Green HPLC-DAD and HPTLC Methods for Quantitative Determination of Binary Mixture of Pregabalin and Amitriptyline Used for Neuropathic Pain Management.

First analytical methods were herein developed for determination of pregabalin (PGB) and amitriptyline (AMT) as an active binary mixture used for management of neuropathic pain whether in pure forms or in human biological fluids (plasma/urine). First method is green high-performance liquid chromatography-diode array detector (HPLC-DAD) after derivatization of PGB with ninhydrin (NIN) on a reversed-phase C18 column using a mobile phase consisting of ethanol:water (97:3%, v/v) pumped isocratically at 0.8 mL/min; AMT were scanned at 215 nm, whereas PGB-NIN was scanned at 580 nm. Second method is High-performance thin-layer chromatography (HPTLC), where PGB and AMT were separated on silica gel HPTLC F254 plates, using ethanol:ethyl acetate:acetone:ammonia solution (8:2:1:0.05, by volume) as a developing system. AMT peaks were scanned at 220 nm, whereas PGB peaks were visualized by spraying 3% (w/v) ethanolic NIN solution and scanning at 550 nm. Linear calibration curves were obtained for human plasma and urine spiked with PGB and AMT over the ranges of 5-100 µg/mL and 0.2-2.5 µg/band for PGB, and 1-100 µg/mL and 0.1-2.0 µg/band for AMT for HPLC-DAD and HPTLC methods, respectively. The suggested methods were validated according to Food and Drug Administration guidelines for bioanalytical methods validation and they can be applied for routine therapeutic drug monitoring for the concerned drugs.

Polyoxomolybdate368 /polyaniline nanocomposite as a novel fiber for solid-phase microextraction of antidepressant drugs in biological samples.

A novel solid-phase microextraction fiber was synthesized by coating a stainless steel wire with polyoxomolybdate368 /polyaniline as a sorbent aimed at extraction of amitriptyline, nortriptyline, and doxepin as antidepressant drugs from urine and blood samples. The polyoxomolybdate368 /polyaniline composite coating was applied using electropolymerization process under constant potential. This composition leads to enhanced extraction efficiency of the fiber. Scanning electron microscopy images show that huge three-dimensional structures of polyoxomolybdate368 in composite induced more non-smooth and porous fiber. In order to optimize of the extraction process, a series of variables including concentration of the composite materials, coating thickness, pH, extraction time, salt addition, and stirring rate was investigated and optimum conditions were determined. Analysis of surface morphology and chemical composition was performed. High-performance liquid chromatography was used for separation and evaluation of mentioned antidepressant drugs from the matrixes. The experiments indicated a detection limits of <0.2 ng/L and a linear dynamic range of 0.3-100 ng/L (R2  > 0.994). The relative recovery values were found to be in the range of 92-98%. It was concluded that the purposed fiber is highly efficient in analyzing traces of antidepressant drugs in urine and blood.

A green and low-cost method employing switchable hydrophilicity solvent for the simultaneous determination of antidepressants in human urine by gas chromatography - mass spectrometry detection.

In this study, the use of switchable hydrophilicity solvent with a simple and low-cost lab-made device for the extraction procedure in homogeneous liquid-liquid microextraction is proposed for the first time in the determination of antidepressants in human urine. The antidepressants studied consisted of fluoxetine, amitriptyline, nortriptyline, imipramine, desipramine and sertraline. The optimization of the main parameters that can influence on the extraction efficiency was performed through multivariate approaches. The analytes were separated and identified by gas chromatography coupled to mass spectrometry (GC-MS). The optimal extraction conditions consisted of using N,N-dimethylcyclohexylamine (DMCHA) as the switchable hydrophilicity solvent (SHS), 500 µL of urine sample previously diluted with ultrapure water at 1:1 ratio (v/v), 200 µL of a mixture of SHS:HCl 6 mol L-1 (1:1 v/v), 600 µL of NaOH 10 mol L-1 and 3 min of extraction time. A volume of 40 µL of diphenylamine at concentration of 500 µg L-1 (20 ng) was used as internal standard. The method developed was in-house validated, providing coefficients of determination higher than 0.995 for all analytes, limits of detection (LOD) from 0.02 to 0.88 µg L-1, limits of quantification (LOQ) from 0.05 to 2.92 µg L-1, relative recoveries of 68 to 102%, intra-day precision from 0.5 to 15.9%, inter-day precision from 4.2 to 19.3%, selectivity and robustness. The method proposed was successfully applied in five human urine samples from a Toxicological Information Center located in Porto Alegre (Brazil). The results demonstrated that the µP-SHS-HLLME approach is highly cost-effective, rapid, simple and environmentally-friendly with satisfactory analytical performance.

Supramolecular microextraction combined with paper spray ionization mass spectrometry for sensitive determination of tricyclic antidepressants in urine.

This work describes a novel methodology to analyze four tricyclic antidepressants (amitriptyline, doxepin, imipramine and, nortriptyline) in urine samples by combining supramolecular microextraction and paper spray ionization mass spectrometry (PS-MS). The proposed method uses a supramolecular solvent in which reverse micelles of 1-decanol are dispersed in tetrahydrofuran (THF)/water. The extraction of the tricyclic antidepressants at pH 9.0 requires a sample volume of 10.0 mL, short extraction time (1.0 min of extraction and 5 min of centrifugation), low amounts of organic solvent (50 µL of 1-decanol and 200 µL of THF), and provides high preconcentration factors: 96.9 to amitriptyline, 93.6 to doxepin, 71.3 to imipramine, and 146.9 to nortriptyline. The quantification by PS-MS is fast and straightforward because chromatographic separation is not required and all analytes were determined simultaneously. The limits of detection (LOD), quantification (LOQ), and the precision (RSD, %) of the developed method ranged between 5.2 and 8.6 µg L-1, 17.4-28.7 µg L-1 and 1.3-12.9%, respectively. Urine samples of five individuals (three males and two females) were used for accuracy evaluation. The accuracy obtained in these spiked urine samples at µg L-1 levels varied from 95.3 to 112.0%. The method also provided clean mass spectra with a high signal-to-noise ratio, which demonstrates the analytical appeal combination of supramolecular microextraction with determination by paper spray mass spectrometry.

Storage of urine specimens in point of care (POC) urine drug testing cups reduces concentrations of many drugs.

BACKGROUND: Many clinical toxicology laboratories receive urine specimens in urine cups that contain point of care (POC) drug testing strips. We conducted this study to evaluate the effect on the stability of commonly measured drugs in the clinical toxicology laboratory when urine is exposed to POC urine drug testing cups. METHODS: Drug free urine was spiked with 85 drugs that were measured by a validated liquid chromatography mass spectrometry (LCMS) method after exposure to POC urine drug testing cups at ambient and 2-6 °C temperatures. Alterations ≥20% were defined as significant changes in the drugs concentration. RESULTS: Concentrations of amitriptyline, cyclobenzaprine, fentanyl, fluoxetine, flunitrazepam, nortriptyline, paroxetine, and sertraline were significantly reduced when urine specimens were stored inside POC urine drug testing cups for 24 h at ambient temperature. Storage of urine in urine chemistry dipsticks reduced the concentration of several drugs. When spiked urine was exposed to an increasing number of POC urine drug testing strips, the concentrations of some drugs were reduced in a dose-dependent manner. The drugs that were absorbed by POC urine drug testing strips were partially back extracted from the strips. CONCLUSION: Exposure of urine specimens to POC urine drug testing strips reduces the concentration of several drugs measured by LCMS method.

Green analytical chromatographic assay method for quantitation of cyclobenzaprine in tablets, spiked human urine and in-vitro dissolution test.

Cyclobenzaprine hydrochloride, a skeletal muscle relaxant has been determined using an ecofriendly micellar HPLC method in its pure form and tablets. The chromatographic determination was performed using C8 monolithic column (100mm×4.6mm i.d., 5µm particle size) and micellar eluent which was composed of sodium dodecyl sulfate (0.15M), n-propanol (15%), 0.02M orthophosphoric acid (pH 4.5) and 0.3% triethylamine using UV detection of effluent was set at 225nm. The calibration plot showed good linearity over concentration range from 2-40µg/mL. The assay results were statistically validated for linearity, accuracy, precision and specificity according to ICH guidelines. Additionally, regarding USP guidelines, the uniformity of tablets content and in-vitro dissolution test of the tablets was tested using the proposed method. Simple and rapid applicability of the developed method allowed determination of the drug in its pure and tablet dosage forms. Moreover, the major advantage of micellar HPLC technique is to determine the drug in biological fluids without prior extraction steps. Depending on this, the estimation of cyclobenzaprine in spiked human urine was so simple without traditional tedious procedures. The proposed method offers the advantages of sensitivity and simplicity in addition to short analysis time which didn't exceed 6 minutes.

High-throughput paper spray mass spectrometry via induced voltage.

RATIONALE: Paper spray (PS) has been developed as a method of choice for point-of-care analysis in many real cases, where its applications can be further expanded with delicate high-throughput design. To achieve this goal, we developed a new PS regime, with the assembly of an induced high voltage into the ion source. Compared with regular DC high voltage, the newly developed setup is capable of high-throughput, simple configuration and rapid switching between individual papers without complicated electric/mechanic design. METHODS: A device of high-throughput induced PS (IPS) was designed by using a two-dimensional (2D) rotating platform equipped with a circular glass plate. The paper substrate was placed on the circular glass plate and separated from the electrode. The method avoids physical contact between the electrode and the sample. Charged droplets were generated at the paper tip once an induced high voltage was applied to a wet paper. RESULTS: A relatively rapid analytical speed of 2.6 s per sample was achieved via IPS-MS. Rapid quantification of amitriptyline (AMT) in complicated matrices was obtained within 1 min using an isotope internal standard method. Limits of detection for AMt in urine, FBS and blood were calculated to be 1.04, 0.84 and 1.33 ng/mL, respectively. In addition, high-throughput IPS-MS can be used for chemical reaction monitoring. CONCLUSIONS: We have demonstrated the versatility of high-throughput IPS-MS in ambient ionization, which successfully simplified the experimental installation and facilitated the experimental operation. Therefore, we believe that high-throughput IPS-MS analysis will be widely used for discovering drugs and screening reactions, and the present design has the potential for applications in paper chip-MS analysis.

Carbon Nanohorn Suprastructures on a Paper Support as a Sorptive Phase.

This article describes a method for the modification of paper with single-wall carbon nanohorns (SWCNHs) to form stable suprastructures. The SWCNHs form stable dahlia-like aggregates in solution that are then self-assembled into superior structures if the solvent is evaporated. Dipping paper sections into a dispersion of SWCNHs leads to the formation of a thin film that can be used for microextraction purposes. The coated paper can be easily handled with a simple pipette tip, paving the way for disposable extraction units. As a proof of concept, the extraction of antidepressants from urine and their determination by direct infusion mass spectrometry is studied. Limits of detection (LODs) were 10 ng/L for desipramine, amitriptyline, and mianserin, while the precision, expressed as a relative standard deviation, was 7.2%, 7.3%, and 9.8%, respectively.

Magnetic micro-solid-phase extraction based on magnetite-MCM-41 with gas chromatography-mass spectrometry for the determination of antidepressant drugs in biological fluids.

A new facile magnetic micro-solid-phase extraction coupled to gas chromatography and mass spectrometry detection was developed for the extraction and determination of selected antidepressant drugs in biological fluids using magnetite-MCM-41 as adsorbent. The synthesized sorbent was characterized by several spectroscopic techniques. The maximum extraction efficiency for extraction of 500 µg/L antidepressant drugs from aqueous solution was obtained with 15 mg of magnetite-MCM-41 at pH 12. The analyte was desorbed using 100 µL of acetonitrile prior to gas chromatography determination. This method was rapid in which the adsorption procedure was completed in 60 s. Under the optimized conditions using 15 mL of antidepressant drugs sample, the calibration curve showed good linearity in the range of 0.05-500 µg/L (r2  = 0.996-0.999). Good limits of detection (0.008-0.010 µg/L) were obtained for the analytes with good relative standard deviations of <8.0% (n = 5) for the determination of 0.1, 5.0, and 500.0 µg/L of antidepressant drugs. This method was successfully applied to the determination of amitriptyline and chlorpromazine in plasma and urine samples. The recoveries of spiked plasma and urine samples were in the range of 86.1-115.4%. Results indicate that magnetite micro-solid-phase extraction with gas chromatography and mass spectrometry is a convenient, fast, and economical method for the extraction and determination of amitriptyline and chlorpromazine in biological samples.

Urinary Concentrations of Topically Administered Pain Medications.

A common treatment for chronic pain is prescription of analgesics, but their long-term use entails risk of morbidity, addiction and misuse. One way to reduce the risk of abuse is prescribing of analgesics in a topical form. Physicians are urged to perform urine drug testing to ensure that patients are compliant with their medication regimens. However, there is little data on the efficiency of transdermal delivery for many analgesic drugs, and no data on expected urine drug levels. This study includes data from over 29,000 specimens tested for gabapentin, ketamine, cyclobenzaprine or amitriptyline used orally or topically. Gabapentin and amitriptyline concentrations were more likely to be below the limits of detection (25-40 ng/mL) in the urine of patients using them topically as compared with patients using them orally. Levels in gabapentin-positive topical specimens were much lower than in gabapentin-positive oral specimens (261 ng/mL vs >10,000 ng/mL). In contrast, ketamine and cyclobenzaprine were more readily detectable in the urine of topical users. Ketamine topical specimens were positive 12% more often than oral specimens, and mean topical specimen levels were 68-100% those of oral specimens. Cyclobenzaprine specimens were equally likely to be positive whether the dose was oral or topical, although mean levels after topical dosing were approximately 13-21% those after oral dosing. These findings are consistent with the reported percutaneous absorption efficiencies of gabapentin and ketamine, and are likely to be related to the absorption efficiencies of cyclobenzaprine and amitriptyline.

Polythiophene/graphene oxide nanostructured electrodeposited coating for on-line electrochemically controlled in-tube solid-phase microextraction.

In this work, a novel polythiophene/graphene oxide (PTh/GO) nanostructured coating was introduced for on-line electrochemically-controlled in-tube solid phase microextraction of amitriptyline (AMI) and doxepin (DOX) as antidepressant drugs. The PTh/GO coating was prepared on the inner surface of a stainless steel tube by a facile in-situ electro-deposition method and it was used as a working electrode for electrochemically control in-tube solid phase microextraction. In the PTh/GO coating, GO acts as an anion dopant and sorbent. The PTh/GO coating, compared to PTh and GO coatings, exhibited enhanced long lifetime, good mechanical stability and a large specific surface area. Regarding the in-tube SPME, some important factors such as the extraction and desorption voltage, extraction and desorption times and flow rates of the sample solution and eluent, which could affect the extraction and separation efficiency of the analytes, were optimized. Total analysis time of this method including the online extraction and desorption time was about 21min for each sample. AMI and DOX were extracted, separated and determined with limits of detection as small as 0.3µgL-1 and 0.5µgL-1, respectively. This method showed good linearity in the range of 0.7-200µgL-1, 2.3-200µgL-1 and 2.9-200µgL-1 for AMI, and in the range 0.9-200µgL-1, 2.5-200µgL-1 and 3.0-200µgL-1 for DOX in water, urine and plasma samples, respectively; the coefficients of determination were also equal to or higher than 0.9976. The inter- and intra-assay precisions (RSD%, n=3) were in the range of 2.8-3.4% and 2.9-3.9% at the three concentration levels of 5, 25 and 50µgL-1, respectively. Finally, under the optimal conditions, the method was applied for the analysis of the drugs in human urine and plasma pretreated samples and good results were obtained.

Variations in enzymatic hydrolysis efficiencies for amitriptyline and cyclobenzaprine in urine.

A collaborative study was conducted to investigate discrepancies in recoveries of two commonly prescribed compounds, amitriptyline and cyclobenzaprine, in patient urine samples when hydrolyzed with different enzymes from different sources. A 2- to 10-fold increase in analyte recoveries was seen for patient samples hydrolyzed using a recombinant ß-glucuronidase (IMCSzyme™) over samples hydrolyzed with ß-glucuronidase from Haliotis rufescens We report outcomes from four commercially available ß-glucuronidase enzymes (IMCSzyme™, Patella vulgata, Helix pomatia and H. rufescens) on patient samples that tested positive for amitriptyline and cyclobenzaprine. Our results confirm reduced hydrolysis of glucuronides by ß-glucuronidases isolated from mollusks, but near complete conversion when using the recombinant enzyme. Our premise is that systematic differences in hydrolysis efficiencies due to varying substrate affinity among enzyme subtypes potentially impacts accuracy and reliability of measurements.

Metabolism and bioactivation of the tricyclic antidepressant amitriptyline in human liver microsomes and human urine.

AIM: Amitriptyline is a widely used tricyclic antidepressant, but the metabolic studies were conducted almost 20 years ago using high-performance liquid chromatography coupled with ultraviolet detector or radiolabeled methods. RESULTS: First, multiple ion monitoring (MIM)- enhanced product ion (EPI) scan was used to obtain the diagnostic ions or neutral losses in human liver microsome incubations with amitriptyline. Subsequently, predicted multiple reaction monitoring (MRM)-EPI scan was used to identify the metabolites in human urine with the diagnostic ions or neutral losses. Finally, product ion filtering and neutral loss filtering were used as the data mining tools to screen metabolites. Consequently, a total of 28 metabolites were identified in human urine after an oral administration using LC-MS/MS. CONCLUSION: An integrated workflow using LC-MS/MS was developed to comprehensively profile the metabolites of amitriptyline in human urine, in which five N-acetyl-l-cysteine conjugates were characterized as tentative biomarkers for idiosyncratic toxicity.

Dynamic electromembrane extraction: Automated movement of donor and acceptor phases to improve extraction efficiency.

In the present research, dynamic electromembrane extraction (DEME) was introduced for the first time for extraction and determination of ionizable species from different biological matrices. The setup proposed for DEME provides an efficient, stable, and reproducible method to increase extraction efficiency. This setup consists of a piece of hollow fiber mounted inside a glass flow cell by means of two plastics connector tubes. In this dynamic system, an organic solvent is impregnated into the pores of hollow fiber as supported liquid membrane (SLM); an aqueous acceptor solution is repeatedly pumped into the lumen of hollow fiber by a syringe pump whereas a peristaltic pump is used to move sample solution around the mounted hollow fiber into the flow cell. Two platinum electrodes connected to a power supply are used during extractions which are located into the lumen of the hollow fiber and glass flow cell, respectively. The method was applied for extraction of amitriptyline (AMI) and nortriptyline (NOR) as model analytes from biological fluids. Effective parameters on DEME of the model analytes were investigated and optimized. Under optimized conditions, the calibration curves were linear in the range of 2.0-100µgL(-1) with coefficient of determination (r(2)) more than 0.9902 for both of the analytes. The relative standard deviations (RSD %) were less than 8.4% based on four replicate measurements. LODs less than 1.0µgL(-1) were obtained for both AMI and NOR. The preconcentration factors higher than 83-fold were obtained for the extraction of AMI and NOR in various biological samples.

[The determination of amitriptyline and its metabolite, nortriptyline, in the biological objects of the corpse by the high-performance liquid chromatography technique].

Tricyclic antidepressants are among the preparations that most frequently cause intoxication in adults and children; moreover, poisoning with these substances not infrequently has a fatal outcome. Medications belonging to this group, such as amitriptyline, are extensively used to manage manifestations of depression, anxiety, migraine, neuropathic pain, and hyperactivity syndrome. Amitriptyline overdosage causes non-specific symptoms of intoxication, and its clinical picture does not allow to identify the nature of a psychotropic xenobiotic. Of primary importance in connection with this is to establish the cause of intoxication or death by the clinical toxicological and forensic medical methods based on the results of the fast identification and quantitation of amitriptyline in biological materials including blood, urine, hepatic tissues, etc. The authors describe the method for the determination of amitriptyline and its principal physiological metabolite nortriptyline in biological objects with the help of high performance liquid chromatography (HPLC).

Repetitive injection field-amplified sample stacking for cationic compounds determination.

The development of a field-amplified sample stacking technique is presented. Sensitivity enhancement in this technique was obtained by repetitive injections of a sample followed by steps of sample matrix removal through the application of counter-pressure. Under optimized conditions the background electrolyte (BGE) was composed of 80 mM H3PO4 while the sample matrix contained 0.5mM H3PO4 and 30% (v/v) methanol. The elaborated method enabled a 4-fold effective injection of the sample (53 s, 0.5 psi). Each injection was followed by a focusing step during which the application of a voltage (2 kV) and counter-pressure (-1 psi) was performed for 0.65 min. The method was developed for the determination of six psychiatric drugs (opipramol, hydroxyzine, promazine, amitriptyline, fluoxetine, and thioridazine). The elaborated method was applied for analysis of human urine samples after a simple liquid-liquid extraction procedure. The detection limits obtained were in the range of 2.23-6.21 ng/mL.

Tricyclic antidepressants: is your patient taking them? Observations on adherence and unreported use using prescriber-reported medication lists and urine drug testing.

OBJECTIVE: Tricyclic antidepressants (TCAs) are first-line treatment for neuropathic pain. Despite widespread use, many health care providers do not know which patients are currently taking TCAs. The objective of this retrospective data analysis was to determine adherence rates to amitriptyline, nortriptyline, or imipramine. The rate at which patients used TCAs (confirmed by presence of TCA in the urine) but did not inform their health care provider is also reported (non-informed prescriber rate). Finally, the effects of age, sex, and number of prescriptions on adherence and non-informed prescriber rates were assessed. METHODS: Urinary excretion data were obtained from 55,296 patients with pain and were analyzed using liquid chromatography tandem mass spectrometry in a multiplex assay which included amitriptyline, nortriptyline, and imipramine. RESULTS: The adherence rate was 66% (1,407/2,137); the rate of non-informed prescribers was 3% (1,547/55,296) among the general population, and 52% (1,547/2,954) when only TCA users were considered. While adherence was higher among older and female subjects, the number of other medications did not affect adherence rate. CONCLUSIONS: This analysis reveals that many prescribers are not informed when patients start and stop using TCAs.

Nepem-211 ion exchange conductive membrane immobilized tris(2,2´-bipyridyl) ruthenium(II) electrogenerated chemiluminescence flow sensor for high-performance liquid chromatography and its application.

We developed a sensitive and robust electrogenerated chemiluminescence (ECL) flow sensor based on Ru(bpy)3(2+) immobilized with a Nepem-211 perfluorinated ion exchange conductance membrane, which has robustness and stability under a wide range of chemical and physical conditions, good electrical conductivity, isotropy and a high exchange capacity for immobilization of Ru(bpy)3(2+). The flow sensor has been used as a post-column detector in high-performance liquid chromatography for determination of erythromycin and clarithromycin in honey and pork, and tricyclic antidepressant drugs in human urine. Under optimal conditions, the linear ranges were 0.03-26 ng/µL and 0.01-1 ng/µL for macrolides and tricyclic antidepressant drugs, respectively. The detection limits were 0.02, 0.01, 0.01, 0.06 and 0.003 ng/µL for erythromycin, clarithromycin, doxepin, amitriptyline and clomipramine, respectively. There is no post-column reagent addition. In addition to the conservation expensive reagents, the experimental setup was simplified. The flow sensor was used for 2 years with high sensitivity and stability.

Electromembrane surrounded solid phase microextraction: a novel approach for efficient extraction from complicated matrices.

In the present work, electromembrane surrounded solid phase microextraction (EM-SPME) is introduced for the first time. The organic liquid membrane, which consists of 2-nitrophenyl octyl ether (NPOE), was immobilized in the pores of a hollow fiber (HF) and the basic analytes migrated in an electrical field from aqueous sample solution through the liquid membrane and into aqueous acceptor phase and then they were adsorbed on the solid sorbent, which acts as the cathode. Effective parameters such as composition of organic liquid membrane, pH of donor and acceptor phases, applied voltage and extraction time were optimized for extraction of amitriptyline (AMI) and doxepin (DOX) as model analytes and figures of merit of the method were investigated in pure water, human plasma, and urine samples. To extract the model analytes from 24 mL neutral sample solution across organic liquid membrane and into aqueous acceptor phase, 120 V electrical potential was applied for 20 min and finally the drugs were adsorbed on a carbonaceous cathode. Regardless of high sample cleanup, which make the proposed method suitable for the analysis of drugs from complicated matrices, extraction efficiencies in the range of 3.1-11.5% and good detection limits (less than 5 ngmL(-1)) with admissible repeatability and reproducibility (intra- and inter-assay precisions ranged between 4.0-8.5% and 7.5-12.2%, respectively) were obtained from different extraction media. Linearity of the method was studied in the range of 2.0-500.0 ngmL(-1) and 5.0-500.0 ngmL(-1) for AMI and DOX, respectively and coefficient of determination higher than 0.9947 were achieved. Finally, the proposed method was applied for the analysis of AMI and DOX in real samples.

Significant toxicity in a young female after low-dose tricyclic antidepressant ingestion.

BACKGROUND: Tricyclic antidepressant (TCA) ingestions are a relatively common pediatric ingestion, with significant potential for both cardiac and neurological toxicity. Previous studies on pediatric TCA ingestions have found the threshold of toxicity to be 5 mg/kg. CASE: We report a case of an 8-year-old girl who presented to the emergency department with depressed mental status and seizure-like movements. An extensive workup was pursued to evaluate the cause of her mental status, which only revealed a positive urine toxicology screen for TCA. Quantified serum levels of amitriptyline were 121 ng/mL (therapeutic range, 50-300 ng/mL) and nortriptyline were 79 ng/mL (therapeutic range 70-170 ng/mL), 18 hours after onset of symptoms. Subsequent history obtained after her mental status returned to normal revealed that she had ingested amitriptyline at a dose of 0.8 mg/kg. CONCLUSIONS: Tricyclic antidepressant ingestion has a high potential for toxicity in pediatric patients. This case suggests, contrary to previous literature, that toxicity may occur even with small doses.