Analysis of new psychoactive substances in human urine by ultra-high performance supercritical fluid and liquid chromatography: Validation and comparison.

New psychoactive substances represent serious social and health problem as tens of new compounds are detected in Europe annually. They often show structural proximity or even isomerism, which complicates their analysis. Two methods based on ultra high performance supercritical fluid chromatography and ultra high performance liquid chromatography with mass spectrometric detection were validated and compared. A simple dilute-filter-and-shoot protocol utilizing propan-2-ol or methanol for supercritical fluid or liquid chromatography, respectively, was proposed to detect and quantify 15 cathinones and phenethylamines in human urine. Both methods offered fast separation (<3 min) and short total analysis time. Precision was well <15% with a few exceptions in liquid chromatography. Limits of detection in urine ranged from 0.01 to 2.3 ng/mL, except for cathinone (5 ng/mL) in supercritical fluid chromatography. Nevertheless, this technique distinguished all analytes including four pairs of isomers, while liquid chromatography was unable to resolve fluoromethcathinone regioisomers. Concerning matrix effects and recoveries, supercritical fluid chromatography produced more uniform results for different compounds and at different concentration levels. This work demonstrates the performance and reliability of supercritical fluid chromatography and corroborates its applicability as an alternative tool for analysis of new psychoactive substances in biological matrixes.

Detection of Volatile Organic Compounds in a Drop of Urine by Ultrasonic Nebulization Extraction Proton Transfer Reaction Mass Spectrometry.

Detection of volatile organic compounds (VOCs) in human urine has potential application value in screening for disease and toxin exposure. However, the current technologies are too slow to detect the concentration of VOCs in fresh urine. In this study, we developed a novel ultrasonic nebulization extraction proton transfer reaction mass spectrometry (UNE-PTR-MS) technology. The urinary VOCs can be rapidly extracted to gaseous VOCs using the UNE system and then delivered using a carrier gas to the PTR-MS instrument for rapid detection. The carrier gas flow and sample size were optimized to 100 mL/min and 100 µL, respectively. The limits of detection (LODs) and response time of the UNE-PTR-MS were evaluated by detecting three VOCs that are common in human urine: methanol, acetaldehyde, and acetone. The LODs determined for methanol (4.47 µg/L), acetaldehyde (1.98 µg/L), and acetone (3.47 µg/L) are 2-3 orders of magnitude lower than the mean concentrations of that in healthy human urine. The response time of the UNE-PTR-MS is 34 s and only 0.66 mL of urine is required for a full scan. The repeatability of this UNE-PTR-MS was evaluated, and the relative standard deviations of 5 independent determinations were between 4.62% and 5.21%. Lastly, the UNE-PTR-MS was applied for detection of methanol, acetaldehyde, and acetone in real human urine to test matrix effects, yielding relative recoveries of between 88.39% and 94.54%. These results indicate the UNE-PTR-MS can be used for the rapid detection of VOCs in a drop of urine and has practical potential for diagnosing disease or toxin exposure.

Urine methanol concentration and alcohol hangover severity.

BACKGROUND: Congeners are substances, other than ethanol, that are produced during fermentation. Previous research found that the consumption of congener-rich drinks contributes to the severity of alcohol hangover. Methanol is such a congener that has been related to alcohol hangover. Therefore, the aim of this study was to examine the relationship between urine methanol concentration and alcohol hangover severity. METHODS: N = 36 healthy social drinkers (22 females, 14 males), aged 18-30 years old, participated in a naturalistic study, comprising a hangover day and a control day (no alcohol consumed the previous day). N = 18 of them had regular hangovers (the hangover group), while the other N = 18 claimed to be hangover-immune (hangover-immune group). Overall hangover severity was assessed, and that of 23 individual hangover symptoms. Urine methanol concentrations on the hangover and control days were compared, and correlated to hangover (symptom) severity. RESULTS: Urine methanol concentration was significantly higher on hangover days compared to control days (p = 0.0001). No significant differences in urine methanol concentration were found between the hangover group and hangover-immune group. However, urine methanol concentration did not significantly correlate with overall hangover severity (r = -0.011, p = 0.948), nor with any of the individual hangover symptoms. These findings were observed also when analyzing the data separately for the hangover-immune group. In the hangover group, a significant correlation with urine methanol concentration was found only with vomiting (r = 0.489, p = 0.037). CONCLUSION: No significant correlation was observed between urine methanol concentration and hangover severity, nor with individual core hangover symptoms.

Improved detection of alcohol consumption using the novel marker phosphatidylethanol in the transplant setting: results of a prospective study.

Phosphatidylethanol (PEth) is a new, highly specific alcohol marker. The aim of this study was to assess its diagnostic value in the liver transplant setting. In 51 pre- and 61 post-transplant patients with underlying alcoholic liver disease PEth, ethanol, methanol, carbohydrate-deficient transferrin (CDT), and ethyl glucuronide in urine (uEtG) and hair (hEtG) were tested and compared with patients' questionnaire reports. Twenty-eight (25%) patients tested positive for at least one alcohol marker. PEth alone revealed alcohol consumption in 18% of patients. With respect to detection of alcohol intake in the preceding week, PEth showed a 100% sensitivity. PEth testing was more sensitive than the determination of ethanol, methanol, CDT or uEtG alone [sensitivity 25% (confidence interval (CI) 95%, 7-52%), 25% (7-52%), 21% (6-45%) and 71% (41-91%), respectively], or ethanol, methanol and uEtG taken in combination with 73% (45-92%). Specificity of all markers was 92% or higher. Additional testing of hEtG revealed alcohol consumption in seven patients, not being positive for any other marker. Phosphatidylethanol was a highly specific and sensitive marker for detection of recent alcohol consumption in pre- and post-transplant patients. The additional determination of hEtG was useful in disclosing alcohol consumption 3-6 months retrospectively.

Simultaneous Determination of Methanol, Ethanol and Formic Acid in Serum and Urine by Headspace GC-FID.

A simple, cost-effective headspace gas chromatography (GC) method coupled with GC with flame ionization detection for simultaneous determination of methanol, ethanol and formic acid was developed and validated for clinical and toxicological purposes. Formic acid was derivatized with an excess of isopropanol under acidic conditions to its volatile isopropyl ester while methanol and ethanol remained unchanged. The entire sample preparation procedure is complete within 6 min. The design of the experiment (the face-centered central composite design) was used for finding the optimal conditions for derivatization, headspace sampling and chromatographic separation. The calibration dependences of the method were quadratic in the range from 50 to 5,000 mg/L, with adequate accuracy (89.0-114.4%) and precision (<12%) in the serum. The new method was successfully used for determination of selected analytes in serum samples of intoxicated patients from among those affected by massive methanol poisonings in the Czech Republic in 2012.

Human metabolism of Δ3-carene and renal elimination of Δ3-caren-10-carboxylic acid (chaminic acid) after oral administration.

We studied the human in vivo metabolism of Δ(3)-carene (CRN), a natural monoterpene which commonly occurs in the human environment. Four healthy human volunteers were orally exposed to a single dose of 10 mg CRN. Each volunteer gave one urine sample before administration and subsequently collected each urine sample within 24 h after administration. The concentration of the proposed CRN metabolites Δ(3)-caren-10-ol (CRN-10-OH), Δ(3)-caren-10-carboxylic acid (chaminic acid, CRN-10-COOH), and Δ(3)-caren-3,4-diol (CRN-3,4-OH) were determined using a very specific and sensitive GC-MS/MS procedure. Other CRN metabolites were investigated using GC-PCI-MS Q1 scan analyses. CRN-10-COOH was detected in each urine sample with maximum concentration (113.0-1,172.9 µg L(-1)) 2-3 h after administration, whereas CRN-10-OH and CRN-3,4-OH were not detected in any of the samples. The renal excretion kinetics of CRN-10-COOH showed an elimination half-life of about 3 h. The cumulative excretion of CRN-10-COOH within 24 h after exposure correlated with about 2 % of the applied dose. The GC-PCI-MS Q1 scan analysis indicated several additional human CRN metabolites; thereof, six spectra enabled the prediction of the corresponding chemical structure. The results of the study indicate that CRN-10-COOH is a relevant product of the human in vivo metabolism of CRN. The oxidation of its allylic methyl group proceeds until the acidic structure without interruption. Thus, the generation of the alcoholic intermediate appeared to be the rate-determining step of this metabolic route. Nevertheless, the proportion of CRN-10-COOH in the CRN metabolism is low, and other oxidative metabolites are likely. This hypothesis was confirmed by the discovery of additional human CRN metabolites, whose predicted chemical structures fit in with further oxidative products of CRN metabolism.

A singular case of survival after acute methanol poisoning: toxicological and neuroimaging findings.

Acute methanol poisoning is a relatively uncommon and dangerous form of intoxication. It generally occurs after suicidal or accidental events and can be potentially fatal if not diagnosed and treated promptly. Here reported is the case of a 52-year-old Romanian man who survived acute methanol intoxication. Therefore, it was possible to monitor the clinical evolution, the arterial blood gas assay and toxicological research of methanol in blood and urine, as well as the brain damage by computed tomography and magnetic resonance imaging during a period of 20 days after the intake.

Comparison of direct and indirect alcohol markers with PEth in blood and urine in alcohol dependent inpatients during detoxication.

The importance of direct and indirect alcohol markers to evaluate alcohol consumption in clinical and forensic settings is increasingly recognized. While some markers are used to prove abstinence from ethanol, other markers are suitable for detection of alcohol misuse. Phosphatidyl ethanol (PEth) is ranked among the latter. There is only little information about the correlation between PEth and other currently used markers (ethyl glucuronide, ethyl sulfate, carbohydrate deficient transferrin, gamma-glutamyl transpeptidase, and methanol) and about their decline during detoxification. To get more information, 18 alcohol-dependent patients in withdrawal therapy were monitored for these parameters in blood and urine for up to 19 days. There was no correlation between the different markers. PEth showed a rapid decrease at the beginning of the intervention, a slow decline after the first few days, and could still be detected after 19 days of abstinence from ethanol.

[Confirmed poisonings with ethylene glycol and methanol in south Poland in the years 2010-2012 based on results from toxicological laboratories in Kraków and Sosnowiec]. / Potwierdzone zatrucia glikolem etylenowym i alkoholem metylowym w Polsce poludniowej w latach 2010-2012 na podstawie wyników oznaczen laboratoriów toksykologicznych w Krakowie i Sosnowcu.

The purpose of the research was to present the number of ethylene glycol and methanol poisonings in south Poland in the years 2010-2012, based on data from toxicological laboratories in Kraków and Sosnowiec. Total numbers of positive determinations of the toxic alcohols were 380-ethylene glycol and 152-methanol. Most of the patients poisoned with the toxic alcohols were men (87.4%), the mean age of the patients was 48.1 years. Mean ethylene glycol concentration in samples from poisoned patients was 57.5 mg/dl in serum and 286.2 mg/dl in urine; mean blood methanol concentration was 1.4 g/l. Samples collected from poisoned patients treated on the area of whole voivodeship were determined in toxicology laboratories. According to information about orderers of ethylene glycol and methanol tests, positive results of the toxic alcohols were the most often in big cities and in cities, where department of toxicology were located (Kraków and Sosnowiec). In many cases patients were treated in hospitals in small cities, and samples collected from patients were transported to perform toxicological determination. The study shows, that intoxications with ethylene glycol and methanol are a big problem in Poland and the number of methanol poisonings markedly increased in the years 2010-2012.

Detection of autosomal dominant polycystic kidney disease by NMR spectroscopic fingerprinting of urine.

Autosomal dominant polycystic kidney disease (ADPKD) is a frequent cause of kidney failure; however, urinary biomarkers for the disease are lacking. In a step towards identifying such markers, we used multidimensional-multinuclear nuclear magnetic resonance (NMR) spectroscopy with support vector machine-based classification and analyzed urine specimens of 54 patients with ADPKD and slightly reduced estimated glomerular filtration rates. Within this cohort, 35 received medication for arterial hypertension and 19 did not. The results were compared with NMR profiles of 46 healthy volunteers, 10 ADPKD patients on hemodialysis with residual renal function, 16 kidney transplant patients, and 52 type 2 diabetic patients with chronic kidney disease. Based on the average of 51 out of 701 NMR features, we could reliably discriminate ADPKD patients with moderately advanced disease from ADPKD patients with end-stage renal disease, patients with chronic kidney disease of other etiologies, and healthy probands with an accuracy of >80%. Of the 35 patients with ADPKD receiving medication for hypertension, most showed increased excretion of proteins and also methanol. In contrast, elevated urinary methanol was not found in any of the control and other patient groups. Thus, we found that NMR fingerprinting of urine differentiates ADPKD from several other kidney diseases and individuals with normal kidney function. The diagnostic and prognostic potential of these profiles requires further evaluation.

The pharmacokinetics of methanol in the presence of ethanol: a case study.

BACKGROUND AND OBJECTIVE: Methanol is a toxic alcohol that can cause significant morbidity and mortality in overdose, while ethanol is a readily available and effective antidote. Little is known about the pharmacokinetics of methanol in the presence of ethanol and vice versa. This paper explores the influence of methanol and ethanol on the pharmacokinetics of each other along with the effect of continuous venovenous haemodiafiltration (CVVHD) on alcohol removal. METHODS: Multiple plasma, urine and dialysate samples were collected from a 42-year-old male who ingested 166 g of methanol. Methanol and ethanol concentrations in both plasma and urine were assayed and the concentration-time data were modelled using nonlinear mixed-effects modelling software NONMEM® VI. Simulations were performed using the final model parameters in MATLAB® software where a variety of initial doses and ethanol infusions were assessed. RESULTS: The final model included a competitive metabolic interaction between methanol and ethanol as well as first-order elimination due to renal, CVVHD and an additional non-renal non-CVVHD mechanism. Simulations from the model show a loading dose of 28.4 g/70 kg of ethanol results in a target plasma concentration of 1 g/L. Due to the competitive interaction between methanol and ethanol, higher amounts of methanol require lower maintenance doses of ethanol but for longer. CVVHD was shown to increase the dose rate of ethanol required but to decrease the duration of the maintenance phase. CONCLUSION: A detailed understanding of the pharmacokinetics of methanol and ethanol in the presence of each other is required to accurately determine the doses of ethanol required to treat different methanol poisonings.

Use of a holder-vacuum tube device to save on-site hands in preparing urine samples for head-space gas-chromatography, and its application to determine the time allowance for sample sealing.

To facilitate urine sample preparation prior to head-space gas-chromatographic (HS-GC) analysis. Urine samples containing one of the five solvents (acetone, methanol, methyl ethyl ketone, methyl isobutyl ketone and toluene) at the levels of biological exposure limits were aspirated into a vacuum tube via holder, a device commercially available for venous blood collection (the vacuum tube method). The urine sample, 5 ml, was quantitatively transferred to a 20-ml head-space vial prior to HS-GC analysis. The loaded tubes were stored at +4 ℃ in dark for up to 3 d. The vacuum tube method facilitated on-site procedures of urine sample preparation for HS-GC with no significant loss of solvents in the sample and no need of skilled hands, whereas on-site sample preparation time was significantly reduced. Furthermore, no loss of solvents was detected during the 3-d storage, irrespective of hydrophilic (acetone) or lipophilic solvent (toluene). In a pilot application, high performance of the vacuum tube method in sealing a sample in an air-tight space succeeded to confirm that no solvent will be lost when sealing is completed within 5 min after urine voiding, and that the allowance time is as long as 30 min in case of toluene in urine. The use of the holder-vacuum tube device not only saves hands for transfer of the sample to air-tight space, but facilitates sample storage prior to HS-GC analysis.

Elevated formic acid concentrations in putrefied post-mortem blood and urine samples.

Formic acid (FA) concentration was measured in post-mortem blood and urine samples as methyl formate using a headspace in-tube extraction gas-chromatography-mass-spectrometry method. A total of 113 cases were analyzed, each including a blood and urine sample fortified with 1% sodium fluoride. The cases were divided into three groups: regular (n=59), putrefied (n=30), and methanol-positive (n=22) cases. There was no evidence of ante-mortem methanol consumption in the regular and putrefied cases. In regular cases, the mean (and median) FA concentrations were 0.04 g/l (0.04 g/l) and 0.06 g/l (0.04 g/l) in blood and urine, respectively. In putrefied cases, the mean (and median) FA concentrations were substantially higher, 0.24 g/l (0.22 g/l) and 0.25 g/l (0.15 g/l) in blood and urine, respectively. In three putrefied cases, FA concentration in blood exceeded 0.5 g/l, a level associated with fatal methanol poisoning. Ten putrefied cases were reanalyzed after 3-4 months storage, and no significant changes in FA concentrations were seen. These observations suggest that FA was formed by putrefaction during the post-mortem period, not during sample storage when sodium fluoride was added as a preservative. In methanol-positive cases, the mean (and median) FA concentrations were 0.80 g/l (0.88 g/l) and 3.4 g/l (3.3 g/l) in blood and urine, respectively, and the concentrations ranged from 0.19 to 1.0 g/l in blood and from 1.7 to 5.6 g/l in urine. The mean (and median) methanol concentrations in methanol-positive cases were 3.0 g/l (3.0 g/l) and 4.4 g/l (4.7 g/l) in blood and in urine, respectively. The highest methanol concentrations were 6.0 g/l and 8.7 g/l in blood and urine, respectively. No ethyl alcohol was found in the methanol-positive blood samples. Poor correlation was shown between blood and urine concentrations of FA. Poor correlations were also shown, in both blood and urine, between methanol and FA concentrations.

Formation of methylselenol, dimethylselenide and dimethyldiselenide in in vitro metabolism models determined by headspace GC-MS.

The aim of this study was to identify the presence of MeSeH in metabolic reactions. An analytical method based on direct headspace GC-MS, eliminating loss of volatile species during sample pretreatment procedures, was developed for this purpose. The in vitro conversion of selenium compounds to the volatile species methylselenol, MeSeH, dimethyl selenide, DMeSe and dimethyl diselenide, DMeDSe was investigated. The analytical method was evaluated by means of standards of dimethyl diselenide, dimethyl selenide. The corresponding sulfides were found unsuitable as internal standards as they interacted with the selenides. The limit of detection was 0.25 µmol L(-1) (20 µg L(-1)) for the selenide as well as the diselenide. Formation of MeSeH was not observed in significant amount when selenomethionine was incubated with the enzyme l-methionine-γ-lyase; instead large amounts of DMeDSe were formed. In aqueous solution, methylseleninic acid, MeSeA reacted spontaneously with glutathione, GSH to form DMeDSe. In strongly reducing environments, however, MeSeH was also observed. When the formed MeSeH was trapped with iodoacetic acid, no DMeDSe was detected indicating that DMeDSe formation was due to spontaneous oxidation of MeSeH. These findings imply that DMeDSe may be a marker for the production of MeSeH in in vitro models. When MeSeA, Se-methylselenocysteine, Se-MeSeCys and SeMet were incubated with Jurkat cells, DMeDSe formation was only observed in the case of MeSeA. Trace amounts of DMeSe was observed in the vial with MeSeA as well as Se-MeSeCys. When DMeSe and DMeDSe were added to plasma, the sensitivity of only DMeDSe decreased significantly, implicating that DMeDSe underwent a reaction with plasma hindering the volatilization. This emphasizes that results from in vitro selenium metabolism studies may not be uncritically interpreted as consistent with the in vivo reality.

Measurement of free and bound alcohol metabolites and methanol in human biological samples--free and bound alcohol metabolites and methanol in acute alcohol administration.

There are almost no studies on the in vivo distribution kinetics of free and bound ethanol, alcohol metabolites (acetaldehyde and acetate) or the related substance, methanol, during alcohol oxidation. Thus, an acute alcohol administration experiment (alcohol consumption experiment) was carried out using volunteers (five healthy adult males; 2 flushers, 3 non-flushers), and distribution kinetics were investigated in biological samples (blood and urine). The levels of alcohol metabolites and methanol were measured as free compounds in blood samples and bound and free compounds in urine samples. The results showed an increase over time of free alcohol metabolites in both the flusher and non-flusher groups, followed by a subsequent decrease. In addition, free methanol increased over time. Both bound alcohol metabolites and bound methanol were found to increase over time. Based on these findings, levels of free and bound alcohol metabolites and methanol in the biological samples were found to increase relative to levels before consumption in both the flusher and non-flusher groups. This is thought to be due to the binding of alcohol metabolites and methanol to biological components and increases during ethanol oxidation. It was concluded that this is the mechanism by which ethanol, alcohol metabolites and methanol accumulate in the body as a result of chronic alcohol consumption, suggesting that it may be possible to use these compounds as markers of consumption by measuring these compounds in biological samples taken from alcohol abusers or alcoholics.

Use of acetaldehyde and methanol as markers of alcohol abuse and their measurement.

UNLABELLED: It is believed that ethanol metabolites (ethanol, acetaldehyde and acetate) are produced when alcohol is consumed in accumulation with the binding of biological components. Additionally, it has been reported that ethanol metabolites and methanol present in the blood and urine are bound to biological components in habitual alcohol drinkers, even when alcohol has not been consumed. Consequently, with the purpose of investigating the potential for effectively using ethanol metabolite and methanol as markers of alcohol abuse, acetaldehyde level was measured in blood hemoglobin samples, and ethanol, acetaldehyde and methanol levels were measured in urine samples in healthy adult males (volunteers: control group) and alcoholics that had not consumed alcohol. Simultaneously, investigations were carried out on the genetic analysis of ADH and ALDH enzymes that participate in ethanol metabolism. Acetaldehyde levels were found to be significantly higher in alcoholics than in the volunteers for the period of 2 to 3 months after admission. In urine samples, acetaldehyde level (bound) was significantly higher in the period of 2 to 3 months after admission, and methanol level (free and bound) was significantly higher within a period of 1 month after admission. A correlation between alcoholics and genotype was found with regard to the distribution of ADH2 and ALDH2 genotypes ( VOLUNTEERS: ADH2 2-2 type, 81%; ALDH2 1-1 type, 61.9%; Alcoholics: ADH2 2-2 type, 39.6%; ALDH2 1-1 type, 84.9%). Based on these results, alcoholism or alcohol abuse might be predicted by concentration of acetaldehyde as well as methanol during abstinence. It also might be used as markers of alcohol abuse.

Micellar electrokinetic chromatographic screening of letrozole and its metabolite in human urine: validation and robustness/ruggedness evaluation.

A simple, rapid, and sensitive method has been proposed and validated to directly quantify letrozole (LE) and its metabolite, bis-4-cyanophenylmethanol (ME) in urine samples (without any additional treatment) by micellar electrokinetic capillary chromatography (MEKC). In an effort to improve the selectivity and sensitivity of the method, the chemical and instrumental parameters were optimized. The best conditions were: 70 mM borate buffer (pH 9.2) and 40 mM SDS as BGE, 25 kV and 20 degrees C as working voltage and temperature, respectively, with hydrodynamic injection for 6 s. The reliability of the proposed method was also proved by means of a validation procedure based on precision, accuracy, linearity, LOD (15 microg/L for both of them) and LOQ studies. Moreover, an innovatory experimental and statistical design approach, upon a Plackett-Burman fractional factorial model, which involves the simultaneous evaluation of the global robustness and ruggedness effects, was applied. As it has been already stated, the proposed method has been successfully used to directly quantify both compounds in human urine samples, without any additional treatment, but the previously reached LOD and LOQ values can be improved by applying an SPE preconcentration procedure, also developed and optimized by the authors in this work. Real determinations of these analytes in clinical urines of a patient under LE treatment were performed, too.

Extremely slow formate elimination in severe methanol poisoning: a fatal case report.

UNLABELLED: Methanol poisoning is a potentially fatal medical emergency because of its metabolism to formic acid. The half-life of formate has been reported in the range of 2.5-12.5 hours, but the degree of inter-individual variation is not known. We studied methanol and formate kinetics in a case of late diagnosed methanol poisoning with persisting metabolic acidosis and circulatory failure. CASE REPORT: A 63-year-old man was referred to our hospital with a tentative diagnosis of stroke. He was awake on admission, but he soon deteriorated in the emergency department and a metabolic acidosis was revealed. Methanol poisoning was then suspected approximately five hours after admission but in spite of intensive treatment he died after six days. RESULTS: The S-methanol half-lives during treatment with fomepizole before and during hemodialysis were 49.5 and 4.1 hours, respectively, while the similar half-lives of S-formate were 77.0 and 2.9 hours. S-fomepizole was measured and found to be within the therapeutic range during treatment. DISCUSSION: The patient was treated with the established dosing regimen for fomepizole and the measured S-fomepizole levels throughout the treatment were adequate; the S-methanol elimination also suggests that methanol metabolism was blocked. Hence, other explanations for this exceptionally long formate half-life include slow formate metabolism, due to small hepatic folate stores or to genetic deficiencies in formate-metabolizing enzymes, or slow formate excretion, due to renal tubular acidosis, to a non-oliguric renal failure, or to genetic deficiencies in the renal formate transporters. CONCLUSION: This case report indicates that the half-life of S-formate may have greater inter-individual variation than earlier expected, being by far the longest half-life reported in the medical literature. These results support the use of hemodialysis in the treatment of such patients.