A hybrid method for sag source location in power network

The work presented in this paper belongs to the power quality knowledge area and deals with the voltage sags in power transmission and distribution systems. Propagating throughout the power network, voltage sags can cause plenty of problems for domestic and industrial loads that can financially cost a lot. To impose penalties to responsible party and to improve monitoring and mitigation strategies, sags must be located in the power network. With such a worthwhile objective, this paper comes up with a new method for associating a sag waveform with its origin in transmission and distribution networks. It solves this problem through developing hybrid methods which hire multiway principal component analysis (MPCA) as a dimension reduction tool. MPCA reexpresses sag waveforms in a new subspace just in a few scores. We train some well-known classifiers with these scores and exploit them for classification of future sags. The capabilities of the proposed method for dimension reduction and classification are examined using the real data gathered from three substations in Catalonia, Spain. The obtained classification rates certify the goodness and powerfulness of the developed hybrid methods as brand-new tools for sag classification

Response-to-comments about: "Is it really the method for carbon dioxide determination in human postmortem cardiac gas samples using Headspace-Gas Chromatography-Mass Spectrometry valid?" from T. Saffaj and B. Ihssane

Saffaj et al. recently criticized our method of monitoring carbon dioxide in human postmortem cardiac gas samples using Headspace-Gas Chromatography-Mass Spectrometry. According to the authors, their demonstration, based on the latest SFSTP guidelines (established after 2007 [1,2]) fitted for the validation of drug monitoring bioanalytical methods, has put in evidence potential errors. However, our validation approach was built using SFSTP guidelines established before 2007 [3-6]. We justify the use of these guidelines because of the post-mortem context of the study (and not clinical) and the gaseous state of the sample (and not solid or liquid). Using these guidelines, our validation remains correct.

Ambulatory monitoring of physical activities in patients with Parkinson's disease.

A new ambulatory method of monitoring physical activities in Parkinson's disease (PD) patients is proposed based on a portable data-logger with three body-fixed inertial sensors. A group of ten PD patients treated with subthalamic nucleus deep brain stimulation (STN-DBS) and ten normal control subjects followed a protocol of typical daily activities and the whole period of the measurement was recorded by video. Walking periods were recognized using two sensors on shanks and lying periods were detected using a sensor on trunk. By calculating kinematics features of the trunk movements during the transitions between sitting and standing postures and using a statistical classifier, sit-to-stand (SiSt) and stand-to-sit (StSi) transitions were detected and separated from other body movements. Finally, a fuzzy classifier used this information to detect periods of sitting and standing. The proposed method showed a high sensitivity and specificity for the detection of basic body postures allocations: sitting, standing, lying, and walking periods, both in PD patients and healthy subjects. We found significant differences in parameters related to SiSt and StSi transitions between PD patients and controls and also between PD patients with and without STN-DBS turned on. We concluded that our method provides a simple, accurate, and effective means to objectively quantify physical activities in both normal and PD patients and may prove useful to assess the level of motor functions in the latter.

Tools in pharmacovigilance in psychiatry: therapeutic drug monitoring, pharmacogenetic tests and drug-drug interactions databases

SUMMARYIn order to increase drug safety we must better understand how medication interacts with the body of our patients and this knowledge should be made easily available for the clinicians prescribing the medication. This thesis contributes to how the knowledge of some drug properties can increase and how to make information readily accessible for the medical professionals. Furthermore it investigates the use of Therapeutic drug monitoring, drug interaction databases and pharmacogenetic tests in pharmacovigilance.Two pharmacogenetic studies in the naturalistic setting of psychiatric in-patients clinics have been performed; one with the antidepressant mirtazapine, the other with the antipsychotic clozapine. Forty-five depressed patients have been treated with mirtazapine and were followed for 8 weeks. The therapeutic effect was as seen in other previous studies. Enantioselective analyses could confirm an influence of age, gender and smoking in the pharmacokinetics of mirtazapine; it showed a significant influence of the CYP2D6 genotype on the antidepressant effective S-enantiomer, and for the first time an influence of the CYP2B6 genotype on the plasma concentrations of the 8-OH metabolite was found. The CYP2B6*/*6 genotype was associated to better treatment response. A detailed hypothesis of the metabolic pathways of mirtazapine is proposed. In the second pharmacogenetic study, analyses of 75 schizophrenic patients treated with clozapine showed the influence of CYP450 and ABCB1 genotypes on its pharmacokinetics. For the first time we could demonstrate an in vivo effect of the CYP2C19 genotype and an influence of P-glycoprotein on the plasma concentrations of clozapine. Further we confirmed in vivo the prominent role of CYP1A2 in the metabolism of clozapine.Identifying risk factors for the occurrence of serious adverse drug reactions (SADR) would allow a more individualized and safer drug therapy. SADR are rare events and therefore difficult to study. We tested the feasibility of a nested matched case-control study to examine the influence of high drug plasma levels and CYP2D6 genotypes on the risk to experience an SADR. In our sample we compared 62 SADR cases with 82 controls; both groups were psychiatric patients from the in-patient clinic Königsfelden. Drug plasma levels of >120% of the upper recommended references could be identified as a risk factor with a statistically significant odds ratio of 3.5, a similar trend could be seen for CYP2D6 poor metaboliser. Although a matched case-control design seems a valid method, 100% matching is not easy to perform in a relative small cohort of one in-patient clinic. However, a nested case-control study is feasible.On the base of the experience gained in the AMSP+ study and the fact that we have today only sparse data indicating that routine drug plasma concentration monitoring and/or pharmacogenetic testing in psychiatry are justified to minimize the risk for ADR, we developed a test algorithm named "TDM plus" (TDM plus interaction checks plus pharmacogenetic testing).Pharmacovigilance programs such as the AMSP project (AMSP = Arzneimittelsicherheit in der Psychiatrie) survey psychiatric in-patients in order to collect SADR and to detect new safety signals. Case reports of such SADR are, although anecdotal, valuable to illustrate rare clinical events and sometimes confirm theoretical assumptions of e.g. drug interactions. Seven pharmacovigilance case reports are summarized in this thesis.To provide clinicians with meaningful information on the risk of drug combinations, during the course of this thesis the internet based drug interaction program mediQ.ch (in German) has been developed. Risk estimation is based on published clinical and pharmacological information of single drugs and alimentary products, including adverse drug reaction profiles. Information on risk factors such as renal and hepatic insufficiency and specific genotypes are given. More than 20'000 drug pairs have been described in detail. Over 2000 substances with their metabolic and transport pathways are included and all information is referenced with links to the published scientific literature or other information sources. Medical professionals of more than 100 hospitals and 300 individual practitioners do consult mediQ.ch regularly. Validations with comparisons to other drug interaction programs show good results.Finally, therapeutic drug monitoring, drug interaction programs and pharmacogenetic tests are helpful tools in pharmacovigilance and should, in absence of sufficient routine tests supporting data, be used as proposed in our TDM plus algorithm.RESUMEPour améliorer la sécurité d'emploi des médicaments il est important de mieux comprendre leurs interactions dans le corps des patients. Ensuite le clinicien qui prescrit une pharmacothérapie doit avoir un accès simple à ces informations. Entre autres, cette thèse contribue à mieux connaître les caractéristiques pharmacocinétiques de deux médicaments. Elle examine aussi l'utilisation de trois outils en pharmacovigilance : le monitorage thérapeutique des taux plasmatiques des médicaments (« therapeutic drug monitoring »), un programme informatisé d'estimation du risque de combinaisons médicamenteuses, et enfin des tests pharmacogénétiques.Deux études cliniques pharmacogénétiques ont été conduites dans le cadre habituel de clinique psychiatrique : l'une avec la mirtazapine (antidépresseur), l'autre avec la clozapine (antipsychotique). On a traité 45 patients dépressifs avec de la mirtazapine pendant 8 semaines. L'effet thérapeutique était semblable à celui des études précédentes. Nous avons confirmé l'influence de l'âge et du sexe sur la pharmacocinétique de la mirtazapine et la différence dans les concentrations plasmatiques entre fumeurs et non-fumeurs. Au moyen d'analyses énantiomères sélectives, nous avons pu montrer une influence significative du génotype CYP2D6 sur l'énantiomère S+, principalement responsable de l'effet antidépresseur. Pour la première fois, nous avons trouvé une influence du génotype CYP2B6 sur les taux plasmatiques de la 8-OH-mirtazapine. Par ailleurs, le génotype CYP2B6*6/*6 était associé à une meilleure réponse thérapeutique. Une hypothèse sur les voies métaboliques détaillées de la mirtazapine est proposée. Dans la deuxième étude, 75 patients schizophrènes traités avec de la clozapine ont été examinés pour étudier l'influence des génotypes des iso-enzymes CYP450 et de la protéine de transport ABCB1 sur la pharmacocinétique de cet antipsychotique. Pour la première fois, on a montré in vivo un effet des génotypes CYP2C19 et ABCB1 sur les taux plasmatiques de la clozapine. L'importance du CYP1A2 dans le métabolisme de la clozapine a été confirmée.L'identification de facteurs de risques dans la survenue d'effets secondaire graves permettrait une thérapie plus individualisée et plus sûre. Les effets secondaires graves sont rares. Dans une étude de faisabilité (« nested matched case-control design » = étude avec appariement) nous avons comparé des patients avec effets secondaires graves à des patients-contrôles prenant le même type de médicaments mais sans effets secondaires graves. Des taux plasmatiques supérieurs à 120% de la valeur de référence haute sont associés à un risque avec « odds ratio » significatif de 3.5. Une tendance similaire est apparue pour le génotype du CYP2D6. Le « nested matched case-control design » semble une méthode valide qui présente cependant une difficulté : trouver des patients-contrôles dans le cadre d'une seule clinique psychiatrique. Par contre la conduite d'une « nested case-control study » sans appariement est recommandable.Sur la base de notre expérience de l'étude AMSP+ et le fait que nous disposons que de peux de données justifiant des monitorings de taux plasmatiques et/ou de tests pharmacogénétiques de routine, nous avons développé un test algorithme nommé « TDMplus » (TDM + vérification d'interactions médicamenteuses + tests pharmacogénétique).Des programmes de pharmacovigilances comme celui de l'AMSP (Arzneimittelsicherheit in der Psychiatrie = pharmacovigilance en psychiatrie) collectent les effets secondaires graves chez les patients psychiatriques hospitalisés pour identifier des signaux d'alertes. La publication de certains de ces cas même anecdotiques est précieuse. Elle décrit des événements rares et quelques fois une hypothèse sur le potentiel d'une interaction médicamenteuse peut ainsi être confirmée. Sept publications de cas sont résumées ici.Dans le cadre de cette thèse, on a développé un programme informatisé sur internet (en allemand) - mediQ.ch - pour estimer le potentiel de risques d'une interaction médicamenteuse afin d'offrir en ligne ces informations utiles aux cliniciens. Les estimations de risques sont fondées sur des informations cliniques (y compris les profils d'effets secondaires) et pharmacologiques pour chaque médicament ou substance combinés. Le programme donne aussi des informations sur les facteurs de risques comme l'insuffisance rénale et hépatique et certains génotypes. Actuellement il décrit en détail les interactions potentielles de plus de 20'000 paires de médicaments, et celles de 2000 substances actives avec leurs voies de métabolisation et de transport. Chaque information mentionne sa source d'origine; un lien hypertexte permet d'y accéder. Le programme mediQ.ch est régulièrement consulté par les cliniciens de 100 hôpitaux et par 300 praticiens indépendants. Les premières validations et comparaisons avec d'autres programmes sur les interactions médicamenteuses montrent de bons résultats.En conclusion : le monitorage thérapeutique des médicaments, les programmes informatisés contenant l'information sur le potentiel d'interaction médicamenteuse et les tests pharmacogénétiques sont de précieux outils en pharmacovigilance. Nous proposons de les utiliser en respectant l'algorithme « TDM plus » que nous avons développé.

Quantification of 4 antidepressants and a metabolite by LC-MS for therapeutic drug monitoring.

A liquid chromatography method coupled to mass spectrometry was developed for the quantification of bupropion, its metabolite hydroxy-bupropion, moclobemide, reboxetine and trazodone in human plasma. The validation of the analytical procedure was assessed according to Société Française des Sciences et Techniques Pharmaceutiques and the latest Food and Drug Administration guidelines. The sample preparation was performed with 0.5mL of plasma extracted on a cation-exchange solid phase 96-well plate. The separation was achieved in 14min on a C18 XBridge column (2.1mm×100mm, 3.5μm) using a 50mM ammonium acetate pH 9/acetonitrile mobile phase in gradient mode. The compounds of interest were analysed in the single ion monitoring mode on a single quadrupole mass spectrometer working in positive electrospray ionisation mode. Two ions were selected per molecule to increase the number of identification points and to avoid as much as possible any false positives. Since selectivity is always a critical point for routine therapeutic drug monitoring, more than sixty common comedications for the psychiatric population were tested. For each analyte, the analytical procedure was validated to cover the common range of concentrations measured in plasma samples: 1-400ng/mL for reboxetine and bupropion, 2-2000ng/mL for hydroxy-bupropion, moclobemide, and trazodone. For all investigated compounds, reliable performance in terms of accuracy, precision, trueness, recovery, selectivity and stability was obtained. One year after its implementation in a routine process, this method demonstrated a high robustness with accurate values over the wide concentration range commonly observed among a psychiatric population.

Quantification of typical antipsychotics in human plasma by ultra-high performance liquid chromatography tandem mass spectrometry for therapeutic drug monitoring.

A selective and sensitive method was developed for the simultaneous quantification of seven typical antipsychotic drugs (cis-chlorprothixene, flupentixol, haloperidol, levomepromazine, pipamperone, promazine and zuclopenthixol) in human plasma. Ultra-high performance liquid chromatography (UHPLC) was used for complete separation of the compounds in less than 4.5min on an Acquity UPLC BEH C18 column (2.1mm×50mm; 1.7μm), with a gradient elution of ammonium formate buffer pH 4.0 and acetonitrile at a flow rate of 400μl/min. Detection was performed on a tandem quadrupole mass spectrometer (MS/MS) equipped with an electrospray ionization interface. A simple protein precipitation procedure with acetonitrile was used for sample preparation. Thanks to the use of stable isotope-labeled internal standards for all analytes, internal standard-normalized matrix effects were in the range of 92-108%. The method was fully validated to cover large concentration ranges of 0.2-90ng/ml for haloperidol, 0.5-90ng/ml for flupentixol, 1-450ng/ml for levomepromazine, promazine and zuclopenthixol and 2-900ng/ml for cis-chlorprothixene and pipamperone. Trueness (89.1-114.8%), repeatability (1.8-9.9%), intermediate precision (1.9-16.3%) and accuracy profiles (<30%) were in accordance with the latest international recommendations. The method was successfully used in our laboratory for routine quantification of more than 500 patient plasma samples for therapeutic drug monitoring. To the best of our knowledge, this is the first UHPLC-MS/MS method for the quantification of the studied drugs with a sample preparation based on protein precipitation.

Monitoring of illicit pill distribution networks using an image collection exploration framework

This paper proposes a novel approach for the analysis of illicit tablets based on their visual characteristics. In particular, the paper concentrates on the problem of ecstasy pill seizure profiling and monitoring. The presented method extracts the visual information from pill images and builds a representation of it, i.e. it builds a pill profile based on the pill visual appearance. Different visual features are used to build different image similarity measures, which are the basis for a pill monitoring strategy based on both discriminative and clustering models. The discriminative model permits to infer whether two pills come from the same seizure, while the clustering models groups of pills that share similar visual characteristics. The resulting clustering structure allows to perform a visual identification of the relationships between different seizures. The proposed approach was evaluated using a data set of 621 Ecstasy pill pictures. The results demonstrate that this is a feasible and cost effective method for performing pill profiling and monitoring.

Non-invasive monitoring of diaphragmatic timing by means of surface contact sensors: an experimental study in dogs

Background: Non-invasive monitoring of respiratory muscle function is an area of increasing research interest, resulting in the appearance of new monitoring devices, one of these being piezoelectric contact sensors. The present study was designed to test whether the use of piezoelectric contact (non-invasive) sensors could be useful in respiratory monitoring, in particular in measuring the timing of diaphragmatic contraction.Methods: Experiments were performed in an animal model: three pentobarbital anesthetized mongrel dogs. The motion of the thoracic cage was acquired by means of a piezoelectric contact sensor placed on the costal wall. This signal is compared with direct measurements of the diaphragmatic muscle length, made by sonomicrometry. Furthermore, to assess the diaphragmatic function other respiratory signals were acquired: respiratory airflow and transdiaphragmatic pressure. Diaphragm contraction time was estimated with these four signals. Using diaphragm length signal as reference, contraction times estimated with the other three signals were compared with the contraction time estimated with diaphragm length signal.Results: The contraction time estimated with the TM signal tends to give a reading 0.06 seconds lower than the measure made with the DL signal (-0.21 and 0.00 for FL and DP signals, respectively), with a standard deviation of 0.05 seconds (0.08 and 0.06 for FL and DP signals, respectively). Correlation coefficients indicated a close link between time contraction estimated with TM signal and contraction time estimated with DL signal (a Pearson correlation coefficient of 0.98, a reliability coefficient of 0.95, a slope of 1.01 and a Spearman's rank-order coefficient of 0.98). In general, correlation coefficients and mean and standard deviation of the difference were better in the inspiratory load respiratory test than in spontaneous ventilation tests.Conclusion: The technique presented in this work provides a non-invasive method to assess the timing of diaphragmatic contraction in canines, using a piezoelectric contact sensor placed on the costal wall.

Dosage plasmatique des medicaments antidépresseurs [Recommendations for therapeutic monitoring of antidepressants].

Therapeutic drug monitoring (TDM), combined in certain situations with pharmacogenetic tests of metabolism, has proven a valuable tool for psychopharmacotherapy. Uncertain drug adherence, suboptimal tolerability, nonresponse at therapeutic doses, or pharmacokinetic drug-drug interactions are typical situations when measurement of medication concentrations is helpful. This article is an adaptation of guidelines recently issued by the AGNP-TDM group (Hiemke et al., www. agnp.de), but its content focuses mainly on the TDM of antidepressants. Finally, the potential benefits of TDM for optimization of pharmacotherapy can only be obtained if the method is adequately integrated into the clinical treatment process.

Monitoring the effects of adult psychotherapy in routine practice in Switzerland: A feasibility trial

Background: Several studies have been published on the effects of psychotherapy in routine practice. Complementing traditional views summarised as 'dose-effect models', Stiles et al. put forward data consistent with the responsive regulation model underlining the importance of the client's active participant role in defining length of treatment. One may ask what level of change reached by a patient is considered to be the 'good enough level' (GEL) and if it is related to the duration of psychotherapy. Aims: The main objective of the present feasibility trial was to monitor the patient's session-by-session evolution using a self-report questionnaire in order to define the GEL, i.e. the number of sessions necessary for the patient to reach significant change. Method: A total of N=13 patients undergoing psychotherapy in routine practice participated in the study, completing the Outcome Questionnaire - 45.2 (OQ-45), which assesses the symptom level, interpersonal relationships and social role after every psychotherapy session. The data was analysed using multi-level analyses (HLMs). Results: High feasibility of fine-grained assessment of effects of psychotherapy in routine practice in Switzerland was shown; response rates being acceptable; however, detailed analysis of the GEL was not feasible within the short study time-frame. Conclusions: Reflections on the political context of monitoring in the specific case of routine psychiatric practice in Switzerland are discussed.

Monitoring of the Launched Girder Bridge over the Iowa River on US 20, March 2004

The objective of the study presented in this report was to document the launch of the Iowa River Bridge and to monitor and evaluate the structural performance of the bridge superstructure and substructure during the launch. The Iowa Department of Transportation used an incremental launching method, which is relatively unique for steel I-girder bridges, to construct the Iowa River Bridge over an environmentally sensitive river valley in central Iowa. The bridge was designed as two separate roadways consisting of four steel plate girders each that are approximately 11 ft deep and span approximately 301 ft each over five spans. The concrete bridge deck was not placed until after both roadways had been launched. One of the most significant monitoring and evaluation observations related to the superstructure was that the bottom flange (and associated web region) was subjected to extremely large stresses during the crossing of launch rollers. Regarding the substructure performance, the column stresses did not exceed reasonable design limits during the daylong launches. The scope of the study did not allow adequate quantification of the measured applied launch forces at the piers. Future proposed esearch should provide an opportunity to address this. The overall experimental performance of the bridge during the launch was compared with the predicted design performance. In general, the substructure design, girder contact stress, and total launching force assumptions correlated well with the experimental results. The design assumptions for total axial force in crossframe members, on the other hand, differed from the experimental results by as much as 300%.

Simultaneous determination of antidementia drugs by HPLC-MS: validation data of the method and plasma level determinations in 300 patients

Aims: A rapid and simple HPLC-MS method was developed for the simultaneousdetermination of antidementia drugs, including donepezil, galantamine, rivastigmineand its major metabolite NAP 226 - 90, and memantine, for TherapeuticDrug Monitoring (TDM). In the elderly population treated with antidementiadrugs, the presence of several comorbidities, drug interactions resulting frompolypharmacy, and variations in drug metabolism and elimination, are possiblefactors leading to the observed high interindividual variability in plasma levels.Although evidence for the benefit of TDM for antidementia drugs still remains tobe demonstrated, an individually adapted dosage through TDM might contributeto minimize the risk of adverse reactions and to increase the probability of efficienttherapeutic response. Methods: A solid-phase extraction procedure with amixed-mode cation exchange sorbent was used to isolate the drugs from 0.5 mL ofplasma. The compounds were analyzed on a reverse-phase column with a gradientelution consisting of an ammonium acetate buffer at pH 9.3 and acetonitrile anddetected by mass spectrometry in the single ion monitoring mode. Isotope-labeledinternal standards were used for quantification where possible. The validatedmethod was used to measure the plasma levels of antidementia drugs in 300patients treated with these drugs. Results: The method was validated accordingto international standards of validation, including the assessment of the trueness(-8 - 11 %), the imprecision (repeatability: 1-5%, intermediate imprecision:2 - 9 %), selectivity and matrix effects variability (less than 6 %). Furthermore,short and long-term stability of the analytes in plasma was ascertained. Themethod proved to be robust in the calibrated ranges of 1 - 300 ng/mL for rivastigmineand memantine and 2 - 300 mg/mL for donepezil, galantamine and NAP226 - 90. We recently published a full description of the method (1). We found ahigh interindividual variability in plasma levels of these drugs in a study populationof 300 patients. The plasma level measurements, with some preliminaryclinical and pharmacogenetic results, will be presented. Conclusion: A simpleLC-MS method was developed for plasma level determination of antidementiadrugs which was successfully used in a clinical study with 300 patients.

Ambulatory blood pressure monitoring: a mean to stratify cardiovascular risk.

OBJECTIVE: Current hypertension guidelines stress the importance to assess total cardiovascular risk but do not describe precisely how to use ambulatory blood pressures in the cardiovascular risk stratification. METHOD: We calculated here global cardiovascular risk according to 2003 European Society of Hypertension/European Society of Cardiology guidelines in 127 patients in whom daytime ambulatory blood pressures were recorded and carotid/femoral ultrasonography performed. RESULTS: The presence of ambulatory blood pressures >or =135/85 mmHg shifted cardiovascular risk to higher categories, as did the presence of hypercholesterolemia and, even more so, the presence of atherosclerotic plaques. CONCLUSION: Further studies are, however, needed to define the position of ambulatory blood pressures in the assessment of cardiovascular risk.

Spatial evaluation of larvae of Culicidae (Diptera) from different breeding sites: application of a geospatial method and implications for vector control

Spatial evaluation of Culicidae (Diptera) larvae from different breeding sites: application of a geospatial method and implications for vector control. This study investigates the spatial distribution of urban Culicidae and informs entomological monitoring of species that use artificial containers as larval habitats. Collections of mosquito larvae were conducted in the São Paulo State municipality of Santa Bárbara d' Oeste between 2004 and 2006 during house-to-house visits. A total of 1,891 samples and nine different species were sampled. Species distribution was assessed using the kriging statistical method by extrapolating municipal administrative divisions. The sampling method followed the norms of the municipal health services of the Ministry of Health and can thus be adopted by public health authorities in disease control and delimitation of risk areas. Moreover, this type of survey and analysis can be employed for entomological surveillance of urban vectors that use artificial containers as larval habitat.

Simple and fast methods based on solid-phase extraction coupled to liquid chromatography with UV detection for the monitoring of caffeine in natural and waste waters as marker of anthropogenic impact

Two concentration methods for fast and routine determination of caffeine (using HPLC-UV detection) in surface, and wastewater are evaluated. Both methods are based on solid-phase extraction (SPE) concentration with octadecyl silica sorbents. A common “offline” SPE procedure shows that quantitative recovery of caffeine is obtained with 2 mL of an elution mixture solvent methanol-water containing at least 60% methanol. The method detection limit is 0.1 μg L−1 when percolating 1 L samples through the cartridge. The development of an “online” SPE method based on a mini-SPE column, containing 100 mg of the same sorbent, directly connected to the HPLC system allows the method detection limit to be decreased to 10 ng L−1 with a sample volume of 100 mL. The “offline” SPE method is applied to the analysis of caffeine in wastewater samples, whereas the “on-line” method is used for analysis in natural waters from streams receiving significant water intakes from local wastewater treatment plants