Cyanides are highly toxic to all forms of life. The lethal dose for an adult human being is in the range of 100–150 mg [1-3]. Cyanides enter the environment through the synthesis of fertilizers, electroplating, metal cleaning, chemicals, plastics, resins, agriculture, cigarette smoke, and the combustion of coal [4-6]. If the environment is protected from pollution, the cyanide content of natural waters does not exceed 0.025 ppm [7]. The maximum recommended amount of cyanide in water by the WHO as CN- is 0.01 mg/l for humans and 0.03 mg/l for fish. Cyanides act directly on the nervous system and are readily absorbed through intact skin and by inhalation. The origin of blood cyanide concentrations may be from hydrocyanic acid inhalation from the combustion fumes of plastics [8,9]. Anoxia, headaches, enlargement of the thyroid glands, and convulsions with paralysis of the respiratory center in the brain are some of the symptoms associated with cyanide poisoning. The maximum tolerable concentration of cyanide is 5 mg/m3 in air [4,10]. Repeated exposure to small concentrations of cyanides over a long period causes paralysis of the legs and arms, loss of appetite, muscle cramps, psychoses, nausea, and weakness. Sodium hypochlorite has been widely used as a disinfectant for water and wastewater treatment [11,12]. Literature surveys revealed that cyanides form from the oxidation of amino acids by hypochlorite [13,14] and from the oxidation of Glycine pseudomonas species [15]. For these studies, I predict that the cyanide ion is formed by the reaction of some pharmaceuticals containing nitrogen with sodium hypochlorite. Pharmaceuticals are chemicals used for the diagnosis, cure, mitigation, or prevention of disease. Such drugs are used in large quantities in humans. Many studies have now been conducted that show that drugs and their metabolites are widely distributed in surface waters [16,17]. The aim of this work is to present the formation of cyanide ions by the reaction of some pharmaceuticals containing nitrogen with sodium hypochlorite on a laboratory scale.

Apparatus

A spectro-scan 50 uV visible spectrophotometer with 1.0 cm quartz cells was used.

Reagents

All chemicals used were of analytical or pharmaceutical grade, and the metformin hydrochloride, chlorhexidine gluconate, metronidazol, frusemide, trimethoprime, theophylline, and chloramphenicol standard materials were provided by the state company of drug industries and medical appliances (NDI) and al-Hokamaa (HPI) for the Pharmaceutical industry (Ninavah, Iraq).

Metformin hydrochloride solution (1x10^-3M)

This solution was prepared by dissolving 0.016 gm of metformin hydrochloride in 100 ml of distilled water in a volumetric flask.

Chlorhexidine gluconate solution (1x10^-3M)

This solution was prepared by diluting 0.45 mL of a 20% chlorhexidine gluconate solution with 100 mL of distilled water in a volumetric flask.

Metronidazol solution (1x10^-3M)

This solution was prepared by dissolving 0.017 gm of metronidazol in 100 ml of distilled water in a volumetric flask.

Frusemide solution (1x10^-3M)

This solution was prepared by dissolving 0.033 gm of frusemide in 100 ml of 0.01 N NaOH solution in a volumetric flask.

Trimethoprime solution (1x10^-3M)

This solution was prepared by dissolving 0.029 gm of trimethoprime in 100 ml of 0.01 N NaOH solution in a volumetric flask.

Theophylline solution (1x10^-3M)

This solution was prepared by dissolving 0.018 gm of theophylline in 100 ml of distilled water in a volumetric flask.

Chloramphenicol solution (1x10^-3M)

This solution was prepared by dissolving 0.032 gm of chloramphenicol in 100 ml of distilled water in a volumetric flask.

Cyanide stock solution (100 ppm)

This solution was prepared by dissolving 0.025 gm of KCN (BDH) in 100 ml of distilled water in a volumetric flask.

Cyanide working standard solution (1 ppm) (3.8 x 10^-3M)

This solution was prepared by diluting 1 ml of cyanide stock solution with 100 ml of distilled water in a volumetric flask.

Ninhydrine solution (1%)

Sodium carbonate solution (5%)

Sodium hypochlorite solution (5x10^-3M)

This solution was prepared by dilution of 0.5 ml of 8% sodium hypochlorite with 100 ml of distilled water, standardized every 4–5 days. This solution is stored in a dark bottle [18].

Sodium hydroxide solution (2.5N)

Recommended procedure [19]

An aliquot of cyanide standard solution containing (1.0–6.0 µg) of cyanide was transferred into a series of 25-ml volumetric flasks, to which 4 ml of 1% ninhydrin and 4 ml of 5% sodium carbonate were added. The solution was kept aside with occasional shaking for about 20 min for completion of the reaction to give a deep red color and diluted to the mark with 2.5 N sodium hydroxide. The deep blue color, which developed instantaneously, was stable for 30 minutes. The absorbance was measured at 590 nm against a reagent blank prepared in the same manner without cyanide, and a calibration graph was constructed.

Analysis of pharmaceuticals

To aliquot (50 ml) of each sample solution, including pharmaceuticals, add 50 ml of sodium hypochlorite solution. The solutions were kept aside for 20 minutes. Treat 2 ml of each solution as mentioned under the recommended procedure. The reagent blank was prepared in the same manner but contained no pharmaceuticals.

Analysis of a wastewater sample

The sample was collected from the effluents of the state company for drug industries and medical appliances in Mosul, Iraq. The sample was tested and found to be free of cyanide. An aliquot (50 ml) of wastewater sample was treated as mentioned under the analysis of pharmaceuticals.

The formation of cyanide ions by the reaction of pharmaceuticals containing nitrogen with sodium hypochlorite was examined using seven different compounds. These compounds were provided by the state company of drug industries and medical appliances (NDI) and al-Hokama for the pharmaceutical industry (HPI) (Nineveh, Iraq).

The formation of cyanide ions was observed in chlorhexidine gluconate, metronidazole, frusemide, and chloramphenicol. The largest formation was observed in chlorhexidine gluconate, and the lowest formation was observed in chloramphenicol.

Table 1: Formation of cyanide ions from pharmaceuticals by Sodium hypochlorite.

The reaction variables were optimized by varying each variable while keeping others constant to obtain maximum absorbance. The effect of pharmaceutical concentration (1x10^-3M) at a reaction time of 20 min. →The amount of cyanide ion formed to a maximum when the concentrations of sodium hypochlorite at 4-6x10^-3M and 5x10^-3M were used for subsequent experiments. Table 2 shows the effect of sodium hypochlorite on the formation of cyanide ions from chlorhexidine gluconate (1x10^-3M).

Table 2: Effect of Sodium hypochlorite NaOCl on the concentration of cyanide from chlorhexidine gluconate 1x10^-3M.

The effect of time on the formation of cyanide ion by the reaction of chlorhexidine gluconate (1x10^-3M) with 5x10^-3M sodium hypochlorite, increased to maximum at 15-45 min before decreasing and 20 min have been selected for subsequent experiment Table(3).

Table 3: Effect of reaction time on the formation of cyanide ion.

The mechanism of the formation of the cyanide ion was attributed to Norman and Dakin [15,16]. The first step was the formation of monochloramine, which, in excess of hypochlorite, converted to dichloramine as unstable and subsequently decomposed to cyanide, as shown below.

R-CH₂NH₂ + NaOCl → R-CH₂NHCl+NaOCl → R-CH₂NCl₂ →2HCN+RCl₂

Analytical application of the proposed method 

The proposed method has been successfully applied for the formation and determination of cyanide ions in environmental wastewater samples collected from the effluent of the state company of drug industries and medical appliances (NDI) (Ninavah, Iraq). The results are given in Table 4.

Table 4: Formation of cyanide ions from wastewater by NaOCL.

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