Semiautomatic interictal electric source localization based on long-term electroencephalographic monitoring: A prospective study.

OBJECTIVE: Electric source imaging (ESI) of interictal epileptiform discharges (IEDs) has shown significant yield in numerous studies; however, its implementation at most centers is labor- and cost-intensive. Semiautomatic ESI analysis (SAEA) has been proposed as an alternative and has previously shown benefit. Computer-assisted automatic spike cluster retrieval, averaging, and source localization are carried out for each cluster and are then reviewed by an expert neurophysiologist, to determine their relevance for the individual case. Here, we examine its yield in a prospective single center study. METHOD: Between 2017 and 2022, 122 patients underwent SAEA. Inclusion criteria for the current study were unifocal epilepsy disorder, epilepsy surgery with curative purpose, and postoperative follow-up of 2 years or more. All patients (N=40) had continuous video-electroencephalographic (EEG) monitoring with 37 scalp electrodes, which underwent SAEA. Forty patients matched our inclusion criteria. RESULTS: Twenty patients required intracranial monitoring; 13 were magnetic resonance imaging (MRI)-negative. Mean duration of analyzed EEG was 4.3 days (±3.1 days), containing a mean of 12 749 detected IEDs (±22 324). The sensitivity, specificity, and accuracy of SAEA for localizing the epileptogenic focus of the entire group were 74.3%, 80%, and 75%, respectively, leading to an odds ratio (OR) of 11.5 to become seizure-free if the source was included in the resection volume (p < .05). In patients with extratemporal lobe epilepsy, our results indicated an accuracy of 68% (OR=11.7). For MRI-negative patients (n = 13) and patients requiring intracranial EEG (n = 20), we found a similarly high accuracy of 84.6% (OR=19) and 75% (OR = 15.9), respectively. SIGNIFICANCE: In this prospective study of SAEA of long-term video-EEG, spanning several days, we found excellent localizing information and a high yield, even in difficult patient groups. This compares favorably to high-density ESI, most likely due to marked improved signal-to-noise ratio of the averaged IEDs. We propose including ESI, or SAEA, in the workup of all patients who are referred for epilepsy surgery.

Detection of interictal epileptiform discharges in an extended scalp EEG array and high-density EEG-A prospective multicenter study.

OBJECTIVES: High counts of averaged interictal epileptiform discharges (IEDs) are key components of accurate interictal electric source imaging (ESI) in patients with focal epilepsy. Automated detections may be time-efficient, but they need to identify the correct IED types. Thus we compared semiautomated and automated detection of IED types in long-term video-EEG (electroencephalography) monitoring (LTM) using an extended scalp EEG array and short-term high-density EEG (hdEEG) with visual detection of IED types and the seizure-onset zone (SOZ). METHODS: We prospectively recruited consecutive patients from four epilepsy centers who underwent both LTM with 40-electrode scalp EEG and short-term hdEEG with 256 electrodes. Only patients with a single circumscribed SOZ in LTM were included. In LTM and hdEEG, IED types were identified visually, semiautomatically and automatically. Concordances of semiautomated and automated detections in LTM and hdEEG, as well as visual detections in hdEEG, were compared against visually detected IED types and the SOZ in LTM. RESULTS: Fifty-two of 62 patients with LTM and hdEEG were included. The most frequent IED types per patient, detected semiautomatically and automatically in LTM and visually in hdEEG, were significantly concordant with the most frequently visually identified IED type in LTM and the SOZ. Semiautomated and automated detections of IED types in hdEEG were significantly concordant with visually identified IED types in LTM, only when IED types with more than 50 detected single IEDs were selected. The threshold of 50 detected IED in hdEEG was reached in half of the patients. For all IED types per patient, agreement between visual and semiautomated detections in LTM was high. SIGNIFICANCE: Semiautomated and automated detections of IED types in LTM show significant agreement with visually detected IED types and the SOZ. In short-term hdEEG, semiautomated detections of IED types are concordant with visually detected IED types and the SOZ in LTM if high IED counts were detected.

Distributed Sensor Coordination Algorithms for Efficient Coverage in a Network of Heterogeneous Mobile Sensors.

The main focus of this work is directed towards distributed coordination algorithms for coverage in a mobile sensor network. The sensors are assumed to have nonidentical sensing ranges, and it is desired to move them in such a way that the total sensing coverage increases as much as possible. To this end, the field is partitioned using the multiplicatively weighted Voronoi cells, and then different geometric methods are developed to find new locations for the sensors such that the coverage is improved. The proposed algorithms are iterative, and use the available local information to place the sensors properly, aiming to reduce the size of the coverage holes in the network. Simulations demonstrate the good performance of the proposed algorithms.

Maximum Lifetime Strategy for Target Monitoring with Controlled Node Mobility in Sensor Networks with Obstacles.

In this paper, an efficient technique is proposed for a mobile sensor network used to monitor a moving target in a field with obstacles while the network lifetime is maximized. The main sources of energy consumption of the sensors in the network are sensing, communication, and movement. A graph is constructed and its edges are weighted properly based on the remaining energy of each sensor. This graph is subsequently employed to address the lifetime maximization problem by solving a sequence of shortest path problems, which can be solved using existing methods. The proposed technique determines a near-optimal relocation strategy for the sensors as well as an energy-efficient route to transfer information from the target to destination. This near-optimal solution is calculated in every time instant, using the information of the previous time step. It is shown that by choosing appropriate parameters, sensors' locations and the communication route from target to destination obtained by the proposed algorithm can be arbitrarily close to the optimal locations and route at each time instant. Simulation results confirm the effectiveness of the proposed technique.

Toward Autonomous Mobile Sensor Networks Technology.

Mobile sensor networking technology has attracted considerable attention in various research communities in recent years due to their widespread applications in civilian and military environments. One objective when using mobile sensors is to obtain maximum field coverage by properly deploying sensor nodes. In many real-world applications a priori knowledge about the best deployment position for the sensors is not available. However, the motion capability of the sensors could allow each node to adjust its position (i.e. relocate) so that a better (and ultimately maximal) coverage is achieved. In this paper, a novel autonomous joint sensing range and relocation control algorithm is presented that achieves improved coverage and network lifetime at the same time. In the proposed algorithm, the sensing range of each sensor is adjusted iteratively based on its residual energy. At the same time, the sensor is directed to move within its corresponding multiplicatively weighted Voronoi (MW-Voronoi) region to ultimately increase sensing coverage in the field. Simulation results demonstrate the efficacy of the technique.

Exploring predictors of COVID-19 precautionary behaviors during the initial rollout of COVID-19 vaccines in a predominately Hispanic sample.

•Precautionary behaviors were lower if primary language in household was Spanish.•Testing positive for COVID-19 was inversely associated with precautionary behaviors.•Healthcare practitioners were the most trusted source of COVID-19 information.

Subclinical epileptiform activity in the Alzheimer continuum: association with disease, cognition and detection method.

BACKGROUND: Epileptic seizures are an established comorbidity of Alzheimer's disease (AD). Subclinical epileptiform activity (SEA) as detected by 24-h electroencephalography (EEG) or magneto-encephalography (MEG) has been reported in temporal regions of clinically diagnosed AD patients. Although epileptic activity in AD probably arises in the mesial temporal lobe, electrical activity within this region might not propagate to EEG scalp electrodes and could remain undetected by standard EEG. However, SEA might lead to faster cognitive decline in AD. AIMS: 1. To estimate the prevalence of SEA and interictal epileptic discharges (IEDs) in a well-defined cohort of participants belonging to the AD continuum, including preclinical AD subjects, as compared with cognitively healthy controls. 2. To evaluate whether long-term-EEG (LTM-EEG), high-density-EEG (hd-EEG) or MEG is superior to detect SEA in AD. 3. To characterise AD patients with SEA based on clinical, neuropsychological and neuroimaging parameters. METHODS: Subjects (n = 49) belonging to the AD continuum were diagnosed according to the 2011 NIA-AA research criteria, with a high likelihood of underlying AD pathophysiology. Healthy volunteers (n = 24) scored normal on neuropsychological testing and were amyloid negative. None of the participants experienced a seizure before. Subjects underwent LTM-EEG and/or 50-min MEG and/or 50-min hd-EEG to detect IEDs. RESULTS: We found an increased prevalence of SEA in AD subjects (31%) as compared to controls (8%) (p = 0.041; Fisher's exact test), with increasing prevalence over the disease course (50% in dementia, 27% in MCI and 25% in preclinical AD). Although MEG (25%) did not withhold a higher prevalence of SEA in AD as compared to LTM-EEG (19%) and hd-EEG (19%), MEG was significantly superior to detect spikes per 50 min (p = 0.002; Kruskall-Wallis test). AD patients with SEA scored worse on the RBANS visuospatial and attention subset (p = 0.009 and p = 0.05, respectively; Mann-Whitney U test) and had higher left frontal, (left) temporal and (left and right) entorhinal cortex volumes than those without. CONCLUSION: We confirmed that SEA is increased in the AD continuum as compared to controls, with increasing prevalence with AD disease stage. In AD patients, SEA is associated with more severe visuospatial and attention deficits and with increased left frontal, (left) temporal and entorhinal cortex volumes. TRIAL REGISTRATION: Clinicaltrials.gov, NCT04131491. 12/02/2020.

Injection of vascular endothelial growth factor into knee joints induces osteoarthritis in mice.

UNLABELLED: Osteoarthritis (OA) is a common joint disorder affecting circa 2% of the population. OBJECTIVES: It has been suggested that secretion of vascular endothelial growth factor (VEGF) could play a role in the chain of events leading to OA. METHODS: In the present study, healthy mice were injected intra-articularly with VEGF. RESULTS: Shortly after the administration of VEGF, synovial hyperplasia, increased calcification of the articular cartilage and bone sclerosis were observed. Consequently, cartilage degradation characteristic of OA was found. These changes were seen to a lesser degree in the opposite knees of VEGF-injected mice and did not occur in the control mice. CONCLUSIONS: The findings suggest an active role of VEGF in the pathogenesis of OA and render support to a possible role for subchondral bone sclerosis in the pathogenesis of cartilage degradation.

Polymer translocation in solid-state nanopores: dependence of scaling behavior on pore dimensions and applied voltage.

We investigate unforced and forced translocation of a Rouse polymer (in the absence of hydrodynamic interactions) through a silicon nitride nanopore by three-dimensional Langevin dynamics simulations, as a function of pore dimensions and applied voltage. Our nanopore model consists of an atomistically detailed nanopore constructed using the crystal structure of ß-Si(3)N(4). We also use realistic parameters in our simulation models rather than traditional dimensionless quantities. When the polymer length is much larger than the pore length, we find the translocation time versus chain length scales as τ ∼ N(2+ν) for the unforced case and as τ ∼ N((1+2ν)/(1+ν)) for the forced case. Our results agree with theoretical predictions which indicate that memory effects and tension on the polymer chain play an important role during the translocation process. We also find that the scaling exponents are highly dependent on the applied voltage (force). When the length of the polymer is on the order of the length of the pore, we do not find a continuous scaling law, but rather scaling exponents that increase as the length of the polymer increases. Finally, we investigate the scaling behavior of translocation time versus applied voltage for different polymer and pore lengths. For long pores, we obtain the theoretical scaling law of τ ∼ 1/V(α), where α ≅ 1 for all voltages and polymer lengths. For short pores, we find that α decreases for very large voltages and/or small polymer lengths, indicating that the value of α = 1 is not universal. The results of our simulations are discussed in the context of experimental measurements made under different conditions and with differing pore geometries.

Automated ictal EEG source imaging: A retrospective, blinded clinical validation study.

OBJECTIVE: EEG source imaging (ESI) is a validated tool in the multimodal workup of patients with drug resistant focal epilepsy. However, it requires special expertise and it is underutilized. To circumvent this, automated analysis pipelines have been developed and validated for the interictal discharges. In this study, we present the clinical validation of an automated ESI for ictal EEG signals. METHODS: We have developed an automated analysis pipeline of ictal EEG activity, based on spectral analysis in source space, using an individual head model of six tissues. The analysis was done blinded to all other data. As reference standard, we used the concordance with the resected area and one-year postoperative outcome. RESULTS: We analyzed 50 consecutive patients undergoing epilepsy surgery (34 temporal and 16 extra-temporal). Thirty patients (60%) became seizure-free. The accuracy of the automated ESI was 74% (95% confidence interval: 59.66-85.37%). CONCLUSIONS: Automated ictal ESI has a high accuracy for localizing the seizure onset zone. SIGNIFICANCE: Automating the ESI of the ictal EEG signals will facilitate implementation of this tool in the presurgical evaluation.

Automated interictal source localisation based on high-density EEG.

PURPOSE: To study the accuracy of automated interictal EEG source localisation based on high-density EEG, and to compare it to low-density EEG. METHODS: Thirty patients operated for pharmacoresistant focal epilepsy were retrospectively examined. Twelve months after resective brain surgery, 18 were seizure-free or had 'auras' only, while 12 had persistence of disabling seizures. Presurgical 257-channel EEG lasting 3-20 h was down-sampled to 25, 40, and 204 channels for separate analyses. For each electrode setup, interictal spikes were detected, clustered, and averaged automatically before validation by an expert reviewer. An individual 6-layer finite difference head model and the standardised low-resolution electromagnetic tomography were used to localise the maximum source activity of the most prevalent spike. Sublobar concordance with the resected brain area was visually assessed and related to favourable vs. unfavourable postsurgical outcome. RESULTS: Depending on the EEG setup, epileptic spikes were detected in 21-24 patients (70-80%). The median number of single spikes per average was 470 (range 17-15,066). Diagnostic sensitivity of EEG source localisation was 58-75%, specificity was 50-67%, and overall accuracy was 55-71%. There were no significant differences between low- and high-density EEG setups with 25 to 257 electrodes. CONCLUSION: Automated high-density EEG source localisation provides meaningful information in the majority of cases. With hundreds of single spikes averaged, diagnostic accuracy is similar in high- and low-density EEG. Therefore, low-density EEG may be sufficient for interictal EEG source localisation if high numbers of spikes are available.

Automated electrical source imaging with scalp EEG to define the insular irritative zone: Comparison with simultaneous intracranial EEG.

OBJECTIVE: To evaluate the accuracy of automatedinterictallow-density electrical source imaging (LD-ESI) to define the insular irritative zone (IZ) by comparing the simultaneous interictal ESI localization with the SEEG interictal activity. METHODS: Long-term simultaneous scalp electroencephalography (EEG) and stereo-EEG (SEEG) with at least one depth electrode exploring the operculo-insular region(s) were analyzed. Automated interictal ESI was performed on the scalp EEG using standardized low-resolution brain electromagnetic tomography (sLORETA) and individual head models. A two-step analysis was performed: i) sublobar concordance betweencluster-based ESI localization and SEEG-based IZ; ii) time-locked ESI-/SEEG analysis. Diagnostic accuracy values were calculated using SEEG as reference standard. Subgroup analysis wascarried out, based onthe involvement of insular contacts in the seizure onset and patterns of insular interictal activity. RESULTS: Thirty patients were included in the study. ESI showed an overall accuracy of 53% (C.I. 29-76%). Sensitivity and specificity were calculated as 53% (C.I. 29-76%), 55% (C.I. 23-83%) respectively. Higher accuracy was found in patients with frequent and dominant interictal insular spikes. CONCLUSIONS: LD-ESI defines with good accuracy the insular implication in the IZ, which is not possible with classical interictalscalpEEG interpretation. SIGNIFICANCE: Automated LD-ESI may be a valuable additional tool to characterize the epileptogenic zone in epilepsies with suspected insular involvement.

Fetal programming in sheep: effects on pre- and postnatal development in lambs.

This systematic review and meta-analysis aim to summarize the effects of maternal undernutrition or overnutrition during pregnancy on fetal weight and morphometric measurements during pregnancy, at birth, and postnatal period in sheep. After completing the search, selection, and data extraction steps, the measure of effect was generated by the individual comparison of each indicator with the average of the control and treated group (undernutrition or overnutrition) using the DerSimonian and Laird method for random effects. Subgroup analyses were also performed for lambing order, litter size, sex, as well as level, timing, and duration of the intervention. Fetal weight during the first third of pregnancy was not affected by maternal undernutrition or overnutrition. On the other hand, undernutrition in the second and last third of gestation reduces the weight of the lamb both during pregnancy, at birth, and during the postnatal period, requiring at least 120 postnatal days to achieve the same weight as its contemporaries in the control treatment. However, this reduction in weight is not accompanied by reductions in morphometric measurements, demonstrating that the animals were lighter, but of equal size. In overnutrition, there is an increase in fetal weight in the second third of gestation. However, in the last third of the gestational period, there are no differences in fetal weight for the multiparous subgroup, but it was reduced in primiparous ewes. There are no effects of overnutrition on birth weight; however, this result is highly heterogeneous. Thus, maternal nutrition of ewe during pregnancy has effects on fetal and postnatal weight, but not on size. Furthermore, the effects of undernutrition are more homogeneous while overnutrition showed heterogeneous responses.

Ictal EEG source imaging and connectivity to localize the seizure onset zone in extratemporal lobe epilepsy.

PURPOSE: To evaluate the yield of Functional Connectivity (FC) in addition to low-density ictal Electrical Source Imaging (ESI) in extratemporal lobe epilepsy (ETLE), using an automated algorithm for analysis. METHOD: Long-term EEG monitoring of consecutive ETLE patients who underwent surgery was reviewed by epileptologists, and seizure onsets characterized by rhythmical activity were identified. A spectrogram-based algorithm was developed to select objectively the parameters of ESI analysis. Two methods for SOZ localization were compared: i) ESI power, based on LORETA exclusively; ii) ESI + FC, including a Granger causality-based connectivity analysis. Results were determined at a sublobar level. The resection zone, in relation to 1-year follow-up surgical outcome, was considered as reference standard for diagnostic accuracy analyses. RESULTS: Ninety-four seizures from 24 patients were analyzed. At seizure-level, ESI power showed 36 % sensitivity and 72 % specificity (accuracy: 45 %). ESI + FC significantly improved the accuracy, with 52 % sensitivity and 84 % specificity (accuracy: 61 %, p = 0.04). Results of ESI + FC were equally valuable in patients with lateralized or bilateral/generalized visual interpretation of ictal EEG. In a patient level sub-analysis, upon blinded clinical interpretation, ESI + FC showed a correct localization in 67 % of patients and substantial inter-rater agreement (kappa = 0.64), against 27 % achieved by ESI power, with fair inter-rater agreement (kappa = 0.37). CONCLUSION: FC significantly improves SOZ localization compared to ESI solely in ETLE. Ictal ESI + FC could represent a novel option in the armamentarium of presurgical evaluation, aiding also in patients with visually non-localizable scalp ictal EEG. Prospective studies evaluating the clinical added value of automated low-density ictal ESI may be justified.

A new universal high-performance liquid chromatographic method for determination of 1,4-benzodiazepines as bulk drugs and in pharmaceutical formulations.

A universal high-performance liquid chromatographic method was developed for the simultaneous determination of seven frequently prescribed 1,4-benzodiazepines in bulk powder or formulated in tablets or capsules. Peak tailing commonly reported with HPLC method developed for benzodiazepines, is completely omitted with this new method. The assay procedure consisted of pulverization, extraction into methanol, filtering, diluting and injecting of aliquots of clear filtrate into a reversed phase column with a very low silanol activity. The mobile phase consisted of a mixture of methanol and 0.05 mol x L(-1) buffer solution of ammonium dihydrogen phosphate (50:50, v/v) adjusted to pH 5.8. The effluent was monitored by UV detection at 254 nm and delivered at a flow rate of 1.6 mL x min(-1). The new method has been applied for quantifying of 1,4-benzodiazepines in different commercial formulations with recoveries ranging from 99.0 (+/- 1.98) to 102.0 (+/- 1.58)%. The excipients present in tablets and capsules did not interfere with the developed method. The applicability of the method for content uniformity and dissolution tests has been also investigated and the results were considered satisfactory. The developed method is rapid and sensitive, and is suitable for routine control of pharmaceutical dosage forms.

Automated EEG source imaging: A retrospective, blinded clinical validation study.

OBJECTIVE: To evaluate the accuracy of automated EEG source imaging (ESI) in localizing epileptogenic zone. METHODS: Long-term EEG, recorded with the standard 25-electrode array of the IFCN, from 41 consecutive patients with focal epilepsy who underwent resective surgery, were analyzed blinded to the surgical outcome. The automated analysis comprised spike-detection, clustering and source imaging at the half-rising time and at the peak of each spike-cluster, using individual head-models with six tissue-layers and a distributed source model (sLORETA). The fully automated approach presented ESI of the cluster with the highest number of spikes, at the half-rising time. In addition, a physician involved in the presurgical evaluation of the patients, evaluated the automated ESI results (up to four clusters per patient) in clinical context and selected the dominant cluster and the analysis time-point (semi-automated approach). The reference standard was location of the resected area and outcome one year after operation. RESULTS: Accuracy was 61% (95% CI: 45-76%) for the fully automated approach and 78% (95% CI: 62-89%) for the semi-automated approach. CONCLUSION: Automated ESI has an accuracy similar to previously reported neuroimaging methods. SIGNIFICANCE: Automated ESI will contribute to increased utilization of source imaging in the presurgical evaluation of patients with epilepsy.

Technical evaluation of radiation dose delivered in prostate cancer patients as measured by an implantable MOSFET dosimeter.

PURPOSE: To perform a comparison of the daily measured dose at depth in tissue with the predicted dose values from treatment plans for 29 prostate cancer patients involved in a clinical trial. METHODS AND MATERIALS: Patients from three clinical sites were implanted with one or two dosimeters in or near the prostatic capsule. The implantable device, known as the DVS, is based on a metal-oxide-semiconductor field effect transistor (MOSFET) detector. A portable telemetric readout system couples to the dosimeter antenna (visible on kilovoltage, computed tomography, and ultrasonography) for data transfer. The predicted dose values were determined by the location of the MOSFET on the treatment planning computed tomography scan. Serial computed tomography images were taken every 2 weeks to evaluate any migration of the device. The clinical protocol did not permit alteration of the treatment parameters using the dosimeter readings. For some patients, one of several image-guided radiotherapy (RT) modalities was used for target localization. RESULTS: The evaluation of dose discrepancy showed that in many patients the standard deviation exceeded the previous values obtained for the dosimeter in a phantom. In some patients, the cumulative dose disagreed with the planned dose by > or =5%. The data presented suggest that an implantable dosimeter can help identify dose discrepancies (random or systematic) for patients treated with external beam RT and could be used as a daily treatment verification tool for image-guided RT and adaptive RT. CONCLUSION: The results of our study have shown that knowledge of the dose delivered per fraction can potentially prevent over- or under-dosage to the treatment area and increase the accuracy of RT. The implantable dosimeter could also be used as a localizer for image-guided RT.

New high-performance liquid chromatographic method for serum analysis of oxazepam: application to bioequivalence and pharmacokinetic study.

A rapid and sensitive high-performance liquid chromatographic method was developed and validated for determination of oxazepam in serum. Oxazepam was isolated from biological fluid using a simple liquid-liquid extraction with dichloromethane. Nordazepam was used as the internal standard. The chromatographic separation was accomplished using a 125 x 4-mm (inner diameter) stainless-steel (5 microm) Perfectsil Target ODS-3 reversed phase column with a mobile phase consisting of ammonium dihydrogen phosphate buffer (0.05 mol x L(-1), pH 5.8) and methanol (50:50, v/v), running at a flow rate of 1.5 ml x min(-1). The absorbance of the fluent was monitored at 254 nm. The developed method resulted in totally symmetrical peaks. It has been applied to assess the pharmacokinetics of oxazepam. Also the bioequivalence of two different oxazepam preparations following oral administration in healthy volunteers was assessed by this method.

An Energy-Efficient Target-Tracking Strategy for Mobile Sensor Networks.

In this paper, an energy-efficient strategy is proposed for tracking a moving target in an environment with obstacles, using a network of mobile sensors. Typically, the most dominant sources of energy consumption in a mobile sensor network are sensing, communication, and movement. The proposed algorithm first divides the field into a grid of sufficiently small cells. The grid is then represented by a graph whose edges are properly weighted to reflect the energy consumption of sensors. The proposed technique searches for near-optimal locations for the sensors in different time instants to route information from the target to destination, using a shortest path algorithm. Simulations confirm the efficacy of the proposed algorithm.

Optimized determination of lorazepam in human serum by extraction and high-performance liquid chromatographic analysis.

The present research was designated to evaluate a rapid and sensitive method for determining low concentrations of the highly active drug lorazepam in serum. Isolation of the drug from biological fluid after addition of nordazepam as the internal standard was achieved using a simple liquid-liquid extraction with dichloromethane and the extracted compounds were quantified by high-performance liquid chromatography. Chromatographic separation on a reversed phase column containing a stationary phase with low silanol activity resulted in a perfectly symmetrical peak with a tailing factor of 1.0. The limit of quantitation in serum is 2.5 ng mL(-1) for both lorazepam and internal standard. The procedure is rapid and sensitive enough for determination of lorazepam in serum.