamics to those in the airway resistance, respiratory tissue mechanics, and thoracic gas volume (TGV) following acute hemorrhage and blood reinfusion in rats. Forced oscillation technique was used to measure airway resistance (Raw), respiratory tissue damping, and elastance at baseline and after stepwise 1-ml blood withdrawals up to 5 ml total, followed by stepwise reinfusion up to full restoration. Mean systemic (Pam) and pulmonary arterial pressures and suprarenal aortic blood flow were measured at each step. In supplemental animals, plethysmographic TGV, Pam, and respiratory mechanics measurements were performed. Blood volume loss (BVL) led to proportional decreases in Raw (66.5 ± 8.8 vs. 44.8 ± 9.0 cmH(2)O·s·l(-1) with 5 ml, P < 0.001), Pam, and aortic blood flow. In contrast, tissue damping increased significantly (1,070 ± 91 vs. 1,235 ± 105 cmH(2)O/l, P = 0.009 with 5 ml BVL), whereas tissue elastance did not change significantly. TGV significantly increased with acute BVL (3.7 ± 0.2 vs. 4.2 ± 0.2 ml, P = 0.01). Stepwise reinfusions produced opposite changes in the above parameters, with Raw reaching a higher value than baseline (P = 0.001) upon full volume restoration. Both adrenalin (P = 0.015) and noradrenalin levels were elevated (P = 0.010) after 5-ml blood withdrawal. Our data suggest that the decreases in Raw following BVL may be attributed to the following: 1) an increased TGV enhancing airway parenchymal tethering forces; and 2) an increase in circulating catecholamines. The apparent beneficial effect of a reduction in Raw in acute hemorrhagic shock is counteracted by an increase in dead space and the appearance of peripheral mechanical heterogeneities due to de-recruitment of the pulmonary vasculature.

Current role of liquid chromatography coupled to mass spectrometry in clinical toxicology screening methods.

Abstract Toxicological screening is the analysis of a biological specimen to detect and identify compounds in patients admitted to the hospital with acute intoxication of unknown origin. The screening of a wide range of toxicologically relevant compounds in biological samples is a serious challenge for clinical laboratories. The high selectivity and sensitivity of liquid chromatography coupled to mass spectrometry or tandem mass spectrometry technology provides an attractive alternative to the current methods. For these reasons, an increasing number of applications for multi-target screening or general screening of unknown compounds in biological matrices are being published. This paper is an overview of sample clean-up, chromatographic separation and mass spectrometry detection procedures which can be combined to obtain screening methods adapted to the constraints and needs of various laboratories, and none specifically in clinical toxicology. Currently the techniques are in the hands of specialists, principally in academic institutes. However, the evolution in technology should allow application of the techniques as a tool in toxicology laboratories and thus more widespread exploitation of their potential.

Characterization and classification of matrix effects in biological samples analyses.

An exhaustive classification of matrix effects occurring when a sample preparation is performed prior to liquid-chromatography coupled to mass spectrometry (LC-MS) analyses was proposed. A total of eight different situations were identified allowing the recognition of the matrix effect typology via the calculation of four recovery values. A set of 198 compounds was used to evaluate matrix effects after solid phase extraction (SPE) from plasma or urine samples prior to LC-ESI-MS analysis. Matrix effect identification was achieved for all compounds and classified through an organization chart. Only 17% of the tested compounds did not present significant matrix effects.

X-Rank: a robust algorithm for small molecule identification using tandem mass spectrometry.

The diversity of experimental workflows involving LC-MS/MS and the extended range of mass spectrometers tend to produce extremely variable spectra. Variability reduces the accuracy of compound identification produced by commonly available software for a spectral library search. We introduce here a new algorithm that successfully matches MS/MS spectra generated by a range of instruments, acquired under different conditions. Our algorithm called X-Rank first sorts peak intensities of a spectrum and second establishes a correlation between two sorted spectra. X-Rank then computes the probability that a rank from an experimental spectrum matches a rank from a reference library spectrum. In a training step, characteristic parameter values are generated for a given data set. We compared the efficiency of the X-Rank algorithm with the dot-product algorithm implemented by MS Search from the National Institute of Standards and Technology (NIST) on two test sets produced with different instruments. Overall the X-Rank algorithm accurately discriminates correct from wrong matches and detects more correct substances than the MS Search. Furthermore, X-Rank could correctly identify and top rank eight chemical compounds in a commercially available test mix. This confirms the ability of the algorithm to perform both a straight single-platform identification and a cross-platform library search in comparison to other tools. It also opens the possibility for efficient general unknown screening (GUS) against large compound libraries.

Extraction of amino acids by reverse iontophoresis in vivo.

Reverse iontophoresis across the skin is a potentially useful alternative for non-invasive clinical and therapeutic drug monitoring. In this work, the reverse iontophoretic extraction of 17 amino acids was studied in vivo in healthy volunteers. Charged amino acids were primarily extracted towards the electrode of opposite polarity, while zwitterionic species were extracted, more or less equally, to both anode and cathode, suggesting that the net charge on the skin, under the conditions of the experiment, was close to zero. The significant presence of a 'skin reservoir' of several amino acids, presumably originating from the barrier's so-called 'natural moisturizing factor', was deduced from the results. While this phenomenon had been observed in an earlier in vitro investigation, the levels of certain amino acids (including serine and glycine) in the skin were found to be much higher in vivo. Hence, while the results of this study confirm the feasibility of extracting some amino acids at physiologically relevant levels in vivo, the objective of achieving a correlation between iontophoretically extracted fluxes and blood plasma levels may not be a practically realisable goal in all cases.

Extraction of amino acids by reverse iontophoresis: simulation of therapeutic monitoring in vitro.

Reverse iontophoresis across the skin has been investigated as alternative, non-invasive method for clinical and therapeutic drug monitoring. This research investigated the reverse iontophoretic extraction of 19 amino acids present at clinically relevant levels in the subdermal compartment of an in vitro diffusion cell. Over a simulated, systemic concentration range of 0-500 microM, the extraction of amino acids was linear. Charged amino acids were extracted towards the electrode of opposite polarity, while zwitterionic species were extracted to both anode and cathode with the latter predominating. The reverse iontophoretic extraction flux was a linear function of amino acid isoelectric point, reflecting the different contributions of electromigration and electroosmosis to electrotransport. Overall, the results confirm the feasibility of monitoring amino acids at clinically relevant levels and provide an incentive for in vivo research to further explore the clinical potential of reverse iontophoresis for the non-invasive monitoring of amino acids.

Quantification of cyclosporine and tacrolimus in whole blood. Comparison of liquid chromatography-electrospray mass spectrometry with the enzyme multiplied immunoassay technique.

OBJECTIVES: The aim of this work was to compare a validated liquid chromatography-mass spectrometry (LC-MS) method with the commercial enzyme multiplied immunoassay technique (EMIT) for cyclosporine and tacrolimus whole blood quantification. DESIGN AND METHODS: Samples of transplant patients receiving cyclosporine (n=38) or tacrolimus (n=41) were analyzed successively by LC-MS and EMIT. Several statistical approaches for method comparison were evaluated and Passing-Bablok and Bland-Altman analyses chosen. RESULTS: Overestimations of the concentrations measured with EMIT compared to LC-MS were observed with means of 23% (range: 6% to 46%) for cyclosporine and 30% (range: -3% to 73%) for tacrolimus. CONCLUSION: The EMIT demonstrated significant positive biases due to cross-reactions with metabolites. This indicates that, in some clinical situations, a selective method such as LC-MS is preferable for therapeutic drug monitoring in transplant patients.

Simultaneous quantification of cyclosporine, tacrolimus, sirolimus and everolimus in whole blood by liquid chromatography-electrospray mass spectrometry.

OBJECTIVES: The aim of this work was to develop a selective method for the simultaneous quantification of cyclosporine, tacrolimus, sirolimus and everolimus in whole blood. DESIGN AND METHODS: An automated on-line solid-phase extraction system coupled with liquid chromatography-mass spectrometry (LC-MS) was used. After a simple protein precipitation, the supernatant was load on a C8 column with a mobile phase composed of MeOH/H(2)O (5/95 v/v), supplemented with formic acid 0.02% and sodium formate 1 muM. After column-switching, the analytes were transferred in the back-flush mode on a C18 column with MeOH/H(2)O (65/35). The valve was then commuted to its initial position and the chromatographic separation was performed with a gradient of MeOH/H(2)O (65/35-95/5). The sodium adducts [M+Na](+) were monitored for quantification with an electrospray ionization-single quadrupole MS. RESULTS: The LC-MS assay was fully validated on a concentration range of 2.5-30 ng/mL for tacrolimus, sirolimus and everolimus and of 50-1500 ng/mL for cyclosporine, allowing a quantification of cyclosporine 2 h post-dose without sample dilution. Trueness, repeatability and intermediate precision were found to be satisfactory. CONCLUSION: This method provided a selective, rapid and automated procedure that can be easily used for routine quantification of immunosuppressive drugs in most clinical laboratories.

Influence of ABCB1 genetic polymorphisms on cyclosporine intracellular concentration in transplant recipients.

OBJECTIVE: The expression on lymphocytes of P-glycoprotein, an efflux transporter encoded by the ABCB1 gene, might influence cyclosporine intracellular concentration. METHODS: ABCB1 genotypes, cyclosporine intracellular and blood concentrations were determined in 64 stable renal, liver or lung transplant recipients. RESULTS: Cyclosporine intracellular concentration correlated moderately with blood concentration (r=0.30, P<0.00005). The ABCB1 1199A carriers presented a 1.8-fold decreased cyclosporine intracellular concentration (P=0.04), whereas the 3435T carriers presented a 1.7-fold increase (P=0.02) as well as a 1.2-fold increased blood concentration (P=0.04). In contrast, ABCB1 61A>G, 1236C>T and 2677G>T polymorphisms did not influence cyclosporine intracellular and blood concentrations. CONCLUSION: This is the first report demonstrating that ABCB1 polymorphisms influence cyclosporine intracellular concentration. Interestingly, its influence on intracellular concentration is significantly higher than on blood concentration (P<0.002). This may therefore modulate cyclosporine immunosuppressive activity.

Influence of ABCB1 gene polymorphisms and P-glycoprotein activity on cyclosporine pharmacokinetics in peripheral blood mononuclear cells in healthy volunteers.

The calcineurin inhibitor cyclosporine is removed from lymphocytes by the drug efflux transporter P-glycoprotein (P-gp) encoded by the ABCB1 gene for which several single nucleotide polymorphisms (SNPs) have been identified. Of a total of 87 healthy volunteers genotyped for ABCB1 G2677T/A and C3435T SNPs, 10 GG-CC and 9 TT-TT individuals were selected and received a single oral dose of cyclosporine. Peripheral blood mononuclear cell (PBMC) ABCB1 mRNA expression, P-gp activity in CD4(+) and CD8(+) cells and the 24h cyclosporine pharmacokinetics in PBMCs and whole blood were determined. No correlation was observed between cyclosporine PBMC and whole blood levels (AUC(0-24), Spearman, r(S)=0.09, p=0.71). Intraindividual PBMC and whole blood levels followed parallel profiles that did not significantly differ with respect to t(max) (Wilcoxon, p=0.53) and t((1/2)) (p=0.49). Significant negative correlations between cyclosporine t((1/2)) in PBMCs and P-gp activity in CD4(+) (r(S)=-0.82, p=0.007) and CD8(+) (r(S)=-0.72, p=0.03) were observed among TT-TT subjects. Similarly, a negative correlation was detected in the GG-CC group between P-gp activity in CD4(+) and cyclosporine PBMC AUC(0-24) (r(S)=-0.69, p=0.03), as well as PBMC to whole blood AUC(0-24) ratio (r(S)=-0.60, p=0.07). Tested ABCB1 genotypes had no influence on cyclosporine pharmacokinetic parameters in PBMCs and whole blood. The haplotypes investigated were neither significantly correlated with PBMC ABCB1 mRNA expression nor with P-gp activity in CD4(+) and CD8(+). In conclusion, cyclosporine PBMC pharmacokinetics was influenced by P-gp activity and cyclosporine whole blood concentrations did not predict PBMC drug levels, suggesting that despite values in the therapeutic range, some subjects could have inadequate intracellular drug levels.

Hemodynamic effect of angiotensin II receptor blockade in postmenopausal women on a high-sodium diet: A double-blind, randomized, placebo-controlled study.

BACKGROUND: Hypertension becomes increasingly prevalent after menopause. Postmenopausal women are more responsive to salt than premenopausal women, and they have been reported to develop marked renal vasoconstriction on a high-sodium diet. OBJECTIVE: The aim of this study was to assess whether angiotensin II receptor blockade can restore a normal pattern of renal response to salt in postmenopausal women on a high-sodium diet. We also assessed segmental renal sodium handling in that population. METHODS: Normotensive and hypertensive postmenopausal women not receiving hormone replacement therapy were enrolled in this prospective, double-blind, placebo-controlled, crossover study. They were assigned to receive irbesartan 150 mg or placebo for 6 weeks; the sequence in which they received irbesartan or placebo was randomized. During the last week of treatment, they received a high-sodium diet (250 mmol/d). Ambulatory blood pressure (ABP), glomerular filtration rate (GFR), and effective renal plasma flow (ERPF) were measured using sinistrin and para-amino-hippurate clearances. Renal sodium handling was assessed by measuring endogenous lithium clearance on day 7 of the high-salt diet. RESULTS: Nineteen women (mean age, 54.7 years; range, 43-72 years; 7 normotensive subjects [mean age, 53.4 years; range, 47-61 years] and 12 hypertensive subjects [mean age, 55.4 years; range, 43-72 years]) were included in the study. When the data for all 19 subjects were pooled, ABP was significantly lower with irbesartan than placebo both during the day (120 [3]/79 [2] vs 127 [3]/85 [2] mm Hg; both, P < 0.01) and at night (systolic BP, 107 [4] vs 111 [4] mm Hg [P < 0.01] and diastolic BP, 71 [2] vs 75 [2] mm Hg [P < 0.05]). Compared with placebo, irbesartan was not associated with a significant change in GFR in either the normotensive or the hypertensive women. When the data for all 19 subjects were pooled, irbesartan was associated with a significant increase in ERPF compared with placebo (372 [21] vs324 [18] mL/min · 1.73 m(2); P < 0.05). When the hypertensive and normotensive women were considered separately, the effect was more pronounced in the hypertensive women than in the normotensive women, but the changes did not reach statistical significance. When the data for all subjects were pooled, irbesartan was associated with a significant increase in daytime urinary sodium excretion compared with placebo (135 [13] vs 106 [13] µmol/min; P < 0.05) and a significant decrease at night (109 [13] vs 136 [19] µmol/min; P < 0.05). Fractional excretion of lithium (FELi), an inverse marker of proximal sodium reabsorption, increased significantly during the daytime with irbesartan compared with placebo (47% [6.5%] vs 35% [4.7%]; P < 0.05). At nighttime, FELi was significantly higher in the hypertensive subjects receiving irbesartan compared with placebo (43% [7.2%] vs 29% [6.5%]; P < 0.05). The fractional distal reabsorption of sodium did not change significantly with irbesartan compared with placebo. CONCLUSIONS: The results from this study suggest that angiotensin II receptor blockade had a favorable impact on BP, renal hemodynamics, and renal sodium handling in these salt-replete postmenopausal women. Blockade of the renin-angiotensin system restored the normal pattern of renal response to high sodium intake in these women.

Quantification of cyclosporine A in peripheral blood mononuclear cells by liquid chromatography-electrospray mass spectrometry using a column-switching approach.

As a potential alternative to cyclosporine A (CsA) monitoring in whole blood, a sensitive and selective method was developed for quantifying this immunosuppressive drug in human peripheral blood mononuclear cells (PBMCs) by liquid chromatography-electrospray ionization mass spectrometry (LC-ESI-MS). PBMCs were isolated from whole blood by density gradient centrifugation. After purification, cell counts were performed to express CsA amounts per single cell. The pelleted cells were then lysed and CsA was extracted with methanol (MeOH) containing 27-demethoxy-sirolimus as internal standard. After evaporation of the supernatant under nitrogen, the residue was reconstituted in MeOH, further diluted with water and injected onto a column-switching unit. On-line solid-phase extraction was performed using a C8 column with an acidic aqueous mobile phase containing 5% MeOH. The analytes were transferred in the back-flush mode on a C18 column with 65% MeOH and the chromatographic separation performed with a MeOH gradient (65-90%). The detection was carried out with a single quadrupole analyzer and the sodium adducts [M+Na](+) were monitored for quantification. This sensitive method was fully validated in the range of 5-400 ng/mL. This allowed the measurement of very small CsA amounts present in cells up to 0.5 fg/PBMC in clinical samples. Trueness (95.0-113.2%), repeatability (5.1-9.9%) and intermediate precision (7.0-14.7%) were found to be satisfactory. This method represents a new potential tool for therapeutic drug monitoring of CsA and could be used in clinical conditions if the utility of intracellular measurements is confirmed in prospective clinical trials.

Desorption electrospray ionization mass spectrometry: direct toxicological screening and analysis of illicit Ecstasy tablets.

Desorption electrospray ionization mass spectrometry (DESI-MS) was used as a simple and rapid way to analyze drug tablets and powders without sample preparation. Experiments were performed with a home-made DESI source coupled to a triple-quadrupole linear-ion trap (QqQ(LIT)) mass spectrometer. Twenty-one commercial drugs as well as some illicit Ecstasy tablets and powders were analyzed. MS spectra almost exclusively showed the protonated or deprotonated ion of the drug after directing the pneumatically assisted electrospray onto the tablet's surface. With some tablets, inhomogeneity of the surface resulted in different spectra depending on the spot analyzed, thus showing that DESI could be used for imaging. Directly triggered MS/MS spectra were used for confirmatory analysis, with analysis times often below 10 s per tablet. For illicit Ecstasy tablets, DESI-MS, GC/MS and LC/MS analyses provided similar qualitative results for the main analytes. With MS/MS spectra library comparison or exact mass measurements, this technique could become very powerful for the rapid analysis of unknown tablets and shows the great potential of desorption techniques as an alternative to solution-based analysis.