Breath biomarkers of liver cirrhosis.

The diagnosis of asymptomatic cirrhosis in patients with liver disease is of importance to start screening for complications in due time. Liver biopsy is neither sensitive nor practical enough to be used as a frequent follow-up test in patients with chronic liver disease. The volatile organic compounds present in exhaled breath offer the possibility of exploring internal physiologic and pathologic process in a non invasive way. This study examined whether a specific pattern of biomarkers can be found in breath samples of patients with cirrhosis. To this aim samples of alveolar breath from patients with cirrhosis and healthy volunteers were analyzed using gas chromatography-mass spectrometry. When linear discriminant analysis was used to search for a model(s)/pattern of compounds characteristic for liver cirrhosis, 24 models of 8 independent compounds could distinguish between the groups. The sensitivity and specificity (between 82% and 88%, and 96% and 100%, respectively) of the models suggest that a specific pattern of breath biomarkers can be found in patients with cirrhosis, which may allow detecting this complication of chronic liver disease in an early stage.

Dancing on coke: smuggling cocaine dispersed in polyvinyl alcohol.

Recent trends suggest that cocaine smugglers have become more and more inventive to avoid seizures of large amounts of cocaine transported between countries. We report a case of a mail parcel containing a dance pad which was seized at the Customs Department of Brussels Airport, Belgium. After investigation, the inside of the dance pad was found to contain a thick polymer, which tested positive for cocaine. Analysis was performed using a routine colorimetric swipe test, gas chromatography coupled with mass spectrometry and nuclear magnetic resonance spectroscopy. The polymer was identified as polyvinyl alcohol (PVA) and contained 18% cocaine, corresponding to a street value of € 20,000. Laboratory experiments showed that cocaine could be easily extracted from the PVA matrix. This case report reveals a new smuggling technique for the transportation of large amounts of cocaine from one country to another.

Chloral hydrate intoxication in a 3-month-old child: avoidance of hemodialysis by an immediate determination of trichloroethanol.

BACKGROUND: Chloral hydrate is used worldwide as a first-line agent for procedural sedation in paediatric patients undergoing painless diagnostic investigations. Chloral hydrate overdoses in children and adults have been reported to cause various toxicities, including central nervous system, respiratory and cardiac depression with sometimes fatal outcome. PATIENT AND METHODS: A 3-month-old girl was admitted after an unintentional administration of a 10-fold dose of chloral hydrate (667 mg/kg). She showed respiratory insufficiency in need of intubation and ventilation. Gastric endoscopy revealed esophagitis and gastric ulcerations. To assess the need for hemodialysis, serum trichloroethanol (TCE) was determined using a mass spectrometric quantification after a methyl tertiary butyl ether extraction using an external standard method. The serum TCE level 6 h after administration was 89 mg/L and declined to 20 mg/L within 24 h. The child could be extubated the next day; her further course was uneventful. CONCLUSION: The repeated determination of serum TCE levels prevented a technically difficult and risky hemodialysis in this very young patient.

GC-MS analysis of breath odor compounds in liver patients.

BACKGROUND: Liver diseases can cause a sweet, musty aroma of the breath, called fetor hepaticus. Even in a stage of cirrhosis, the disease can be asymptomatic for many years. Breath analysis might be helpful to detect occult liver pathology. STUDY OBJECTIVE: This study examined whether specific breath odor compounds can be found in liver patients, suffering from cirrhosis, which might be useful for diagnosis. MATERIALS AND METHODS: Fifty-two liver patients and 50 healthy volunteers were enrolled. Alveolar air was analyzed by gas chromatography-mass spectrometry. Using discriminant analysis a model for liver disease was built. RESULTS: Dimethyl sulfide, acetone, 2-butanone and 2-pentanone were increased in breath of liver patients, while indole and dimethyl selenide were decreased. Sensitivity and specificity of the model were respectively 100% and 70%. CONCLUSIONS: Fetor hepaticus is caused by dimethyl sulfide and to a lower extent by ketones in alveolar air. Breath analysis by GC-MS makes it possible to discriminate patients with breath malodor related to hepatic pathologies.

Comparison of electron and chemical ionization modes by validation of a quantitative gas chromatographic-mass spectrometric assay of new generation antidepressants and their active metabolites in plasma.

A gas chromatographic-mass spectrometric method (GC-MS) for the simultaneous determination of the 'new' antidepressants (mirtazapine, viloxazine, venlafaxine, trazodone, citalopram, mianserin, reboxetine, fluoxetine, fluvoxamine, sertraline, maprotiline, melitracen, paroxetine) and their active metabolites (desmethylmirtazapine, O-desmethylvenlafaxine, m-chlorophenylpiperazine, desmethylcitalopram, didesmethylcitalopram, desmethylmianserin, desmethylfluoxetine, desmethylsertraline, desmethylmaprotiline) in plasma using different ionization modes was developed and validated. Sample preparation consisted of a strong cation exchange mechanism and derivatisation with heptafluorobutyrylimidazole. The GC separation was performed in 24.8 min. Identification and quantification were based on selected ion monitoring in electron (EI) and chemical ionization (CI) modes. Calibration by linear and quadratic regression for electron and chemical ionization, respectively, utilized deuterated internal standards and a weighing factor 1/x(2). Limits of quantitation were established between 5 and 12.5 ng/ml in EI and positive ionization CI (PICI), and 1 and 6.25 ng/ml in negative ionization CI (NICI). During validation stability, sensitivity, precision, accuracy, recovery, and selectivity were evaluated for each ionization mode and were demonstrated to be acceptable for most compounds. While it is clear that not all compounds can be quantitated either due to chromatographic (trazodone) or derivatisation problems (O-desmethylvenlafaxine), this method can quantitate most new antidepressants (ADs) in the therapeutic range using EI. PICI and NICI lead to higher selectivity. Moreover, NICI is of interest for small sample volumes and high sensitivity requirements. This paper draws the attention to the pros and cons of the different ionization modes in the GC-MS analysis of these antidepressants in plasma.

Halitosis associated volatiles in breath of healthy subjects.

BACKGROUND: Halitosis can have an intra- or extra-oral origin. In all cases, bad breath is caused by the presence of volatile organic compounds originating from the mouth or the expired air. They can be specific for certain diseases or infections. STUDY OBJECTIVE: This study explored the presence and concentration of these volatile compounds normally associated with halitosis in the breath of healthy symptomless volunteers. METHODS: Alveolar and mouth air of 40 healthy volunteers as well as environmental air were analyzed by gas chromatography-mass spectrometry (GC-MS) and by a commercially available GC device (OralChroma). RESULTS: 14 compounds, associated with halitosis could be detected. All of them except carbon disulfide, appeared to be (partly) produced endogenously and/or in the mouth. Acetone, 2-butanone, 2-pentanone and 1-propanol were common to all volunteers in both alveolar and mouth air and indole and dimethyl selenide in alveolar air. CONCLUSIONS: GC-MS seems a promising tool for differential diagnosis of halitosis, with the possibility to detect extra-oral causes, which often remain undetected unless characterized by a specific smell.

Differences between alveolar air and mouth air.

Our breath contains an intraoral and an alveolar part, the latter being the last to be exhaled. As such, major differences in composition can be expected, with for alveolar air the inclusion of more metabolic compounds released during the blood-air exchange. This study explored the differences between breath air from the oropharynx and from the lungs in healthy volunteers. Mouth and alveolar air of 40 volunteers was analyzed using gas chromatography-mass spectrometry, together with a sample of room air. A chromatogram of a single person contains on average 145 different compounds. Altogether, 618 compounds were detected. A total of 35 compounds were common to all volunteers. The number of compounds was significantly higher in mouth air than in alveolar air. For 47 compounds, very significant differences in detection/concentration were recorded. Gas chromatography-mass spectrometry offers a detailed overview of the compounds in a person's breath. One should be aware of the distinction between alveolar air and oropharyngeal air.

Analysis of gamma-hydroxybutyric acid, DL-lactic acid, glycolic acid, ethylene glycol and other glycols in body fluids by a direct injection gas chromatography-mass spectrometry assay for wide use.

Analysis of blood of severely intoxicated patients always requires prompt investigation. Diagnosis of intoxication with ethylene glycol, gamma-hydroxybutyric acid or D-lactic acid takes hours, since several different procedures are required. Rapid derivatization of the common hydroxyl function may resolve this analytical problem. Here we describe a fast method for the simultaneous measurement of ethylene glycol, glycolic acid, gamma-hydroxybutyric acid and racemic lactic acid. Only 20 microl of serum, plasma or urine are required for immediate derivatization at 70 degrees C with 750 microl of bis-N,O-trimethylsilyl trifluoroacetamide after adding 20 microl of internal standard solution (1,3-propylene glycol) and 20 microl of the catalyst dimethylformamide. After centrifugation an aliquot is transferred to a gas chromatographic system and analyzed with electron-impact mass spectrometry in selective ion monitoring mode. The derivatized acids and ethylene glycol are well separated and detected with a limit of detection ranging from 0.12 mg/l for ethylene glycol to 0.95 mg/l for gamma-hydroxybutyric acid, while the limit of quantification ranged from 0.4 mg/l for ethylene glycol to 3.15 mg/l for gamma-hydroxybutyric acid. The method is linear from 0.5 to 1800 mg/l blood for ethylene glycol, from 0.7 to 1200 mg/l for lactic acid, from 1.2 to 1800 mg/l for glycolic acid, and from 3.2 to 200 mg/l for gamma-hydroxybutyric acid, with analytical recoveries, accuracy, day-to-day and within-day precision well within the required limits. Total analysis time with one calibrator was 30 min, derivatization time included. This method is very suitable for emergency toxicology, since several toxic substances can be quantified simultaneously in a fast and sensitive manner.