Stability Of Sodium Nitroprusside In Aqueous Solutions

Introduction

Sodium nitroprusside (SNP) is red-brown odorless crystal, stable in air but photosensitive so it should be protected from light, also small amount of moisture with light is enough to photodegrade sodium nitroprusside. Beside the photodegradation, sodium nitroprusside undergoes many reactions which some of them are undefined, or it yields Prussian blue, cyanic acid and nitric oxide [1,2]. Sodium nitroprusside is a strong, rapidly acting hypotensive agent in the emergencies, heart failure and for controlled hypotension during surgery. It is delivered by vain injection. The efficiency of this drug is probably due to the release of radical nitric oxide (NO˙) or the S-nitroso compounds [3]. It has two main limitations: biologically the toxic effect linked with the production of cyanide ions, analytically: the stability in aqueous solution. To overcome these limitations, studying the stability in aqueous solutions and developing a system to keep the material stable without any releasing of toxic side product have attracted the scientist.

Spectrophotometric methods, HPLC and polarographic methods were used to study the stability of sodium nitroprusside. This report is summarizing and comparing the methods developed and the results of the stability studies, that might help in proposing more suitable way to reach better stability of sodium nitroprusside in aqueous medium.

Stability study using spectrophotometric methods:

Spectrophotometric methods were used in many studies to determine the stability of sodium nitroprusside, by measuring the released amount of cyanide ions or ferricyanide ions in case of any decomposition happened for sodium nitroprusside sample. The decomposition of SNP is expressed as the following reactions:

• [FeIV(CN)5NO]2- + H2O [FeIII(CN)5H2O]2- + NO
• [FeIII(CN)5H2O]2- 5CN- + decomposition products
• [FeIII(CN)5H2O]2- + 5CN- 5 [FeIII(CN)6]3- + 5 H2O

Sodium nitroprusside is usually kept in 5% dextrose infusion solution when used in surgeries. A study was done by Vesey and Batistoni [4] to develop a spectrophotometric method using colorimetric procedure, as the amount of SNP in the infusion sample is very low (50-200µg.mL-1) which make the absorbance detection of these solution very hard. Adding SNP to sulphide solution at pH 12 and above produce red-purple color, which is detected at 540 nm. It is important to cover the sample container with foil to protect the sample from any photodecomposition.

The solution preparation methods are stated in the paper [4], the study was conducted in different types of light sources, (a) daylight, (b) tungsten light and (c) fluorescent light, and in different solutions which are 5% dextrose, saline and water.

The results of this study were as following:

The concentration of SNP of the sample exposed to daylight decreased to 50% in two days, and it was accompanied by a rise in the free cyanide ions. In the artificial light the decomposition was less and slower, after 50 h exposure the decomposition of SNP was around 20%, and the released cyanide ions concentration in the sample exposed to fluorescence light was half the concentration of the sample exposed to tungsten. The results were collected using spectrophotometric absorbance at 394 nm. In this study also the appearance of blue color (Prussian blue) after the decomposition of SNP was observed in the dextrose solution while in saline solution the color changed to green blue. But the preferred solution to be used in preparing the infusion solution is dextrose. Keeping the SNP in water at room temperature or at 4°C was observed for two years and found to be stable without any decomposition as long it is covered and kept preserved from light. Figure (1) is showing the data related

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• i. Plot of percentage decrease in SNP concentration against absorbance at 394 nm measured at 30 min intervals during exposure.
• ii. Percentage decrease in SNP concentration with time of exposure.
• iii. Change in absorbance at 394 nm with time of exposure. • dextrose solution of SNP, o saline solution. The arrow shows point at which the dextrose solution began to turn blue. Adapted from [4] Vesey, C., & Batistoni, G. (1977). The determination and stability of sofium nitroprusside in aqueous solutions (determination and stability of SNP). Journal of Clinical Pharmacy and Therapeutics, 2(2), 105–117.

Another study was done by Bisset et al. [5] where they also studied the decomposition of SNP depending on the cyanide released using cyanide ion-selective electrode. This study was conducted in blood, plasma and washed electrolytes. First the mediums used to detect the cyanide ions were taken as it is without any controlling for the pH, but all the solutions were covered with foil to avoid any light exposure. Also, color test was conducted using pyrazolone color reagent to check qualitatively for any decomposition in the sample. The color test for the normal solution was negative indicating no decomposition observed in this case, also the ion selective electrode didn’t detect any cyanide ion in all the samples when SNP was added and were covered from light. When the solutions were acidified to pH 4, and in the presence of light, SNP decomposed almost completely (99.5%) over the period of 2 h. but the decomposition was neglected in the dark even when acidified. Blood, plasma and washed electrolytes don’t have any effect on the decomposition of SNP.

Keeping the SNP solution isolated from light is not applicable while passing though the burette or in the tubing of the infusion set, so another study was proposed to check the stability of SNP in the presence of light by monitoring the cyanide ions using continuous-flow method and ferricyanide ions using spectrophotometric method, as ion selective electrode is not convenient to use because it need to adjust the pH to 12 while the study is conducted in acidic pH [6]. These two methods were used to get the calibration curves of these ions to help in determining the decomposition percentage of SNP. Chloramine T-barbituric acid reaction was used for cyanide detection to generate cyanogen chloride to produce chromophore so it could be detected spectrophotometry at 580 nm, this reaction was described by Blanke. For ferricyanide detection was achieved by adding FeSO4. 7H2O in 1% H2SO4 to produce Prussian blue which is monitored spectrophotometrically at 750 nm. Figure (2) is schematic representation for the continuous flow apparatus. To promote the photodecomposition, UV light with 366 nm intensity was used. In cyanide ions standards which were prepared in aqueous and glucose solutions, it was observed that cyanide is reacting with the carbon atom of the aldehyde group in glucose which caused a decay in the cyanide concentrations. This was not observed in the standards kept in the aqueous solution. The result of this methods was that 24% of SNP have decomposed after monitoring it for 140 minutes under UV light exposure. Comment by fatima abla: Add reference or not?

For the study of ferricyanide ion in which the standard results were identical in both aqueous and glucose solutions, it is found to be alternative of the cyanide ions study. The ferrous ion with the ferricyanide reaction is a known as qualitative test, but in this study, it was developed to be quantitative test. The result of this method that the production of ferricyanide ions started after 40 minutes from exposing the SNP sample to UV at intensity of 366 nm. The decomposition percentage was around 20 after 240 minutes which is close to the cyanide result, and these results are based on the amount of SNP in the clinical usage.

Stability study using HPLC

High-performance-liquid chromatography is considered an effective method in studying the stability of SNP. Baaske et al. [7] investigated the stability of SNP using ion-pair reversed-phase HPLC with UV detection for rapid direct measurement of SNP or intravenous solutions. The standards stock and the samples studied were covered in foil to be protected from light. The study included changing in the pH of the solutions from acidic to basic, the first to be eluted was the photodegradation products then ferrocyanide then ferricyanide and finally the nitroprusside. As the pH increased the retention time for the studied materials increased as shown in figure (3).

The greatest separation was found to b at pH= 7.1 so this pH was chosen in this study, the admixture of SNP prepared to study the stability was kept protected from light and covered with foil, when it was injected to the chromatography system not evidence of any degradation of SNP or even adsorption. Another sample was exposed to normal light when used in the infusion and monitored in HPLC, it was found that small amount of the sample was degraded from light not from adsorption cause. Even the degradation was small around 3.5% but it still considered as evidence for photodegradation of the sample during the infusion. This was done over 300 minutes.

A photodegradation study was also conducted in presence of direct sunlight, normal fluorescent light and laboratory room light, the stability of SNP was observed at laboratory room light and the normal fluorescent light for first few hours, after six hours the decomposition was 7%. But still recommendation for covering the sample with foil and protect it from light is needed as the photodegradation products considered toxic materials. When the sample was exposed to direct sunlight the remaining SNP in the sample is around 32% in one hour only.

This result was contradicted by a study done after two years by Mahoony et al. [8] in various intravenous solutions during the infusions also on the type of the container (glass or plastic). The solutions that were chosen are: 5% dextrose, normal saline and lactated Ringer’s solutions in glass and plastic container, covered with foil and then exposed to light. The results of the samples kept in both glass and plastic containers did not decomposed and were stable for 48 h if they are not exposed directly to light, and the type of solution are not affecting or decomposing SNP. Also, these sample were traversing through plastic infusion set for 24 and 8 h, respectively, to check the exposure to light during this infusion in surgeries if it would affect SNP and release any decomposition product or not, and the result was that the sample is stable and doesn’t undergo any decomposition in these solutions

References

1. Rucki, R. (1977). Sodium Nitroprusside. Analytical Profiles of Drug Substances, 487–513.
2. Frank, M., Johnson, J., & Rubin, S. (1976). Spectrophotometric Determination of Sodium Nitroprusside and its Photodegradation Products. Journal of Pharmaceutical Sciences, 65(1), 44–48.
3. Tsikas, D., Böger, R. H., Bode-Böger, S. M., Brunner, G., & Frölich, J. C. (1995). Formation of S-nitroso compounds from sodium nitroprusside, nitric oxide or nitrite and reduced thiols: analysis by capillary isotachophoresis. Journal of Chromatography A, 699(1-2), 363–369.
4. Vesey, C., & Batistoni, G. (1977). The determination and stability of sofium nitroprusside in aqueous solutions (determination and stability of SNP). Journal of Clinical Pharmacy and Therapeutics, 2(2), 105–117.
5. Bisset, W., Butler, A., Glidewell, C., & Reglinski, J. (1981). Sodium Nitroprusside and Cyanide Release: Reasons for Re-Appraisal. British Journal of Anaesthesia, 53(10), 1015–1018.
6. Hartley, T., Philcox, J., & Willoughby, J. (1985). Two Methods for Monitoring the Photodecomposition of Sodium Nitroprusside in Aqueous and Glucose Solutions. Journal of Pharmaceutical Sciences, 74(6), 668–671.
7. Baaske, D. M., Smith, M. D., Karnatz, N., & Carter, J. E. (1981). High-performance liquid chromatographic determination of sodium nitroprusside. Journal of Chromatography A, 212(3), 339–346.
8. Mahony, C., Brown, J. E., Stargel, W. W., Verghese, C. P., & Bjornsson, T. D. (1984). In Vitro Stability of Sodium Nitroprusside Solutions for Intravenous Administration. Journal of Pharmaceutical Sciences, 73(6), 838–839.