Measurement ofN-methyl-2-pyridone-5-carboxamide in urine by high performance liquid chromatography

Moore, W.; Bolton, Christopher; Downs, L. G.; Gilmor, Hilary A.; Gale, E. A. M.

doi:10.1002/(sici)1099-0801(200004)14:2<69::aid-bmc922>3.0.co;2-n

Cited by 9 publications

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References 10 publications

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“…Nicotinamide is water-soluble, and readily absorbed by mouth. Pharmacokinetic studies carried out by our group have shown that human metabolism is predominantly by methylation to N-methyl-2-pyridone-5-carboxamide, in which form it is excreted in the urine; oxidation to nicotinamide oxide also occurs, but there is no direct conversion to nicotinic acid [27,28]. At high doses, such as those used in ENDIT, peak levels of nicotinamide of 0.3-1.0 mmol/l are seen in the circulation; the 50% inhibition concentration of nicotinamide for PARP is about 0.1 mmol/l [29].…”

Section: Discussionmentioning

confidence: 99%

Intervening before the onset of Type 1 diabetes: baseline data from the European Nicotinamide Diabetes Intervention Trial (ENDIT)

Gale

Inte²

2003

Diabetologia

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Aims/hypothesis To set up a clinical trial to establish whether nicotinamide can prevent or delay clinical onset of Type 1 diabetes.Method The European Nicotinamide Diabetes Intervention Trial is a randomised, double-blind, placebo-controlled intervention trial undertaken in 18 European countries, Canada and the USA.Entry criteria were a first-degree family history of Type 1 diabetes, age 3-40 years, confirmed islet cell antibody (ICA) levels greater than or equal to 20 JDF units, and a non-diabetic OGTT; the study group was further characterised by intravenous glucose tolerance testing, measurement of antibodies to GAD, IA-2 and insulin and HLA class II genotyping.Results ICA screening was carried out in approximately 30,000 first-degree relatives. A total of 1004 individuals fulfilled ICA criteria for eligibility, and 552 (288 male) were randomised to treatment. Of these, 331 were aged less than 20 years (87% siblings and 13% offspring of the proband with diabetes) and 221 were 20 years of age or more (76% parents, 21% siblings and 3% offspring). Oral glucose tolerance was normal in 500 and impaired in 52 (9.4%), and first phase 1 insulin response in the IVGTT was below the 10 th centile in 34%. Additional islet autoantibodies were identified in 354 trial entrants. Diabetes-associated HLA class II haplotypes were found in 84% of the younger age group and 80% of the older group. The protective haplotype HLA-DQA1*0102-DQB1*0602 was found in 10% overall.Conclusions/interpretation ENDIT has shown that a trial of an intervention designed to halt or delay progression to Type 1 diabetes can be carried out on a multinational collaborative basis, as and when potentially safe and effective forms of intervention become available. Primary screening with biochemically defined autoantibodies will substantially reduce the number of lower risk individuals to be included in future intervention trials Europe includes countries with the highest incidence of Type 1 (insulin-dependent) diabetes mellitus in the world. These rates continue to rise rapidly, and the EURODIAB TIGER Concerted Action has shown an annual 3 to 4% increase in the incidence of childhood diabetes across our continent [1]. In Finland, it is estimated that childhood diabetes is now four times as common as 2 it was in the 1950s [2]. There is currently no means of preventing or curing this disorder. Type 1 diabetes can, however, be predicted by screening for islet autoantibodies, and both animal and human pilot studies suggest that prevention is possible. The US Diabetes Prevention Trial-Type 1 (DPT-1) has recently reported experience with parenteral insulin therapy in high risk relatives of an individual with Type 1 diabetes [3]. Here we show baseline data from a trial of high-dose oral nicotinamide, and demonstrate that a candidate preventive measure can be tested successfully on a multinational collaborative basis. MethodsStudy Design ENDIT is a randomised, double-blind, placebo controlled trial designed to test whether daily oral administration of hi...

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Section: Discussionmentioning

confidence: 99%

Intervening before the onset of Type 1 diabetes: baseline data from the European Nicotinamide Diabetes Intervention Trial (ENDIT)

Gale

Inte²

2003

Diabetologia

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“…The majority use a prior purification step, with an anion exchange resin [12], a mixture of anion and cation exchange resins [13], reversed phase extraction [14] or solvent extraction [15,16]. Analysis has also been performed following enzymatic treatment [17] and with no prior purification [18,19].…”

Section: Hplc Analysis Of 2-pyr and 1-mn In Urinementioning

confidence: 99%

Quantitation of the niacin metabolites 1-methylnicotinamide and l-methyl-2-pyridone-5-carboxamide in random spot urine samples, by ion-pairing reverse-phase HPLC with UV detection, and the implications for the use of spot urine samples in the assessment of niacin status

Creeke

Seal

2005

Journal of Chromatography B

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Determination of amobarbital and secobarbital in plasma samples using micellar liquid chromatography

Quiñones-Torrelo

Martı́n-Biosca

Sagrado

et al. 2000

Biomed. Chromatogr.

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A new liquid chromatographic procedure for the determination of amobarbital and secobarbital in plasma samples is proposed. The method uses a Spherisorb octadecylsilane ODS-2 C(18) analytical column, a guard column of similar characteristics and 0.04 M CTAB solution buffered at pH 7.5 containing 3% 1-propanol as micellar mobile phase. The UV detection was carried out at 250 nm. Butabarbital was used as internal standard. Plasma samples preparation only required adequate dilution with the mobile phase before injection into the chromatographic system. The limits of detection were 0.2 and 0.4 mg/L for amobarbital and secobarbital, respectively. The proposed method allows the determination of amobarbital and secobarbital in plasma at therapeutic levels.

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Measurement ofN-methyl-2-pyridone-5-carboxamide in urine by high performance liquid chromatography

Cited by 9 publications

References 10 publications

Intervening before the onset of Type 1 diabetes: baseline data from the European Nicotinamide Diabetes Intervention Trial (ENDIT)

Intervening before the onset of Type 1 diabetes: baseline data from the European Nicotinamide Diabetes Intervention Trial (ENDIT)

Quantitation of the niacin metabolites 1-methylnicotinamide and l-methyl-2-pyridone-5-carboxamide in random spot urine samples, by ion-pairing reverse-phase HPLC with UV detection, and the implications for the use of spot urine samples in the assessment of niacin status

Determination of amobarbital and secobarbital in plasma samples using micellar liquid chromatography

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