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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 major degradation product of methylnicotinate was nicotinic acid which formed at an approximate rate of 0.5% of the starting methylnicotinate concentration per annum.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

Lack of effect of storage time upon extent of erythema induced by methylnicotinate. 10 mM aqueous solutions of methylnicotinate prepared from stock solutions which had been stored for various lengths of time at 4°C were applied to the forearm of 8 healthy volunteers and the induced erythema assessed visually at 5, 10 and 15 minutes post-application using a 4-point scale. Values shown are mean erythema; bars indicate the standard deviation.
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Figure 3: Lack of effect of storage time upon extent of erythema induced by methylnicotinate. 10 mM aqueous solutions of methylnicotinate prepared from stock solutions which had been stored for various lengths of time at 4°C were applied to the forearm of 8 healthy volunteers and the induced erythema assessed visually at 5, 10 and 15 minutes post-application using a 4-point scale. Values shown are mean erythema; bars indicate the standard deviation.

Mentions: In addition to the HPLC analysis, the vasodilatatory activity of aged solutions was also investigated. The four batches utilised had been stored for 0, 320, 725 and 1057 days respectively at the time of testing. The 1 M stock solutions were diluted to 10 mM and 1 cm2 paper patches were impregnated with approximately 30 μl of the solution as previously described in detail [4]. The patches were applied to the forearms of eight healthy volunteers (4 male, 4 female, age was 44 ± 12 years [mean ± SD]. The area of skin to which the patch was applied was examined for, and was free of, damage. The skin patch procedure had been reviewed and approved by NHS Highlands Research Ethics Committee. All subjects gave informed consent including that the data obtained from their participation may be published in aggregate format. Erythema, monitored at 5, 10 and 15 minutes after application, was assessed visually using a 4 point scale (0 – no erythema, 1 – perceptible but slight erythema, 2 – moderate erythema, 3 – pronounced erythema). As illustrated in Figure 3, the batch age had no effect upon the extent of erythema (2-way ANOVA with factors time and batch age). There was no statistically significant interaction between time and batch age (F6,56 = 0.21; P > 0.9) nor was their a significant effect of batch age (F3,56 = 0.16; P > 0.9), although there was a statistically significant effect of time (F2,56 = 175.34; P < 0.0001)). The testing of the ability of each batch of methylnicotinate to induce erythema was performed using a single dose. We cannot rule out that an effect of batch age would have been observed using different, especially lower, concentrations, although we consider such a possibility unlikely. It has been reported that methylnicotinate-induced erythema is reduced with age [19]. We did not observe, however, a statistically significant correlation between age and erythema (for example the Pearson correlation coefficient between erythema at 15 minutes and subject age was – 0.31; P < 0.05), although the small sample size may have prevented us from detecting such a relationship.


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

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

Lack of effect of storage time upon extent of erythema induced by methylnicotinate. 10 mM aqueous solutions of methylnicotinate prepared from stock solutions which had been stored for various lengths of time at 4°C were applied to the forearm of 8 healthy volunteers and the induced erythema assessed visually at 5, 10 and 15 minutes post-application using a 4-point scale. Values shown are mean erythema; bars indicate the standard deviation.
© Copyright Policy - open-access
Related In: Results  -  Collection

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Figure 3: Lack of effect of storage time upon extent of erythema induced by methylnicotinate. 10 mM aqueous solutions of methylnicotinate prepared from stock solutions which had been stored for various lengths of time at 4°C were applied to the forearm of 8 healthy volunteers and the induced erythema assessed visually at 5, 10 and 15 minutes post-application using a 4-point scale. Values shown are mean erythema; bars indicate the standard deviation.
Mentions: In addition to the HPLC analysis, the vasodilatatory activity of aged solutions was also investigated. The four batches utilised had been stored for 0, 320, 725 and 1057 days respectively at the time of testing. The 1 M stock solutions were diluted to 10 mM and 1 cm2 paper patches were impregnated with approximately 30 μl of the solution as previously described in detail [4]. The patches were applied to the forearms of eight healthy volunteers (4 male, 4 female, age was 44 ± 12 years [mean ± SD]. The area of skin to which the patch was applied was examined for, and was free of, damage. The skin patch procedure had been reviewed and approved by NHS Highlands Research Ethics Committee. All subjects gave informed consent including that the data obtained from their participation may be published in aggregate format. Erythema, monitored at 5, 10 and 15 minutes after application, was assessed visually using a 4 point scale (0 – no erythema, 1 – perceptible but slight erythema, 2 – moderate erythema, 3 – pronounced erythema). As illustrated in Figure 3, the batch age had no effect upon the extent of erythema (2-way ANOVA with factors time and batch age). There was no statistically significant interaction between time and batch age (F6,56 = 0.21; P > 0.9) nor was their a significant effect of batch age (F3,56 = 0.16; P > 0.9), although there was a statistically significant effect of time (F2,56 = 175.34; P < 0.0001)). The testing of the ability of each batch of methylnicotinate to induce erythema was performed using a single dose. We cannot rule out that an effect of batch age would have been observed using different, especially lower, concentrations, although we consider such a possibility unlikely. It has been reported that methylnicotinate-induced erythema is reduced with age [19]. We did not observe, however, a statistically significant correlation between age and erythema (for example the Pearson correlation coefficient between erythema at 15 minutes and subject age was – 0.31; P < 0.05), although the small sample size may have prevented us from detecting such a relationship.

Bottom Line: 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.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