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Stability of methylnicotinate in aqueous solution as utilized in the 'niacin patch test'.

Ross BM, Katzman M - BMC Res Notes (2008)

Bottom Line: The topical application of methylnicotinate results in a localized vasodilatatory response which has been found to differ from that observed to occur in healthy controls in a variety of medical conditions.No significant difference in vasodilatatory response was apparent between batches which had been stored for between zero and 1057 days.Methylnicotinate exhibits excellent chemical and biological stability in solution facilitating its use in clinical applications.

View Article: PubMed Central - HTML - PubMed

Affiliation: Northern Ontario School of Medicine, Lakehead University, Thunder Bay, Ontario, Canada. brian.ross@normed.ca

ABSTRACT

Background: The topical application of methylnicotinate results in a localized vasodilatatory response which has been found to differ from that observed to occur in healthy controls in a variety of medical conditions. The stability of the drug in aqueous solution is unclear while difficulties can be encountered when preparing methylnicotinate solutions for this purpose. To aid in the determination of how long solutions of the drug should be stored before discarding we have used a collection of aged batches of methylnicotinate to determine the stability of the drug in aqueous solution.

Findings: The degradation of methylnicotinate was determined in batches which had been stored at 4 degrees C for between 5 and 1062 days prior to analysis by High Performance Liquid Chromatography. The major degradation product of methylnicotinate was nicotinic acid which formed at an approximate rate of 0.5% of the starting methylnicotinate concentration per annum. Furthermore, the ability of methylnicotinate solutions of different ages to induce vasodilatation was assessed in healthy volunteers. No significant difference in vasodilatatory response was apparent between batches which had been stored for between zero and 1057 days.

Conclusion: Methylnicotinate exhibits excellent chemical and biological stability in solution facilitating its use in clinical applications.

No MeSH data available.


Related in: MedlinePlus

Relationship between batch age, methylnicotinate concentration and relative nicotinic acid content of 1 M aqueous solutions of methylnicotinate. Batches of 1 M methylnicotinate were stored at 4°C for increasing lengths of time prior to analysis by HPLC. Filled circles, plotted on the right axis, show the measured concentration of methylnicotinate in each batch. Open circles, plotted on the left axis, show the percentage of nicotinic acid relative to the total methylnicotinate plus nicotinic acid concentration in each batch. Values shown are the mean of quadruplicate determinations; bars indicate the standard deviation. The 'best-fit' linear regression line for the correlation between batch age and nicotinic acid content is indicated by a solid line; the dotted lines indicate the 95% confidence intervals for this line based on the available data.
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Figure 1: Relationship between batch age, methylnicotinate concentration and relative nicotinic acid content of 1 M aqueous solutions of methylnicotinate. Batches of 1 M methylnicotinate were stored at 4°C for increasing lengths of time prior to analysis by HPLC. Filled circles, plotted on the right axis, show the measured concentration of methylnicotinate in each batch. Open circles, plotted on the left axis, show the percentage of nicotinic acid relative to the total methylnicotinate plus nicotinic acid concentration in each batch. Values shown are the mean of quadruplicate determinations; bars indicate the standard deviation. The 'best-fit' linear regression line for the correlation between batch age and nicotinic acid content is indicated by a solid line; the dotted lines indicate the 95% confidence intervals for this line based on the available data.

Mentions: The concentration of methylnicotinate in each batch did not differ significantly between batches of different ages, all having the expected measured concentration of approximately 1 M (Figure 1), and there was no significant linear relationship with batch age (Pearson correlation coefficient was 0.001; P > 0.05). Qualitative assessment of the chromatograms of freshly prepared methylnicotinate indicated that apart from the compound itself, the predominant contaminant co-eluted with nicotinic acid. Representative chromatograms are shown in Figure 2. The concentration of nicotinic acid in a batch of methylnicotinate prepared 5 days previously was 0.060 ± 0.002% (mean ± SD nicotinate as a percentage of methylnicotinate analysed in quadruplicate). As illustrated in Figure 1 the degradation of methylnicotinate to form nicotinic acid proceeded linearly with respect to time (Pearson correlation coefficient = 0.98) at a rate of 0.00150% per day (95% confidence interval was 0.001270% to 0.00172%) or 0.54% per 365 day year (95% confidence interval was 0.47% to 0.63%).


Stability of methylnicotinate in aqueous solution as utilized in the 'niacin patch test'.

Ross BM, Katzman M - BMC Res Notes (2008)

Relationship between batch age, methylnicotinate concentration and relative nicotinic acid content of 1 M aqueous solutions of methylnicotinate. Batches of 1 M methylnicotinate were stored at 4°C for increasing lengths of time prior to analysis by HPLC. Filled circles, plotted on the right axis, show the measured concentration of methylnicotinate in each batch. Open circles, plotted on the left axis, show the percentage of nicotinic acid relative to the total methylnicotinate plus nicotinic acid concentration in each batch. Values shown are the mean of quadruplicate determinations; bars indicate the standard deviation. The 'best-fit' linear regression line for the correlation between batch age and nicotinic acid content is indicated by a solid line; the dotted lines indicate the 95% confidence intervals for this line based on the available data.
© Copyright Policy - open-access
Related In: Results  -  Collection

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Figure 1: Relationship between batch age, methylnicotinate concentration and relative nicotinic acid content of 1 M aqueous solutions of methylnicotinate. Batches of 1 M methylnicotinate were stored at 4°C for increasing lengths of time prior to analysis by HPLC. Filled circles, plotted on the right axis, show the measured concentration of methylnicotinate in each batch. Open circles, plotted on the left axis, show the percentage of nicotinic acid relative to the total methylnicotinate plus nicotinic acid concentration in each batch. Values shown are the mean of quadruplicate determinations; bars indicate the standard deviation. The 'best-fit' linear regression line for the correlation between batch age and nicotinic acid content is indicated by a solid line; the dotted lines indicate the 95% confidence intervals for this line based on the available data.
Mentions: The concentration of methylnicotinate in each batch did not differ significantly between batches of different ages, all having the expected measured concentration of approximately 1 M (Figure 1), and there was no significant linear relationship with batch age (Pearson correlation coefficient was 0.001; P > 0.05). Qualitative assessment of the chromatograms of freshly prepared methylnicotinate indicated that apart from the compound itself, the predominant contaminant co-eluted with nicotinic acid. Representative chromatograms are shown in Figure 2. The concentration of nicotinic acid in a batch of methylnicotinate prepared 5 days previously was 0.060 ± 0.002% (mean ± SD nicotinate as a percentage of methylnicotinate analysed in quadruplicate). As illustrated in Figure 1 the degradation of methylnicotinate to form nicotinic acid proceeded linearly with respect to time (Pearson correlation coefficient = 0.98) at a rate of 0.00150% per day (95% confidence interval was 0.001270% to 0.00172%) or 0.54% per 365 day year (95% confidence interval was 0.47% to 0.63%).

Bottom Line: The topical application of methylnicotinate results in a localized vasodilatatory response which has been found to differ from that observed to occur in healthy controls in a variety of medical conditions.No significant difference in vasodilatatory response was apparent between batches which had been stored for between zero and 1057 days.Methylnicotinate exhibits excellent chemical and biological stability in solution facilitating its use in clinical applications.

View Article: PubMed Central - HTML - PubMed

Affiliation: Northern Ontario School of Medicine, Lakehead University, Thunder Bay, Ontario, Canada. brian.ross@normed.ca

ABSTRACT

Background: The topical application of methylnicotinate results in a localized vasodilatatory response which has been found to differ from that observed to occur in healthy controls in a variety of medical conditions. The stability of the drug in aqueous solution is unclear while difficulties can be encountered when preparing methylnicotinate solutions for this purpose. To aid in the determination of how long solutions of the drug should be stored before discarding we have used a collection of aged batches of methylnicotinate to determine the stability of the drug in aqueous solution.

Findings: The degradation of methylnicotinate was determined in batches which had been stored at 4 degrees C for between 5 and 1062 days prior to analysis by High Performance Liquid Chromatography. The major degradation product of methylnicotinate was nicotinic acid which formed at an approximate rate of 0.5% of the starting methylnicotinate concentration per annum. Furthermore, the ability of methylnicotinate solutions of different ages to induce vasodilatation was assessed in healthy volunteers. No significant difference in vasodilatatory response was apparent between batches which had been stored for between zero and 1057 days.

Conclusion: Methylnicotinate exhibits excellent chemical and biological stability in solution facilitating its use in clinical applications.

No MeSH data available.


Related in: MedlinePlus