New metabolites of 2-ethylhexyl salicylate in human urine after simulated real-life dermal sunscreen application.

2-Ethylhexyl salicylate (EHS) is an organic UV filter which is used in sunscreen and other personal care products. The dermal uptake of EHS was studied in several dermal-exposure experiments. This paper aims to coherently assess urine samples after dermal exposure for the biomarkers EHS, 5OH-EHS, 5oxo-EHS, and 5cx-EPS as well as further biomarkers of interest, specifically 4OH-EHS, 4oxo-EHS, 2OH-EHS, and 6OH-EHS, for the first time. Samples from 18 participants of a pre-existing dermal exposure study under real-life conditions were reassessed using a comprehensive LC-MS/MS method. EHS accounts for 34 % of the cumulative excretion of all analytes within 24 h after exposure, followed by 5OH-EHS (19 %), 5cx-EPS (18 %), 4OH-EHS (15 %) and 5oxo-EHS (11 %). Further metabolites were only quantified in minor amounts. EHS as the most prominent excretion parameter in this study demonstrates the missing first-pass effect after dermal absorption. Furthermore, the applied novel comprehensive analytical procedure revealed oxidation at the ω (5cx-EPS, 6OH-EHS), ω-1 (5OH-EHS, 5oxo-EHS), and ω-2 positions (4OH-EHS, 4oxo-EHS) in the main chain of the ethylhexyl group as well as oxidation in the side chain (2OH-EHS). The presented data are of high relevance for a reliable toxicological risk assessment of dermal exposure to EHS.

Comprehensive assessment of the UV-filter 2-ethylhexyl salicylate and its phase I/II metabolites in urine by extended enzymatic hydrolysis and on-line SPE LC-MS/MS.

2-ethylhexyl salicylate (EHS) is used as a UV filter in personal-care products, such as sunscreen, to prevent skin damage through UV radiation. The application of EHS-containing products leads to systemic EHS absorption, metabolization and excretion. To measure EHS and its corresponding metabolite levels in urine, a comprehensive analytical procedure based on an extended enzymatic hydrolysis, on-line-SPE, and UPLC-MS/MS was developed. The method covers a large profile of seven metabolites (including isomeric structures) as well as EHS itself in a run time only of 18 min. Easy sample preparation, consisting of a 2-h hydrolysis step, followed by on-line enrichment and purification, add to the efficiency of the method. An update, compared to a previous method for the determination of EHS and metabolites in urine, is that, during hydrolysis, both glucuronide and sulfate conjugates are considered. The method was furthermore applied to urine samples after a real-life exposure scenario to EHS-containing sunscreen. The method is highly sensitive with limits of detection ranging from 6 to 65 ng/L. Moreover, it is characterized by good precision data, accuracy, and robustness to matrix influences. Application of the method to urine samples following dermal exposure to an EHS-containing sunscreen revealed EHS as the main biomarker after dermal exposure, followed by the major biomarkers 5OH-EHS, 5cx-EPS, 4OH-EHS and 5oxo-EHS. The expansion and optimization of this method decisively contributes to the research on the dermal metabolism of EHS and can be applied in exposure studies and for human biomonitoring.

Effect of low salicylate diet on clinical and inflammatory markers in patients with aspirin exacerbated respiratory disease - a randomized crossover trial.

BACKGROUND: Aspirin-exacerbated respiratory disease (AERD) is characterized by eosinophilic rhinosinusitis, nasal polyposis, and bronchial asthma, along with the onset of respiratory reactions after the ingestion of nonsteroidal anti-inflammatory drugs (NSAIDs) or acetylsalicylic acid (ASA). In addition to the therapeutic routines and surgical options available, a low dietary intake of food salicylate has been suggested as adjunctive therapy for this condition. This study aimed to assess the influence of a short-term low salicylate diet on inflammatory markers in patients with AERD and whether that would result in symptomatic improvement. METHODS: Prospective study with randomization to either a high or low salicylate diet for 1 week, followed by cross-over to the other study arm. Participants were asked to record their dietary salicylate for each week of the study. Urinary creatinine, salicylate and leukotriene levels were measured at the time of recruitment, end of week one and end of week two and the SNOT-22 questionnaire was filled out at the same time points. RESULTS: A total of seven participants completed the study. There was no statistical difference in the urinary salicylate and leukotriene levels between the two diets; nevertheless, participants on low salicylate diet reported improved SNOT-22 symptoms scores (p = 0.04), mainly in the rhinologic, ear/facial, and sleep dysfunction symptom domains. In addition, these last two domains outcomes were more significant than the minimal clinically important difference. CONCLUSIONS: A short-term low salicylate diet may not result in biochemical outcomes changes but seems to provide significant symptomatic relief for patients with AERD. TRIAL REGISTRATION: NCT01778465 ( www.clinicaltrials.gov ).

Human volunteer study of the decontamination of chemically contaminated hair and the consequences for systemic exposure.

The decontamination of exposed persons is a priority following the release of toxic chemicals. Efficacious decontamination reduces the risk of harm to those directly affected and prevents the uncontrolled spread of contamination. Human studies examining the effectiveness of emergency decontamination procedures have primarily focused on decontaminating skin, with few examining the decontamination of hair and scalp. We report the outcome of two studies designed to evaluate the efficacy of current United Kingdom (UK) improvised, interim and specialist mass casualty decontamination protocols when conducted in sequence. Decontamination efficacy was evaluated using two chemical simulants, methyl salicylate (MeS) and benzyl salicylate (BeS) applied to and recovered from the hair of volunteers. Twenty-four-hour urinary MeS and BeS were measured as a surrogate for systemic bioavailability. Current UK decontamination methods performed in sequence were partially effective at removing MeS and BeS from hair and underlying scalp. BeS and MeS levels in urine indicated that decontamination had no significant effect on systemic exposure raising important considerations with respect to the speed of decontamination. The decontamination of hair may therefore be challenging for first responders, requiring careful management of exposed persons following decontamination. Further work to extend these studies is required with a broader range of chemical simulants, a larger group of volunteers and at different intervention times.

A controlled cross-over study to evaluate the efficacy of improvised dry and wet emergency decontamination protocols for chemical incidents.

The UK Initial Operational Response (IOR) to chemical incidents includes improvised decontamination procedures, which use readily available materials to rapidly reduce risk to potentially exposed persons. A controlled, cross-over human volunteer study was conducted to investigate the effectiveness of improvised dry and wet decontamination procedures on skin, both alone, and in sequence. A simulant contaminant, methyl salicylate (MeS) in vegetable oil with a fluorophore was applied to three locations (shoulder, leg, arm). Participants then received no decontamination (control) or attempted to remove the simulant using one of three improvised protocols (dry decontamination; wet decontamination; combined dry and wet decontamination). Simulant remaining on the skin following decontamination was quantified using both Gas Chromatography Tandem Mass Spectrometry (GC-MSMS) for analysis of MeS and UV imaging to detect fluorophores. Additionally, urine samples were collected for 24 hours following application for analysis of MeS. Significantly less simulant was recovered from skin following each improvised decontamination protocol, compared to the no decontamination control. Further, combined dry and wet decontamination resulted in lower recovery of simulant when compared to either dry or wet decontamination alone. Irrespective of decontamination protocol, significantly more simulant remained on the shoulders compared to either the arms or legs, suggesting that improvised decontamination procedures are less effective for difficult to reach areas of the body. There was no effect of decontamination on excreted MeS in urine over 24 hours. Overall, findings indicate that improvised decontamination is an effective means of rapidly removing contaminants from skin, and combinations of improvised approaches can increase effectiveness in the early stages of decontamination and in the absence of specialist resources at an incident scene. However, the variable control and consistency of improvised decontamination techniques means that further intervention is likely to be needed, particularly for less accessible areas of the body.

Analysis of Chemical Simulants in Urine: A Useful Tool for Assessing Emergency Decontamination Efficacy in Human Volunteer Studies.

INTRODUCTION: To date, all human studies of mass-casualty decontamination for chemical incidents have relied on the collection and analysis of external samples, including skin and hair, to determine decontamination efficacy. The removal of a simulant contaminant from the surface of the body with the assumption that this translates to reduced systemic exposure and reduced risk of secondary contamination has been the main outcome measure of these studies. Some studies have investigated systemic exposure through urinary levels of simulant metabolites. The data obtained in these studies were confounded by high background concentrations from dietary sources. The unmetabolized simulants have never been analyzed in urine for the purposes of decontamination efficacy assessment. STUDY OBJECTIVE: Urinary simulant analysis could obviate the need to collect skin or hair samples during decontamination trials and provide a better estimate of both decontamination efficacy and systemic exposure. The study objective therefore was to determine whether gross skin contamination as part of a decontamination study would yield urine levels of simulants sufficient to evaluate systemic availability free from dietary confounders. METHODS: In this study, a gas chromatography-tandem mass spectrometry method was developed for the analysis of two chemical simulants, methyl salicylate (MeS) and benzyl salicylate (BeS), in urine. An extraction and sample clean-up method was validated, enabling quantitation of these simulants in urine. The method was then applied to urine collected over a 24-hour period following simulant application to the skin of volunteers. RESULTS: Both MeS and BeS were present in all urine samples and were significantly increased in all post-application samples. The MeS levels peaked one hour after skin application. The remaining urinary levels were variable, possibly due to additional MeS exposures such as inhalation. In contrast, the urinary excretion pattern for BeS was more typical for urinary excretion curves, increasing clearly above baseline from four hours post-dose and peaking between 12.5 and 21 hours, a pattern consistent with dermal absorption and rapid excretion. CONCLUSION: The authors propose BeS is a useful simulant for use in decontamination studies and that its measurement in urine can be used to model systemic exposures following skin application and therefore likely health consequences.

Toxicokinetics of urinary 2-ethylhexyl salicylate and its metabolite 2-ethyl-hydroxyhexyl salicylate in humans after simulating real-life dermal sunscreen exposure.

Chemical UV filters are common components in sunscreens and cosmetic products. The question of adverse health risks is not completely resolved, partly owing to lacking human data from dermal exposure, which are essential for sound risk assessment. Therefore, we investigated the urinary toxicokinetics of 2-ethylhexyl salicylate (EHS) after a 1-day dermal real-life sunscreen application scenario. Twenty human volunteers were dermally exposed to a commercial sunscreen for 9 h under real-life conditions (2 mg/cm2 body surface area; double re-application; corresponding to 3.8 g EHS). Urine samples were analyzed for EHS and one of its specific metabolites 2-ethyl-5-hydroxyhexyl salicylate (5OH-EHS) using a two-dimensional liquid chromatographic electrospray-ionization tandem mass spectrometric procedure. EHS and 5OH-EHS were excreted after sunscreen application and reached up to 525 µg/g and 213 µg/g creatinine, respectively. The toxicokinetic models showed concentration peaks between 7 and 8 h after first application. First-phase terminal half-lives were 8-9 h. For 5OH-EHS, a second-phase terminal half-life could be determined (87 h). EHS and 5OH-EHS showed a faster elimination with 70-80% of the overall excretion occurring within 24 h after application compared to more lipophilic UV filters. Cumulative excreted amounts over 24 h reached up to 334 µg EHS and 124 µg of 5OH-EHS. Simulated real-life sunscreen use for 1 day leads to the bioavailability of the UV filter EHS in humans. The kinetic profiles with a prolonged systemic availability indicate a skin depot and make accumulation during consecutive multi-day exposure likely.

Quantification of prominent organic UV filters and their metabolites in human urine and plasma samples.

Monitoring human exposure to chemical UV filters is essential for an accurate assessment of the health risk caused by the resorbed compounds. We developed different procedures for the determination of the prominent UV filters octocrylene (OC), avobenzone (AVO) and 2-ethylhexyl salicylate (EHS) as well as for two OC and EHS metabolites in human urine and OC, AVO and 2-cyano-3,3-diphenylacrylic acid (CDAA) in plasma samples using liquid chromatography-tandem mass spectrometry (LC-MS/MS). Since the development of a multi-method for all analytes proved to be difficult, three different procedures were established for the determination of AVO, OC and its metabolite CDAA in urine and plasma as well as for EHS and its metabolite 5-hydroxy-EHS in urine. The methods have been validated with good sensitivity, precision and accuracy. The procedures were satisfactorily applied to the determination of the target compounds in human samples collected from volunteers after sunscreen application. These new analytical procedures can provide information on the internal exposure to the UV filters OC, AVO and EHS, which has been little studied.

Determination of metabolites of the UV filter 2-ethylhexyl salicylate in human urine by online-SPE-LC-MS/MS.

The UV filter 2­ethylhexyl salicylate (EHS) is widely used in sunscreens and other personal care products (PCP). EHS has been detected in a variety of environmental matrices. However, data on the internal EHS exposure in humans is not available, due to the lack of exposure biomarkers and analytical methods for their determination. Here, we report a method for the determination of three oxidative EHS metabolites in human urine: 2­ethyl­5­hydroxyhexyl 2­hydroxybenzoate (5OH-EHS), 2­ethyl­5­oxohexyl 2­hydroxybenzoate (5oxo-EHS), and 5­(((2­hydroxybenzoyl)oxy)methyl)heptanoic acid (5cx-EPS). Urine samples are incubated with ß­glucuronidase and analyzed by liquid chromatography-electrospray ionization-triple quadrupole-tandem mass spectrometry, coupled with online sample clean-up and analyte enrichment using turbulent flow chromatography (online-SPE-LC-MS/MS). Quantification is performed by stable isotope dilution analysis, using deuterium-labeled standards of each of the three metabolites. The described method is precise (coefficient of variation <5% within-series and interday), accurate (mean relative recoveries between 96% and 105%), and sensitive, with limits of quantification (LOQ) of 0.01 µg/L (5cx-EPS), 0.05 µg/L (5OH-EHS), and 0.15 µg/L (5oxo-EHS). After dermal application of an EHS containing sunscreen to a human volunteer, we were able to quantify all three metabolites in urine samples collected post application, showing clear elimination kinetics. In spot urine samples from the general population (n = 35) we were able to quantify EHS biomarkers in 91% of all samples, with highest concentrations in individuals (n = 11) who stated use of PCPs containing UV filters within 5 days prior to sampling. We will apply the method for investigating human EHS metabolism and in future human biomonitoring studies for EHS exposure and risk assessment.

Quantitative determination of five metabolites of aspirin by UHPLC-MS/MS coupled with enzymatic reaction and its application to evaluate the effects of aspirin dosage on the metabolic profile.

Acetylsalicylic acid (Aspirin, ASA) is a famous drug for cardiovascular diseases in recent years. Effects of ASA dosage on the metabolic profile have not been fully understood. The purpose of our study is to establish a rapid and reliable method to quantify ASA metabolites in biological matrices, especially for glucuronide metabolites whose standards are not commercially available. Then we applied this method to evaluate the effects of ASA dosage on the metabolic and excretion profile of ASA metabolites in rat urine. Salicylic acid (SA), gentisic acid (GA) and salicyluric acid (SUA) were determined directly by UHPLC-MS/MS, while salicyl phenolic glucuronide (SAPG) and salicyluric acid phenolic glucuronide (SUAPG) were quantified indirectly by measuring the released SA and SUA from SAPG and SUAPG after ß-glucuronidase digestion. SUA and SUAPG were the major metabolites of ASA in rat urine 24h after ASA administration, which accounted for 50% (SUA) and 26% (SUAPG). When ASA dosage was increased, the contributions dropped to 32% and 18%, respectively. The excretion of other three metabolites (GA, SA and SAPG) however showed remarkable increases by 16%, 6% and 4%, respectively. In addition, SUA and SUAPG were mainly excreted in the time period of 12-24h, while GA was excreted in the earlier time periods (0-4h and 4-8h). SA was mainly excreted in the time period of 0-4h and 12-24h. And the excretion of SAPG was equally distributed in the four time periods. We went further to show that the excretion of five metabolites in rat urine was delayed when ASA dosage was increased. In conclusion, we have developed a rapid and sensitive method to determine the five ASA metabolites (SA, GA, SUA, SAPG and SUAPG) in rat urine. We showed that ASA dosage could significantly influence the metabolic and excretion profile of ASA metabolites in rat urine.

THE LABORATORY ASPECTS OF PROTEINURIA.

INTRODUCTION: The existence of proteinuria may be overlooked by applying the test strips. The aim of this study has been to determine the discrepancy between the findings ofproteinuria detected by test strips when compared to the results of its testing with the sulfosali- cylic acid. MATERIAL AND METHODS: The study sample consisted of 1106 subjects, who were divided into the proteinuria positive (test strips showed the presence of isolated proteinuria), and proteinuria negative group (microscopic examination revealed the presence of ≥10 fresh red blood cells4sL, and/or ≥1 dysmorphic erythrocyte/µL, and/or 10≥ leukocytes4uL, and or ≥1 cylinder, and/or ≥ 1 nonsquamous epithelial cells4µL, and/or ≥100 bacteria/µL). Both groups had the urine tested with sulfosalicylic acid. The chemical and microscopic examination of the urine was done by the analyzer LabUMat-UriSed. RESULTS: Proteinuria was confirmed with the sulfosalicylic acid test in 96.5% ofsublects from group I and in 85.3% ofsubiects from group 2. Among the patients with the negative finding of proteinuria on the test strip and with the positive sulfosalicylic acid test there was a significantly higher number of those with pathological findings of erythrocytes, leukocytes, bacteria and cylinders in the urine when compared to those of the same group with negative sulfosalicylic acid test. CONCLUSION: Sulfosalicylic acid test should be performed in cases of pathological microscopic findings in the urine in case of the presence of ≥10 fresh erythrocytes4iL and/or ≥ 1 dysmorphic eryth- rocyte/pL and/or 10≥ leukocytes/µL and/or 1≥ cylinder (except hyaline) and/or ≥1 nonsquamous epithelial cells/pL and/or≥ 100 bacterial pL even if the test strip examination is negative for proteinuria.

Preclinical pharmacokinetic evaluation and metabolites identification of methyl salicylate-2-O-ß-d-lactoside in rats using LC-MS/MS and Q-TOF-MS methods.

Methyl salicylate-2-O-ß-d-lactoside (MSL) is a natural salicylate derivative from the traditional Chinese medicine of Gaultheria yunnanensis (Franch.) Rehder (G. yunnanensis). As a non-steroidal anti-inflammatory drug (NSAID), MSL exerts a significant anti-arthritis effect but hardly has any gastrointestinal toxicity. In this paper, the pharmacokinetics, distribution, excretion and identification of MSL and its metabolites are described following rat oral and intravenous administration. The biological samples were quantified by UPLC-MS/MS and the metabolites in urine and feces were identified by using Q-TOF-MS. These results will support future investigations leading to clinical development of this drug.

Attitudes to mesalamine questionnaire: a novel tool to predict mesalamine nonadherence in patients with IBD.

OBJECTIVES: Poor adherence to mesalamine is common and driven by a combination of lifestyle and behavioral factors, as well as health beliefs. We sought to develop a valid tool to identify barriers to patient adherence and predict those at risk for future nonadherence. METHODS: A 10-item survey was developed from patient-reported barriers to adherence. The survey was administered to 106 patients with ulcerative colitis who were prescribed mesalamine, and correlated with prospectively collected 12-month pharmacy refills (medication possession ratio (MPR)), urine levels of salicylates, and self-reported adherence (Morisky Medication Adherence Scale (MMAS)-8). RESULTS: From the initial 10-item survey, 8 items correlated highly with the MMAS-8 score at enrollment. Computer-generated randomization produced a derivation cohort of 60 subjects and a validation cohort of 46 subjects to assess the survey items in their ability to predict future adherence. Two items from the patient survey correlated with objective measures of long-term adherence: their belief in the importance of maintenance mesalamine even when in remission and their concerns about side effects. The additive score based on these two items correlated with 12-month MPR in both the derivation and validation cohorts (P<0.05). Scores on these two items were associated with a higher risk of being nonadherent over the subsequent 12 months (relative risk (RR) =2.2, 95% confidence interval=1.5-3.5, P=0.04). The area under the curve for the performance of this 2-item tool was greater than that of the 10-item MMAS-8 score for predicting MPR scores over 12 months (area under the curve 0.7 vs. 0.5). CONCLUSIONS: Patients' beliefs about the need for maintenance mesalamine and their concerns about side effects influence their adherence to mesalamine over time. These concerns could easily be raised in practice to identify patients at risk of nonadherence (Clinical Trial number NCT01349504).

The utility of urine sulphosalicylic acid testing in the detection of non-albumin proteinuria.

We report two cases of immunoglobulin light chain proteinuria (Bence Jones proteinuria) detected by simple side-room invest-igations: urine dipstick negative/1+, but with strong positive pre-cipitation on addition of an equal volume of sulphosalicylic acid (SSA) 3%. We highlight a significant limitation of urine dipstick testing, namely specificity for albumin, and the utility of SSA testing for the detection of urinary free light chain immunoglobulins.

Predictors of adherence to secondary preventive medication in stroke patients.

OBJECTIVE: The purpose of this study is to identify factors which predict adherence in stroke survivors. DESIGN: This is a longitudinal study where 180 stroke survivors were assessed 1 year after their first ischaemic stroke. The relationship between adherence and illness and medication beliefs was tested at baseline (time 1) and again 5-6 weeks later (time 2). MAIN OUTCOME MEASURES: The main outcome measures used in this study are Medication Adherence Report Scale and urinary salicylate levels. RESULTS: Four variables predicted time 1 poor adherence: (1) younger age, (2) increased specific concerns about medications, (3) reduced cognitive functioning and (4) low perceived benefit of medication. Three out of these four variables were again predictive of time 2 adherence and accounted for 24% of the variance: (1) younger age, (2) increased specific concerns about medications and (3) low perceived benefit of medication. The urinary salicylate assay failed to differentiate between patients taking and not taking aspirin. CONCLUSION: Interventions to improve adherence should target patients' beliefs about their medication.

Nephrotic syndrome occurring during tiopronin treatment for cystinuria.

Cystinuria is an autosomal recessive disorder characterized with abnormal tubular reabsorption of cystine and dibasic amino acids leading to cystine urolithiasis. The classical form is caused by mutations in the SLC3A1 gene (OMIM 220100). The cornerstone of the treatment is high hydration and alkalization of the urine to achieve urine pH between 7.0 and 7.5, at which point, cystine solubility in the urine is optimal. These measures very often fail, and thus addition of sulfhydryl agents like penicillamine and tiopronin (mercaptopropionyl glycine) is recommended. Herein, we report a 3-year-old boy with cystinuria resulting in recurrent nephrolithiasis requiring surgery and extracorporeal shock wave lithotripsy. Nine months after introduction of tiopronin, the boy manifested generalized edema, oliguria, and biochemical indices of nephrotic syndrome. Tiopronin was withdrawn, and the boy was given only supportive treatment. Within 10 days, he entered into clinical and biochemical remission. Pediatricians should be aware of this adverse effect of tiopronin, and therefore, testing of the urine with strips or sulfosalicylic acid at least once weekly at home may be very helpful for early detection of proteinuria.

[Development of salicylic acid dipstick test].

A dipstick test was successfully devised for the screening of salicylic acid in urine. It, named "salicylic acid dipstick test", is TLC plastic sheet which was soaked into 5% (w/v) of ferric chloride aqueous solution, then was covered with Oblate and dried. The test paper was dipped into the sample, then it immediately turned purple under the condition of more than 100 microg/ml of salicylic acid in urine. This device was useful for the emergency screening of salicylic acid in acute poisoning cases with aspirin.

Increased salicylate concentrations in urine of human volunteers after consumption of cranberry juice.

The aim of this study was to assess whether regular consumption of cranberry juice results in elevations in urinary salicylate concentrations in persons not taking salicylate drugs. Two groups of healthy female subjects (11/group) matched for age, weight, and height consumed 250 mL of either cranberry juice or a placebo solution three times a day (i.e., 750 mL/day) for 2 weeks. At weekly intervals, salicylic acid and salicyluric acid (the major urinary metabolite of salicylic acid) concentrations were determined in urine by HPLC with electrochemical detection. Concentrations of salicylic acid in plasma were also determined. Consumption of cranberry juice was associated with a marked increase (p < 0.001) of salicyluric and salicylic acids in urine within 1 week of the intervention. After 2 weeks, there was also a small but significant (p < 0.05) increase in salicylic acid in plasma. The regular consumption of cranberry juice results in the increased absorption of salicylic acid, an anti-inflammatory compound that may benefit health.

The analysis of methyl salicylate and salicylic acid from Chinese herbal medicine ingestion.

This paper presents a multi-drug fatality in which methyl salicylate was ingested. It is presented to inform the toxicological community that a particularly expeditious method of detection for methyl salicylate exists. Previously published methods for the analysis of methyl salicylate include a gas chromatographic-mass spectrometric method and an alkaline/acidic extraction followed by high-performance liquid chromatographic (HPLC) analysis. This article describes a method for analyzing methyl salicylate using HPLC, in which a simple, rapid extraction procedure is used. Using a previously published HPLC method, methyl salicylate and salicylic acid were easily identified in biological specimens. Methyl salicylate and salicylic acid were detected using an extraction solution of acetonitrile coupled with internal standard and then analyzed by HPLC-diode-array detection. Because of its concentrated liquid form, methyl salicylate ingestion can cause rapid onset salicylate toxicity. As the potentially fatal methyl salicylate forms are readily available and easily found on drugstore shelves, the need to rapidly detect and quantitate salicylic acid concentrations that are due to methyl salicylate ingestion may arise. In the case presented, the peripheral blood concentration of salicylic acid from methyl salicylate ingestion was 320 mg/L, and the concentration in gastric contents was 820 mg. It alone was not the cause of death, however. The discovery of the ability to detect and quantitate methyl salicylate was due to its suspected ingestion.

Pattern of occurrence of microalbuminuria among dippers and non-dippers (essential hypertensives) in a Nigerian university teaching hospital.

OBJECTIVES: Hypertensives who fail to manifest the normal circadian nocturnal fall in blood pressure have a higher incidence of cardiovascular complications, early glomerular injury and microalbuminuria. This study aims to quantify the proportion of dippers and non-dippers among the essential hypertensive population, and determine the frequency of occurrence of micro-albuminuria among them. MATERIALS AND METHODS: Early morning urine specimens were taken from 50 patients with essential hypertension and 20 healthy, normotensive subjects. Combined negative results from albustic strip testing and sulfosalicylic acid tests were taken as excluding microalbuminuria. While collecting urine for 24-hour urinary protein and creatinine clearance, hourly blood pressure readings were recorded. Readings obtained between 07:00 and 23:00 were taken as daytime blood pressure readings, whereas readings obtained between 23:00 and 07:00 were considered night-time blood pressure. Dippers were considered to be those patients in whom the difference between mean daytime systolic/diastolic blood pressure and mean night-time systolic/diastolic blood pressure was 10/5mm Hg or more. RESULTS: Thirty-six (72%) and 14 (28%) patients with essential hypertension fulfilled the criteria for dippers and non-dippers, respectively. The night-time systolic and diastolic blood pressures were significantly higher in non-dippers than in dippers (P < 0.05). The mean daytime systolic and diastolic blood pressures were not different between these two groups. Twenty-nine out of 36 (80.6%) urinary specimens from dippers were without microalbuminuria, against six out of 14 (42.9%) specimens from non-dippers, p < 0.05. Eighteen out of 20 controls (90%) were without microalbuminuria. CONCLUSION: This study demonstrated that about 28% of the local essential hypertensive population was non-dippers and 57.1% of these had microalbuminuria with the attendant cardiovascular and renal risks.