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Simultaneous administration of lactulose and 51Cr-ethylenediaminetetraacetic acid. A test to distinguish colonic from small-intestinal permeability change.

In normal adults intestinal permeation of ingested 51Cr-ethylenediaminetetraacetic acid (EDTA) is greater than that of lactulose. This difference is abolished in patients with ileostomies, suggesting that it results from colonic permeation of 51Cr-EDTA, which, unlike lactulose, resists bacterial degradation. To investigate the effect of an increase in colonic permeability on absorption of the two molecules, lactulose (5 g) and 51Cr-EDTA (50 microCi) were given orally in isosmolar solution to 11 patients with colitis, and their 24-h urinary excretion measured. By comparison the effect of an increase in small-intestinal permeability induced by ingestion of a hyperosmolar solution (4240 mosm/l) was measured in 10 healthy adults. Hyperosmolar stress increased the 24-h urinary excretion of 51Cr-EDTA above the normal mean + 2 standard deviations (3.31%) in all 10 healthy subjects, and in all of these excretion of lactulose was also increased (greater than 1.06%). In contrast, although seven colitics had a urinary excretion of 51Cr-EDTA above the normal mean + 2 SD, in only two of these patients was recovery of lactulose increased. This suggests that simultaneous administration of lactulose and 51Cr-EDTA may enable permeability changes affecting the colon alone to be distinguished from those involving the small intestine.

Adult↗

Comparison of probiotics and lactulose in the treatment of minimal hepatic encephalopathy in rats.

AIM: To compare the efficacy of probiotic preparation Golden Bifid and lactulose on rat experimental model of minimal hepatic encephalopathy (MHE) induced by thioactamide (TAA). METHODS: MHE was induced by intraperitoneal injection of TAA (200 mg/kg) every 24 h for two consecutive days. Thirty-six male MHE models were then randomly divided into 3 groups: TAA group (n = 12) received tap water ad libitum only; lactulose group (n = 12) and probiotics group (n = 12) were gavaged, respectively with 8 mL/kg of lactulose and 1.5 g/kg of probiotic preparation Golden Bifid (highly concentrated combination of probiotic) dissolved in 2 mL of normal saline, once a day for 8 d (from the 5(th) d before the experiment to the 3(rd) d of the experiment). The latency of brainstem auditory evoked potentials (BAEP) I was used as an objective index of MHE. The incidence of MHE, the level of serum endotoxin, ammonia, liver function and histological grade of hepatic injury of rats were examined individually. RESULTS: There were no overt HE and rat deaths in 3 groups. The incidence of MHE, the levels of blood ammonia and endotoxin in TAA group, which were 83.3% (10/12), 168.33+/-15.44 mg/dL and 0.36+/-0.04 EU/mL, respectively, were significantly higher than those in lactulose group, which were 33.3% (4/12), 110.25+/-7.39 mg/dL and 0.19+/-0.02 EU/mL, and probiotics group, which were 33.3% (4/12), 108.58+/-10.24 mg/dL and 0.13+/-0.03 EU/mL respectively (P<0.001). It showed that either probiotics or lactulose could significantly lower the level of hyperammonemia and hyper-endotoxemia, lighten centrolobular necrotic areas as well as inflammatory reaction in the liver of rats, normalize the latency of BAEP, and decrease the incidence of MHE. However, no significant differences were observed between these two groups (P>0.05). CONCLUSION: Probiotic compound Golden Bifid is at least as useful as lactulose for the prevention and treatment of MHE. Probiotic therapy may be a safe, natural, well-tolerated therapy appropriate for the long-term treatment of MHE.

Ammonia↗

Lactitol in the treatment of chronic hepatic encephalopathy--a randomized cross-over comparison with lactulose.

The effect of lactitol, a new non-absorbable disaccharide, in the treatment of chronic hepatic encephalopathy was assessed in 14 cirrhotic patients with non-selective portosystemic anastomosis in a randomized, cross-over study. At the time of inclusion, all patients showed alterations in mental state, and/or psychometric performance, and in the electroencephalogram. Moreover, 10 out of 14 patients suffered from recurrent episodes of hepatic encephalopathy in the 12 months prior to the study. Patients were randomly treated for two consecutive periods of six months with either lactitol or lactulose. The PSE index was calculated to quantify the neuro-psychiatric impairment. Twelve patients completed the study. The patients required a daily dose of 38.2 g +/- 19 of lactulose or 36.3 g +/- 5 of lactitol to produce two semi-soft stools per day. No deterioration in the mental state or in the other neuro-psychiatric parameters were observed, neither during lactitol nor during lactulose therapy. During the study, mild episodes of recurrent encephalopathy occurred in 60% of the patients taking lactulose, and in 25% of the patients taking lactitol, the difference not being significant (X = 1.54, p = 0.21). Flatulence, the major side-effect noted during the study, was present in 7 of the 12 patients during lactulose treatment, and in 2 patients during lactitol treatment; one patient on lactitol complained of nausea. The side effects which occurred during lactitol of the dosage, while those occurring during lactitol appeared when the dosage was higher than 40 g. Lactitol may be considered at least as effective as lactulose in the treatment of chronic hepatic encephalopathy.

Adult↗

Measurement of intestinal permeability to mannitol and lactulose as a means of diagnosing food allergy and evaluating therapeutic effectiveness of disodium cromoglycate.

Gastrointestinal permeability was evaluated in 90 fasting healthy subjects and 60 patients with food allergy by oral administration to both groups of 5 g of mannitol, a marker of absorption of small molecules, and 5 g of lactulose, a marker of abnormal absorption of large molecules, and subsequent measurement of urinary excretion of mannitol and lactulose. In healthy subjects, mean 5-hour urinary excretion of mannitol was 14.11% and of lactulose 0.26%. In the fasting state, the 60 patients with food allergy exhibited a mean urinary recovery of mannitol of 13.22%, not significantly different from that in healthy subjects. Mean recovery of lactulose in the patients with food allergy was 0.55%, significantly greater than in the healthy patients. After ingestion of food allergens by the patients, mean mannitol recovery fell to 11.57% and mean recovery of lactulose rose to 1.04%, both values being significantly different from those obtained in the fasting patients. On challenging the patients after they had taken sodium cromoglycate, mean mannitol and lactulose recoveries (13.53% and 0.62%, respectively) were not significantly different from those in fasting patients but were significantly different from those obtained on challenging patients unprotected by sodium cromoglycate. Evaluation of intestinal permeability in this way provides an objective means of diagnosing food allergy and assessing the effectiveness of anti-allergic agents such as sodium cromoglycate.

Cromolyn Sodium↗

[Lactulose-neomycin combination versus placebo in the treatment of acute hepatic encephalopathy. Results of a randomized controlled trial].

OBJECTIVES: The effectiveness of the association of lactulose with neomycin in the treatment of acute hepatic encephalopathy has never been assessed. The aim of this study was to compare the effects of lactulose-neomycin combination versus placebo in acute hepatic encephalopathy. METHODS: Eighty patients with cirrhosis were randomly treated for 5 days with placebo (n = 40) or with lactulose-neomycin (n = 40). Both groups were similar for all variables. RESULTS: The course of encephalopathy was similar in both groups. In the lactulose-neomycin group: 26 PATIENTS recovered, 3 remained unchanged, 3 worsened, 6 died, 2 were lost to follow-up. In the placebo group: 28 recovered, 2 remained unchanged, 2 worsened, 6 died, one was lost the follow-up, one dropped out of the study. Lactulose-neomycin treatment was not well tolerated in a significant number of patients. CONCLUSION: Lactulose-neomycin combination should not be used in the treatment of acute hepatic encephalopathy.

Acute Disease↗

Effect of acute lactulose administration on serum acetate levels in cirrhosis.

Lactulose has been used successfully in the treatment of portal-systemic encephalopathy but its exact mechanism of action is not known. The aim of this study was to observe the systemic effects of the colonic fermentation of an acute lactulose dose in cirrhotics and normal subjects. Six cirrhotic patients and 6 normal subjects were placed on 2 identical 2-d metabolic diets, 1 of which was supplemented with lactulose (1 g/100 kcals to a maximum of 28 g/d). Lactulose increased colonic fermentation in cirrhotic and normal subjects as evidenced by higher breath hydrogen and serum acetate levels. The increase in serum acetate levels after lactulose compared to control was similar in cirrhotic compared to normal subjects. However, the mean serum acetate concentration in the cirrhotics was significantly greater than that in the control subjects (p = 0.039), indicating increased endogenous production, or decreased peripheral utilization of acetate by the cirrhotic liver, or both. No change was observed in blood ammonia, glucose, insulin, or free fatty acid levels with lactulose.

Acetates↗

[Lactulose fermentation and lactose absorption in Chilean patients with liver cirrhosis: importance for hepatic encephalopathy therapy].

BACKGROUND: Non-absorbable carbohydrates are widely used in the therapy of hepatic encephalopathy. It has been argued that their effects depend on intestinal fermentation. In some geographic areas other than Chile up to 27% of healthy inhabitants are not able to increase breath hydrogen after a lactulose load, a parameter of intestinal fermentation of carbohydrate. Lactose has been proposed as an alternative to non-absorbable disaccharides in patients with lactase deficiency. AIM: To investigate intestinal fermentation of lactulose and lactose malabsorption in Chilean patients with liver cirrhosis. PATIENTS AND METHODS: 22 healthy controls and 52 patients with liver cirrhosis (16 with hepatic encephalopathy) were prospectively studied by means of lactulose or lactose hydrogen breath tests and lactose tolerance test. MAIN RESULTS: In the control group, 19% were non-hydrogen excretors after lactulose, meanwhile a significant rise in breath hydrogen concentration was observed in all cirrhotic patients (p < 0.01). Lactose tolerance test was indicative of lactase persistance in 37% of cirrhotics and in 43% of controls (NS). Finally, 41% of cirrhotics and 50% of controls had a normal lactose hydrogen breath test (NS). These results were not significantly modified by the presence of hepatic encephalopathy. CONCLUSION: Our data suggest that a lack in bacterial fermentation is not a cause of lactulose therapy failure in Chilean patients with hepatic encephalopathy. Lactose might be an inappropriate substitute to lactulose treating a significant proportion of patients with this condition in our country.

Adolescent↗

The role of lactulose in the prevention of bacterial translocation in surgical trauma.

Surgical trauma (ST) is one of the causative factor of bacterial translocation. In this study we investigated the prevention of bacterial translocation with lactulose in a surgical trauma model. The study was designed in 3 experimental groups consisting of 15 rats in each. Group 1 was sham operated controls, group 2 was ST + physiologic saline treated and group 3 was ST + lactulose treated animals. Lactulose and physiologic saline were given by oro-gastric intubation in a dose of 2 ml of 33.5% solution/d and 2 ml/d respectively starting 3 days prior to surgery. Bacterial translocation was investigated 48 hours after the operations. In sham operated controls only 1 bacterial translocation to the mesenteric lymph nodes (MLN) was observed. In the ST + physiologic saline treated group bacterial translocation to the MLN and portal venous blood (PVB) were significantly increased compared with both sham operated controls and the ST + lactulose treated group (p < 0.001). In rats with lactulose treatment the results of caecal bacterial counts showed a significant decrease in the number of gram-negative aerobes and facultative anaerobe bacteria (p < 0.01) and a significant increase in the number of lactobacilli (p < 0.001) compared to the sham operated controls. Measurement of the mucosal height showed a significant increase at the terminal ileum and the caecum compared with the sham operated controls and the surgical trauma+physiologic saline treated group (p < 0.001). We conclude that oral lactulose treatment 3 days prior to the surgical trauma, reduced the incidence of bacterial translocation to the MLN and PVB.

Animals↗

Proton MR spectroscopic measurement of neurometabolites in hepatic encephalopathy during oral lactulose therapy.

BACKGROUND AND PURPOSE: MR imaging and MR spectroscopy are increasingly being used to determine response to pharmacologic therapy. Hepatic encephalopathy (HE) is characterized by abnormal cerebral metabolites, yet the response to lactulose and other anti-HE measures is still primarily determined by using arbitrary categorical clinical rating scales, rather than MR spectroscopy. The purpose of this study was to determine whether MR spectroscopy could demonstrate relevant neurometabolic changes associated with lactulose therapy and thereby provide further support for the use of MR spectroscopy in clinical trials. METHODS: Ten control subjects and 23 patients with grades I to III HE were studied by proton MR spectroscopy with imaging parameters of 2000/26 (TR/TE). Metabolic ratios were calculated for myo-inositol (mI)/creatine (Cre), choline (Cho)/Cre, (glutamine + glutamate) (Glx)/Cre, N-acetylaspartate (NAA)/Cre, and (Cho + mI)/Glx. A time series design trial was used in which eight patients with HE were compared before and after lactulose therapy (60 mL by mouth three times per day). RESULTS: Relative to control subjects, HE was characterized by 43%, 64%, and 5% reductions, respectively, in mI/Cre, (Cho + mI)/Glx, and Cho/Cre. In comparison, Glx/Cre was increased by 75% and NAA/Cre was not changed. Therapy with lactulose was associated with increases of 29%, 37%, and 7%, respectively, in mI/Cre, (Cho + mI)/Glx, and Cho/Cre, as well as respective decreases of 15% and 42%, respectively, in Glx/Cre and HE grade. NAA/Cre did not change with lactulose therapy. CONCLUSION: MR spectroscopy detects neurometabolic changes associated with pharmacologic therapy for HE. The metabolic ratios ml/Cre and (Cho + mI)/Glx are the most sensitive measures of lactulose effect. These data support the expanded use of MR spectroscopy as an adjunctive technique in pharmaceutical development and clinical trials for HE.

Administration, Oral↗

A reference interval study of urinary lactulose excretion: a useful test of intestinal permeability in adults.

BACKGROUND/AIMS: Measurement of lactulose excretion in urine following oral ingestion is used as a noninvasive method of assessing small intestinal permeability. The aim of this study was to determine the adult reference interval of urinary lactulose excretion following oral administration. METHODS: Thirty seven volunteers (mean age 37.3 +/- 15 years) with no history of gastrointestinal disease were recruited as study subjects. All subjects were fasted overnight (10 hours), emptied their bladders and then drank a 50-mL solution containing 15 mL of Duphalac (10 g lactulose) and 35 mL flavoured water. Urine was collected for six hours in a bottle. Comparisons were made for 37 samples. RESULTS: In adults, the mean urinary lactulose concentration was 0.58 +/- 0.39 mmol/L. CONCLUSION: This study determined the adult reference range for lactulose excreted in the urine, using a sensitive quantitative assay based on hydrolysing lactulose and enzymatically assaying fructose, one of the component monosaccharides.

Journal Article↗

Increased concentrations of liver cholesterol in rats fed lactulose.

The disaccharide lactulose (beta-D-galactopyranosyl-(1-4)-D-fructofuranose) is thought to be poorly hydrolized by intestinal enzymes but is broken down by microorganisms in the colon. Thus lactulose shares with pectin similar characteristics. Lactulose is used in the food industry and in the treatment of constipation. There is preliminary evidence that dietary lactulose (5%, w/w) causes increased concentrations of serum and liver cholesterol in rats when compared with pectin. This paper describes dose-response relationships between dietary lactulose and cholesterol in either serum or liver.

Animals↗

Lactulose hydrogen breath test in orocecal transit assessment. Critical evaluation by means of scintigraphic method.

Orocecal transit time can be studied easily using the hydrogen breath test with lactulose, but the method has some important limitations. The orocecal transit time of 10 patients suffering from irritable bowel syndrome was measured twice, at a one-week interval, by breath test and scintigraphy simultaneously using an aqueous solution of 20 g lactulose containing 74 MBq of [99mTc]DTPA. Abdominal radioactivity and alveolar hydrogen values obtained every 5 min were noted and used to obtain the following: orocecal transit time by the two methods; ileocecal lactulose flow; total and per gram of lactulose hydrogen production; mean hydrogen concentration during the right colon filling; and measurement error of the breath test with respect to the scintigraphy. In the case of the breath test, the orocecal transit time intrapatient reproducibility was better (coefficient of variation = 13.5%) when a hydrogen threshold increment of 5 ppm was used; the best correlation with the scintigraphic measurement was observed at this threshold (r = 0.90, P < 0.001). The breath test overestimated orocecal transit time with the error correlating negatively and significantly with the total hydrogen production and, particularly, the mean hydrogen concentration (r = 0.79, P < 0.01): for a mean hydrogen concentration of more than 15 ppm, the error was negligible, while within this value there was a noticeable overestimation. To conclude, the lactulose hydrogen breath test is capable of giving an accurate measurement of orocecal transit time if a hydrogen threshold increment of 5 ppm is chosen and if the mean hydrogen concentration in the first 30 min of the right colon filling is taken into account.

Adult↗

Lactulose--a potential drug for the treatment of inflammatory bowel disease.

Lactulose is a drug mainly used as a laxative and for the treatment of porto-systemic encephalopathy. Following oral administration, intact lactulose reaches the colon, where it is split by bacteria, leading to a reduction in faecal pH and creating intestinal conditions beneficial to Lactobacillus acidophilus and inhibitory to coliform bacteria, bacteroides, Salmonella and Shigella. It was shown that lactulose therapy clears faecal salmonella and shigella species and reduces the prevalence of urinary-tract infection and respiratory tract infections. Oral administration of lactulose abolishes and prevents systemic endotoxemia of gut origin. Therefore lactulose may be used for treatment of inflammatory bowel disease as bacteria and bacterial endotoxin have an important role in the pathogenesis of this disease.

Bacteria↗

Simultaneous gas-chromatographic measurement of rhamnose, lactulose and sucrose and their application in the testing gastrointestinal permeability.

BACKGROUND: As it is important to test gastric and intestinal permeability simultaneously in gastrointestinal disorders such as Celiac disease, we developed a gas-chromatographic (GC) method to estimate rhamnose (L-rh), lactulose (Lacl) and sucrose (Suc) in urine. METHODS: The method is based on the use of alditol acetate derivatives giving a lower number of GC peaks than reducing sugars do. Acetate derivatives are more stable and less expensive than GC silylates and keep the flame-detector cleaner. We checked the chemical stability of alditol acetates by verifying the reproducibility of the standard curve of a sugar derivative sample which had been stored for 2 months at -20 degrees C. RESULTS: The calibration proved linear over the range 0.1-1 microg of sugar injected. Analytical sugar recovery was 88%+/-19.4% (mean+/-S.D.) for rhamnose, 105%+/-7.4% for sucrose and 102%+/-2.4% for lactulose. Mean within-day precision (CV) was 7.7% for rhamnose, 5.7% for sucrose and 1.9% for lactulose, and between-day (CV) was 6.7% for rhamnose, 3.9% for sucrose and 1.6% for lactulose. The rhamnose, lactulose and sucrose as the lactulose/rhamnose ratio clearly differentiated 25 healthy controls from 36 patients with active gluten-sensitive enteropathy. CONCLUSIONS: A fast, reliable and cheap gas-chromatographic method is presented here to evaluate gastric and intestinal permeability.

Celiac Disease↗

Correlation of intestinal lactulose permeability with exocrine pancreatic dysfunction.

Increased intestinal permeability to lactulose has been reported in patients with cystic fibrosis (CF). To determine whether this finding is unique to CF or whether it is related to accompanying exocrine pancreatic dysfunction, we evaluated 31 patients with CF and 10 with Shwachman syndrome who had variable degrees of pancreatic dysfunction, together with 17 healthy control subjects. There was no significant difference in the mean urinary lactulose excretion, expressed as the percentage of dose recovered, between CF and non-CF patients with pancreatic insufficiency (2.1% +/- 1.2% and 1.9% +/- 0.8, respectively) or between CF and non-CF patients with pancreatic sufficiency (0.6% +/- 0.5% and 0.6% +/- 0.3%, respectively). However, there was a significant difference in mean lactulose excretion between the pancreatic-insufficient and the pancreatic-sufficient patients (both CF and non-CF groups; p less than 0.001 and p less than 0.013, respectively). We further analyzed the results from 26 of the 41 patients (16 patients with CF and 10 non-CF patients) with pancreatic dysfunction who had previously undergone quantitative pancreatic function testing. A nonlinear, inverse relationship was found between urinary lactulose excretion and exocrine pancreatic function determined by duodenal trypsin output. These data confirm a direct relationship between intestinal lactulose permeability and the degree of exocrine pancreatic dysfunction, unrelated to the cause of the pancreatic disease.

Adolescent↗

Lactitol versus lactulose in the treatment of acute portal systemic encephalopathy (PSE). A controlled trial.

Preliminary data suggest that lactitol (beta-galactoside-sorbitol), a new synthetic non-absorbable disaccharide, has beneficial effects on chronic portal systemic encephalopathy. To compare the efficacy of lactitol vs. lactulose in the treatment of acute portal systemic encephalopathy (PSE), 40 cirrhotic patients with an acute episode of PSE were randomly allocated to one of two groups: group A (20 patients) received lactulose (30 ml/6 h) and group B (20 patients) lactitol (12 g/6 h). These doses were adjusted daily to obtain two bowel movements per day. The duration of treatment was 5 days. Age, sex, hepatic and renal function, precipitating factors and level of PSE measured by clinical examination, EEG and number connection test were similar in the two groups. A complete clinical resolution of PSE occurred in 11 patients in each group. In 5 patients of the lactulose group and in 6 of the lactitol group there was a moderate improvement of PSE during the study. Finally, 4 patients in the lactulose group and 3 in the lactitol group did not respond to treatment. No side effects attributable to therapy were observed in either group. These results indicate that lactitol is as effective as lactulose in the management of patients with cirrhosis and acute PSE.

Acute Disease↗

Porcine intestinal ammonia liberation. Influence of food intake, lactulose and neomycin treatment.

Lactulose and neomycin have, besides influencing ammonia production of the intestinal flora, been proposed to reduce glutamine-dependent ammonia formation. To test this hypothesis we determined the effects of lactulose and neomycin on the release or uptake of ammonia, urea, and amino acids across the intestine of freely moving healthy pigs. Blood was sampled from catheterized piglets (20 +/- 0.8 kg; n = 6) before and 1, 2, 3, and 6 h after a standard pig meal (750 g, 12% protein). After a week of lactulose (Legendal; 2 x 60 g/day) or neomycin (8 g/day) treatment this procedure was repeated. Electromagnetic portal and small bowel flow measurements were carried out in separate groups of pigs. Flow measurements were independent of the kind of food ingested. No significant alterations in flow could be detected during the 6 h study period. Portal and porto-arterial ammonia differences were significantly decreased after lactulose (-20%) and neomycin (-35%) treatment. alpha-Amino-nitrogen absorption decreased in both groups as compared to controls, but this decrease did not reach significance. Systemic and portal glutamine levels as well as intestinal glutamine utilization were significantly lower in the treatment groups. Citrulline and glutamate levels and intestinal production decreased after treatment. In this in vivo model, ammonia liberation after protein meals decreased in animals pretreated with lactulose or neomycin. The decreased systemic and consequently intestinal glutamine utilization may contribute to a reduction of endogenous ammonia formation in the gut wall. Diminished absorption from the gut of alpha-amino-nitrogen may, however, also contribute to a decrease in ammonia production.(ABSTRACT TRUNCATED AT 250 WORDS)

Alanine↗

The electroanalysis of mannitol, xylose and lactulose at copper electrodes: voltammetric studies and bioanalysis in human urine by means of HPLC with electrochemical detection.

The electrochemical behavior of mannitol, xylose and lactulose has been investigated at a copper working electrode. A sensitive, accurate and precise method employing HPLC with electrochemical detection in the d.c. amperometric mode, has been developed and validated for the determination of mannitol and lactulose in human urine. The ratio of these probe carbohydrates is altered in conditions that cause damage to the intestinal mucosal barrier. Systematic studies employing cyclic voltammetry indicate that the electrode reaction involves an electrocatalytic oxidation of each carbohydrate in a process yielding a single irreversible anodic wave that is dependent on the ionic strength of the sodium hydroxide supporting electrolyte solution. High performance liquid chromatography with electrochemical detection was performed using a thin-layer cell housing a custom manufactured copper working electrode. The optimized HPLC method can detect 72, 57 and 419 pg of mannitol, xylose and lactulose injected on column, respectively. The corresponding linear calibration ranges are 359 pg-2.24 microgram, 57.4 pg-896 ng and 419 pg-262 ng, respectively. Solid-phase extraction of human urine on polar sorbents, and direct injection after simple 1 + 99 dilution in 0.025 M NaOH were compared for bioanalysis. Direct injection was selected for further method developed as the technique proved robust and simple. The optimized method was validated for the determination of mannitol and lactulose in human urine over the concentration ranges predicted when assessing intestinal permeability (0.25-2.5 mg ml-1 mannitol and 0.05-1.0 mg ml-1 lactulose). Over these ranges intra- and inter-assay bias is < +/- 6.5%, and imprecision (coefficient of variation) is < 9% for each carbohydrate. The validated method provides a useful alternative to HPLC with pulsed-amperometric detection at gold electrodes.

Chromatography, High Pressure Liquid↗