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N Acetylcysteine Quality Control

N-acetylcysteine (C5H9NO3S Mr 163.2) is the N-acetyl derivative of the naturally occurring amino acid, l-cysteine. The drug occurs as a white, crystalline powder with a slight acetic odor. N-acetylcysteine is freely soluble in water and in alcohol. N-acetylcysteine is commercially available as aqueous solutions of the sodium salt of the drug. It is used as a mucolytic or as an antidote for paracetamol. The British Pharmacopoeia contains a number of tests for this compound designed to ensure the quality.
N-acetylcysteine acts to reduce mucus viscosity by splitting disulfide bonds linking proteins present in the mucus (mucoproteins). Inhaled N-acetylcysteine is indicated for mucolytic (“mucus-dissolving”) therapy as an adjuvant in respiratory conditions with excessive and/or thick mucus production. Such conditions include emphysema, bronchitis, tuberculosis, bronchiectasis, amyloidosis, pneumonia. It is also used post-operatively, as a diagnostic aid, and in tracheostomy care. It may be considered ineffective in cystic fibrosis (Rossi, 2006). However, a recent paper in the Proceedings of the National Academy of Sciences reports that high-dose oral N-acetylcysteine modulates inflammation in cystic fibrosis and has the potential to counter the intertwined redox and inflammatory imbalances in CF (Tirouvanziam et al., 2006). Oral N-acetylcysteine may also be used as a mucolytic in less serious cases.
N-acetylcysteine also acts to augment glutathione reserves (depleted by toxic paracetamol metabolites) in the body and, together with glutathione to directly bind to toxic metabolites. These actions serve to protect hepatocytes in the liver from toxicity due to paracetamol overdose. Intravenous N-acetylcysteine is indicated for the treatment of paracetamol (acetaminophen) overdose. Oral N-acetylcysteine for this indication is uncommon as it is poorly tolerated owing to the high doses required (due to poor oral bioavailability), unpleasant taste or odour and adverse drug reactions (particularly nausea and vomiting). However, some people have shown an adverse allergy to intravenous N-acetylcysteine which includes extreme breathing difficulty, light-headedness, rashes, severe coughing and sometimes also vomiting. Repeated overdoses will cause the allergic reaction to get worse and worse.
N-acetylcysteine is prone to both hydrolysis and oxidation and some of the impurities from these reactions are shown below.
Scheme 2
2. Experimental: 2.1. Materials:
The materials used in this experiment were N-acetylcysteine powder, disodium edentate solution, 1M sodium hydroxide and mixed phosphate buffer pH 7.0, water, dilute hydrochloric acid, potassium iodine solution, 0.05M iodine, 0.1M sodium hydroxide, starch, phenol red and phenolphthalein as indicators.
The apparatus used were optical rotation analyser, conical flasks, 10mL and 50mL pipettes, burette, electronic weigh balance and beakers.
2.2. Methods:
a) Specific optical rotation: 21ÌŠ to 27ÌŠ
1.25g N-acetylcysteine powder was weighed and allowed dissolve in a mixture of 1ml of 10g/L solution of disodium edentate, 7.5ml of 1M sodium hydroxide and sufficient amount of mixed phosphate buffer pH 7.0 to 25ml total volume. Optical rotations of the freshly prepared solution and the old solutions of N-acetylcysteine provided were measured and recorded.
b) ASSAY: 98.0%-101.0% C5H9NO3S (as dried material)
0.14g N-acetylcysteine powder was weighed by difference and poured into a conical flask. 60 ml of water and 10ml dilute hydrochloride acid were measured and added into the conical flask. The conical flask was shaking to ensure the N-acetylcysteine powder was fully dissolved. The solution was left to cool. Another 10ml of potassium iodide solution was added into the cooled solution in the conical flask. The solution was then titrated with 0.05M iodine by using starch as indicator. Second titration was carried out to ensure accurate and precise result.
c) Assay by titration with 0.1M sodium hydroxide
0.3g N-acetylcysteine powder was weighed by difference and poured into a clean conical flask. Approximately 50 ml of distilled water was measured and added into the conical flask. The conical flask was shaking to ensure the N-acetylcysteine powder was fully dissolved. The solution was titrated with 0.1M sodium hydroxide using phenol red as indicator. Second titration was carried out to ensure accurate and precise result.
0.3g N-acetylcysteine powder was weighed by difference and poured into a clean conical flask. Approximately 50 ml of distilled water was measured and added into the conical flask. The conical flask was shaking to ensure the N-acetylcysteine powder was fully dissolved. The solution was titrated with 0.1M sodium hydroxide using phenolphthalein as indicator. Second titration was carried out to ensure accurate and precise result.
d) Zinc: Not more than 10ppm Zinc
1.00g of N-acetylcysteine powder was weighed and dissolved in 0.001M hydrochloric acid. The solution was diluted to 50ml with 0.001M hydrochloric acid and solution 1 was obtained.
Three solutions were prepared for analysis. The first solution consists of 10ml solution 1 diluted to 20ml with 0.001M hydrochloric acid, second solution consists of 10ml solution 1 and 1ml of 5ppm zinc standard diluted to 20ml with 0.001M hydrochloric acid and the third solution consists of 10ml solution 1 and 2ml of 5ppm zinc standard diluted to 20ml with 0.001M hydrochloric acid.
The absorbance of each solution was measured at 213.8nm using an atomic absorption spectrophotometer. The absorbance for each solution was tabulated. The zinc content in each sample was calculated using the method of standard addition.
e) Loss on drying: Not more than 1.0%w/w
A sample of N-acetylcysteine was dried at 70ÌŠ C in vacuo for 3 hours and the data was recorded and the percentage loss on drying of this sample was calculated.
f) Related substances
The chromatograms obtained from the HPLC analysis of both fresh solution and old solution of N-acetylcysteine was examined.
3. Results: a) Specific optical rotation:
Mass of weighing boat(g)
26.6089
Mass of weighing boat sample (g)
27.8609
Mass of weighing boat residue (g)
26.6079
Mass of sample transferred (g)
1.253
Table 1: The mass of N-acetylcysteine used to make a solution for measurement of specific optical rotation.
Calculations: According to British Pharmacopoeia (BP 1999; page 40-41), it states that the specific optical rotation is  21.0 to  27.0. To obtain the angle of rotation, the equation below is used,
Where, [α] = specific optical rotation
α = observed angle of rotation
C = concentration of active substance in g/100mL of the solution
l = length of column in 2dcms
For freshly prepared solution: Angle obtained (α): 2.45⁰
Concentration of N-acetylcysteine (c): 5.012 %w/v
Path length = 2 dm
Specific optical rotation:
= 100 x 2.45⁰
2 x 5.012g/ml
= 24.5⁰ For old solution: Angle obtained (α): -3.29⁰
Concentration of N-acetylcysteine (c): 5.012 %w/v
Path length = 2 dm
Specific optical rotation:
= 100 x 3.29⁰
2 x 5.012g/ml
= -32.9⁰ b) ASSAY: 98.0%-101.0% C5H9NO3S (as dried material)
Sample 1
Sample 2
Mass of boat sample (g)
3.8797
3.8777
Mass of boat residue (g)
3.7393
3.7398
Mass of Acetylcysteine transferred (g)
0.1404
0.1379
Table 2: The mass of N-acetylcysteine powder in sample 1 and sample 2 for titrations with iodine.
First reading Second reading Initial volume (mL)
17.40
26.70
Final volume (mL)
26.40
35.50
Volume of 0.05M iodine used (mL)
9.00
8.80
Table 3: The volume of iodine used for both titration using sample 1 and sample 2 of N-acetylcysteine solution and starch as indicator.
Calculations: Actual concentration of iodine used: 0.0476M
Molecular weight of N-acetylcysteine (C5H9NO3S): 163.2
The balanced equation for the reaction between N-acetylcysteine and iodine:
2 C5H9NO3S I2 à C5H8NO3SSC5H8NO3 2HI 2KI à I2 2K According to British Pharmacopoeia, 1mL of 0.05M iodine is equivalent to 16.32mg of C5H9NO3S. This means, 2 mole of C5H9NO3S equal to one mole of iodine.
Therefore when 1mL of 0.05M iodine = 16.32mg of C5H9NO3S,
1mL of 0.0476M iodine = 0.0476M x 16.32mg/ 0.05M
= 15.54mg of C5H9NO3S First titration: 1mL of 0.0476M iodine = 15.54mg of C5H9NO3S
So, 9.00mL of 0.0476M iodine = 9.00mL x 15.54mg/ 1mL
= 139.86mg
= 0.13986g of C5H9NO3S Second titration: 1mL of 0.0476M iodine = 15.54mg of C5H9NO3S
So, 8.80mL of 0.0476M iodine = 8.80mL x 15.54mg/ 1mL
= 135.52mg
= 0.13552g of C5H9NO3S Calculation of Percentage of Purity: Sample 1 of N-acetylcysteine Sample 2 of N-acetylcysteine Mass transferred
Actual mass calculated
Mass transferred
Actual mass calculated
0.1404
0.1399
0.1379
0.1355
According to British Pharmacopoeia (BP), the percentage of purity should be within 98.0 – 101.0% of dried substance.
Equation of the Percentage of Purity: Sample 1: Sample 2: c) Assay by titration with 0.1M of sodium hydroxide i) Titration by using phenol red indicator
Sample 1 Sample 2 Mass of boat sample (g)
3.8916
3.9199
Mass of boat residue (g)
3.5913
3.6198
Mass of N-acetylcysteine transferred (g)
0.3003
0.3001
Table 4: The mass of N-acetylcysteine powder in sample 1 and sample 2 for titrations with 0.1M of sodium hydroxide.
First reading Second reading Initial volume (mL)
1.00
1.00
Final volume (mL)
18.15
18.10
Volume of 0.05M iodine used (mL)
17.15
17.10
Table 5: The volume of 0.1M sodium hydroxide used for both titration using sample 1 and sample 2 of N-acetylcysteine solution and phenol red as indicator.
Calculations: Actual concentration of sodium hydroxide (NaOH) used: 0.1062M
Molecular weight of N-acetylcysteine (C5H9NO3S): 163.2
The balanced equation for the reaction between N-acetylcysteine and sodium hydroxide (NaOH):
C5H9NO3S NaOH à C5H8NO3SNa H2O From the equation, one mole of N-acetylcysteine reacts with one mole of NaOH. So the reaction is a 1:1 ratio. To find out the number of mole of NaOH, the equation below is used:
First titration: Moles of NaOH = (0.1062M x 17.15mL)/1000
= 1.821 x10-3 moles
As the reaction is 1:1 ratio so the number of moles of N-acetylcysteine is equal to the number of moles of NaOH used which is 1.821 x10-3 mole.
Mass of N-acetylcysteine = 1.821 x10-3 moles x 163.2
= 0.2972g Second titration: Moles of NaOH = (0.1062M x 17.10mL)/1000
= 1.816 x10-3 moles
As the reaction is 1:1 ratio so the number of moles of N-acetylcysteine is equal to the number of moles of NaOH used which is 1.821 x10-3 mole.
Mass of Acetylcysteine = 1.816 x10-3 mole x 163.2
= 0.2964g Calculation of Percentage of Purity: Sample 1 of N-acetylcysteine Sample 2 of N-acetylcysteine Mass transferred
Actual mass calculated
Mass transferred
Actual mass calculated
0.3003
0.2972
0.3001
0.2964
According to British Pharmacopoeia (BP), the percentage of purity should be within 98.0 – 101.0% of dried substance.
Equation of the Percentage of Purity:
Sample 1: Sample 2: ii) Titration by using Phenolphthalein as the indicator
Sample 1 Sample 2 Mass of boat sample (g)
3.8916
3.9195
Mass of boat residue (g)
3.5915
3.6195
Mass of N-acetylcysteine transferred (g)
0.3001
0.3000
Table 6: The mass of N-acetylcysteine powder in sample 1 and sample 2 for titrations with 0.1M of sodium hydroxide.
First reading Second reading Initial volume (mL)
18.20
17.10
Final volume (mL)
36.80
36.95
Volume of 0.05M iodine used (mL)
18.60
19.85
Table 7: The volume of 0.1M sodium hydroxide used for both titration using sample 1 and sample 2 of N-acetylcysteine solution and phenolphthalein as indicator.
Calculations: Actual concentration of sodium hydroxide (NaOH) used: 0.1062M
Molecular weight of N-acetylcysteine (C5H9NO3S): 163.2
The balanced equation for the reaction between N-acetylcysteine and sodium hydroxide (NaOH):
C5H9NO3S NaOH à C5H8NO3SNa H2O From the equation, one mole of a N-acetylcysteine reacts with one mole of NaOH. So the reaction is a 1:1 ratio. To find out the number of mole of NaOH, the equation below is used:
First titration: Moles of NaOH = (0.1062M x 18.60mL)/1000
= 1.975 x10-3 mole
As the reaction is 1:1 ratio so the number of moles of N-acetylcysteine is equal to the number of moles of NaOH used which is 1.821 x10-3 mole.
Mass of N-acetylcysteine = 1.975 x10-3 mole x 163.2
= 0.3224g Second titration: Moles of NaOH = (0.1062M x 19.85mL)/1000
= 2.108 x10-3 mole
As the reaction is 1:1 ratio so the number of moles of N-acetylcysteine is equal to the number of moles of NaOH used which is 1.821 x10-3 mole.
Mass of N-acetylcysteine = 1.816 x10-3 mole x 163.2
= 0.3440g Calculation of Percentage of Purity: Sample 1 of N-acetylcysteine Sample 2 of N-acetylcysteine Mass transferred
Actual mass calculated
Mass transferred
Actual mass calculated
0.3001
0.3224
0.3000
0.3440
Calculation of Percentage of Purity: According to British Pharmacopoeia (BP), the percentage of purity should be within 98.0 – 101.0% of dried substance.
Equation of the Percentage of Purity:
Sample 1: Sample 2: d) Zinc: Not more than 10ppm Zinc (Zn): To determine the concentration of Zinc metal present in a standardised sample, atomic absorption spectrophotometer was applied. This was done so as to comply with the British Pharmacopoeia (BP) standards, where the detected concentration of Zinc should not be more than 10ppm.
Mass of Acetylcysteine sample used: 1.00g This sample was diluted accordingly and then analysed or measured by an atomic absorption spectrophotometer at a set wavelength of 213.8nm. According to the laboratory transcript, the absorbances were given, so the calculation was carried out to determine the concentrations for each solution.
Solution Concentration (mg/L) Absorbance (at 213.8nm) (a) 0.00
0.056
(b) 0.25
0.115
(c) 0.50
0.173
Table 8: The absorbance of solution a, b and c using atomic absorbance spectrophotometer.
From the table 8 above, a standard additions calibration graph of concentration of zinc in mg/L against absorbance at 213.8nm is plotted. A rather small absorbance indicates that there is a trace or small amount of Zinc (Zn) present in Solution A, which practically contained only the N-acetylcysteine sample. Hence, we can plot a line of best fit and extrapolate to find the concentration of Zn present within our sample. Note that the amount of Zn present is proportional to the absorbance detected at 213.8nm wavelength.
Graph 1: The graph of absorbance against concentration of Zinc.
Extrapolated value= -0.24 Solution A = 0.24ppm Solution 1 = 0.24 Ã- 2 = 0.48 ppm
Solution 1 0.48g in 100 000 mL = 2.4 Ã- 10-4g in 50 mL
If 1g of N-acetylcysteine contains 2.4 Ã- 10-4g of zinc ions, 104g of acetylcysteine will contain 2.4g of zinc ions.
So concentration of zinc ions in N-acetylcysteine = 2.4ppm
Using the calibration graph, we obtained an equation for the line of best fit as shown below:
Using the line of best fit we can calculate the concentration of Zinc (Zn) present within Solution 1. This is determined by the difference between the origin (x = 0) and where the line of best fit intercepts the x-axis. To be more accurate, the equation of the line of best fit can be used by assuming the absorbance of N-acetylcysteine at 213.8nm (y-axis) is 0 (y = 0). We can then calculate and find the exact concentration of Zn added (x-axis in mg/L) which gives an absorbance reading of 0.0562 at the wavelength of 213.8 nm. This calculation is shown below where absorbance y = 0.
Concentration of Zinc in solution (a) where no Zinc is added:-
(Concentration comes in positive value)
Therefore, the diluted Solution 1 contains an exact concentration of 0.2402mgL-1 or 0.2402ppm. We can now use this concentration and work backwards from the dilution to obtain the mass of Zn within the 20mL Solution 1, as shown in the calculation below,
Mass of Zinc in Solution 1:-
From the mass of Zinc present in Solution 1 as calculated, we can say that this equals to the 10mL of N-acetylcysteine sample in Solution (a). This is because Solution 1 was diluted to 20mL using 0.001M hydrochloric acid and contained no other sources of Zinc. Hence, 4.8034μg of Zinc in 20mL of Solution 1 is equal to 4.8034μg of Zinc in 10mL of Solution (a). Now using this mass of 4.8034μg in 10mL of Solution (a) we can find out the total mass of Zinc within 50mL. However, the total mass of Zinc within 50mL of Solution (a) is equivalent to 1.00g of N-acetylcysteine sample which is the original sample mix. Using these data, the mass of Zinc can be calculated as shown in the calculation below,
Mass of Zinc in 1.00g of N-acetylcysteine: – Hence, 2.4017μgmL-1 of Zinc is present in 1.00g. We can now calculate an exact concentration of Zinc in parts per million (ppm) as shown in the calculation below,
Concentration of Zinc within sample in ppm:-
e) Loss on drying: Not more than 1.0% w/w:- Initial mass of N-acetylcysteine sample (g)
1.0965
Mass after drying under specified conditions (g)
1.0893
f) Related substances 1) Acetylcysteine: fresh sample 8.57mg/mL
From British Pharmacopoeia, the retention time for the N-acetylcysteine substances as below.
Substance Retention time (min) L- cystine
About 2.2
L- cysteine
About 2.4
2-methyl-2 thiazoline-4 carboxylic acid
About 3.3
N,N’-diacetyl-L- cystine
About 12
N,N’-diacetyl-L- cysteine
About 14
acetylcysteine
About 6.4
1) Acetylcysteine: fresh sample 8.57mg/mL
Substance Retention time (min) Peak retention time obtained Concentration L- cystine
About 2.2
1.93
0.5948
L- cysteine
About 2.4
– – 2-methyl-2 thiazoline-4 carboxylic acid
About 3.3
3.25
0.0794
N,N’-diacetyl-L- cystine
About 12
– – N,N’-diacetyl-L- cysteine
About 14
13.623
0.3944
Acetylcysteine
About 6.4
6.972
94.7507
Calculation of impurities:
Peak area/ Total area x 100 Substance Area Concentration Impurity L- cystine
238606
0.5948
0.5948
L- cysteine
– – – 2-methyl-2 thiazoline-4 carboxylic acid
31861
0.0794
0.0794
N,N’-diacetyl-L- cystine
– – – N,N’-diacetyl-L- cysteine
158211
0.3944
0.3944
Acetylcysteine
38007440
94.7507
94.7507
Total area= 40113072 2) Acetylcysteine: old sample 2.5mg/mL
Substance Retention time (min) Peak retention time obtained Concentration L- cystine
About 2.2
2.11
0.7214
L- cysteine
About 2.4
– – 2-methyl-2 thiazoline-4 carboxylic acid
About 3.3
3.256
0.8946
N,N’-diacetyl-L- cystine
About 12
– – N,N’-diacetyl-L- cysteine
About 14
13.415
15.3284
Acetylcysteine
About 6.4
6.34
33.7241
Calculation of impurities:
Peak area/ Total area x 100 Substance Area Concentration Impurity L- cystine
62935
0.7214
0.7214
L- cysteine
– – – 2-methyl-2 thiazoline-4 carboxylic acid
78046
0.8946
0.8946
N,N’-diacetyl-L- cystine
– – – N,N’-diacetyl-L- cysteine
1337263
15.3284
15.3284
Acetylcysteine
2942118
33.7241
33.7241
Total area= 8724087 3) Cysteine/ cystine: 0.5mg/mL
Substance Retention time (min) Peak retention time obtained Concentration L- cystine
About 2.2
2.018
5.2956
L- cysteine
About 2.4
2.323; 2.65
2.3189; 2.384
2-methyl-2 thiazoline-4 carboxylic acid
About 3.3
3.008; 3.207
24.9029; 65.0987
N,N’-diacetyl-L- cystine
About 12
– – N,N’-diacetyl-L- cysteine
About 14
– – Acetylcysteine
About 6.4
– – Calculation of impurities:
Peak area/ Total area x 100 Substance Area Concentration Impurity L- cystine
87001
5.2956
5.2956
L- cysteine
38097; 39167
2.3189; 2.384
2.3189; 2.384
2-methyl-2 thiazoline-4 carboxylic acid
409128; 1069503
24.9029; 65.0987
24.9029; 65.0987
N,N’-diacetyl-L- cystine
– – – N,N’-diacetyl-L- cysteine
– – – Acetylcysteine
– – – Total area= 1642895 4. Discussion: a) Specific optical rotation:
The specific rotation of a chemical compound [α] is defined as the observed angle of optical rotation α in stereochemistry, when plane-polarized light is passed through a sample with a path length of 1 decimetre (dm) and a sample concentration of 1 gram (g) per 1 millilitre (mL). The specific rotation of a pure material is an intrinsic property of that material at a given wavelength and temperature. The reading should be accompanied by the temperature at which the measurement was performed and the solvent in which the material was dissolved, and this often assumed to be room temperature. The exact unit for specific rotation values is deg dm−1cm3 g−1 or can use degrees (̊). Levorotatory rotation (l) means a negative reading obtained and the rotation being to be left. While dextrorotatory rotation (d) means a positive reading and the rotation is being to be right. The specific optical rotation for the freshly prepared solution of N-acetylcysteine is 24.5⁰ which it is dextrorotatory rotation and the old solution of N-acetylcysteine is -32.9⁰ which means levorotatory rotation.
Measurement of optical rotation is a way to assess optical purity of a sample containing a mixture of enantiomers. An enantiomer is one of two stereoisomers that are mirror images of each other that are “non-superposable” or not identical much as one’s left and right hands are “the same” but opposite. The specific optical rotation of N-acetylcysteine solution is within the range 21ÌŠ to approximately 27ÌŠ. The freshly prepared of N-acetylcysteine solution is found to be in the range however the old N-acetylcysteine solution is not in the range. This reveals stability alteration occurred in the old N-acetylcysteine solution. The impurities have found in the old N-acetylcysteine solution because the presence of small amount of impurities can affect the rotation of the sample.
The actual optical rotation value for freshly prepared N-acetylcysteine solution is measured by single polarimeter because if the sample is very concentrated or it has very large specific rotation or the sample larger than 180°, single polarimeter cannot be used. The variation of specific rotation with wavelength is the basis of optical rotary dispersion (ORD) which used to elucidate the absolute configuration of certain samples. High performance liquid chromatography (HPLC) is used to determined the enantiomeric ratio with a chiral column because the aggregation in the N-acetylcysteine solution cause optical rotation of a sample maybe not linear dependent due to enantiomeric excess.
b) ASSAY: 98.0%-101.0% C5H9NO3S (as dried material)
From the result obtained above, the mass obtained from the titration of N-acetylcysteine solution with iodine with starch as indicator for first titration is 0.13986g and second titration is 0.13552g. The percentage of purity obtained from the experiment for first sample is 99.64%. The percentage of purity from second sample is 98.26%. According to British Pharmacopoeia (BP), the percentage of should be within 98.0 – 101.0% of dried substance. The percentage of purity for both samples is within the range stated in the BP. BP prefer the iodine titration to a titration using sodium hydroxide because iodine is a very useful oxidising titrant which react with reducing agent ,N-acetylcysteine solution using starch as indicator. Iodine forms an intensely dark blue complex with starch. Starch is an oxidation – reduction indicator that shows a reversible colour change between the oxidised and reduced forms. It is not affected by the presence of iodide (I-). Both starch and iodide must be present for the starch to change colour during the titration. Iodine is consumed by thiosulfate in the titration step. The amount of thiosulfate used is proportional to the amount of iodine liberated from the salt. Sodium hydroxide is a strong base. It is more useful in acid- base titration using weak acid or base indicator.
c) Assay by titration with 0.1M of sodium hydroxide
From the result obtained in this experiment, the mass obtained from the titration of N-acetylcysteine solution with0.1M sodium hydroxide with phenol red as indicator for first titration is 0.2972g and second titration is 0.2964g. The percentage of purity obtained from the experiment for first sample is 98.97%. The percentage of purity from second sample is 98.77%. According to British Pharmacopoeia (BP), the percentage of should be within 98.0 – 101.0% of dried substance. The percentage of purity for both samples is within the range stated in the BP.
The mass obtained from the titration of N-acetylcysteine solution with 0.1M sodium hydroxide with phenolphthalein as indicator for first titration is 0.3224g and second titration is 0.3440g. The percentage of purity obtained from the experiment for first sample is 107.43%. The percentage of purity from second sample is 114.67%. According to British Pharmacopoeia (BP), the percentage of should be within 98.0 – 101.0% of dried substance. The percentage of purity for both samples is out of the range stated in the BP.
Phenol red and phenolphthalein are acid-base indicators. The un-dissociated form of the indicator is a different colour than the iogenic form of the indicator. An Indicator does not change colour from pure acid to pure alkaline at specific hydrogen ion concentration, but rather, colour change occurs over a range of hydrogen ion concentrations. This range is termed the colour change interval. It is expressed as a pH range. The pH range for phenol red is 6.8- 8.4 and phenolphthalein is 8.0- 10.0. The selection of indicator will depend on the actual expected pH at the equivalence point which selects an indicator with a pKa right in the middle of the pH change at the equivalence point. N-acetylcysteine solution has pKa 4.0 and 9.5, and a weak acid indicator has to be used to determine the end point of the titration. Phenol red produce a good result compared to the phenolphthalein as indicator when titrate N-acetylcysteine solution with 0.1M sodium hydroxide.
d) Zinc: Not more than 10ppm Zinc (Zn):
By performing the atomic absorbance technique, we have determined that the N-acetylcysteine sample contained a Zinc concentration of 2.4017ppm. This sample complied with the requirement from the British Pharmacopoeia (BP) monograph standards by not having a Zinc concentration of greater than 10ppm.
Atomic absorbance technique can only detect specifically one heavy metal at a time. So, it is very time consuming to detect a wide spectrum of heavy metal impurities within our sample. Plus, the N-acetylcysteine monograph only indicates the need to monitor the level of Zinc present within the sample by atomic absorbance spectrometry. Therefore, to detect other heavy metals we would prefer to use the more generic “Limit Test C for Heavy Metals” as specified in the British Pharmacopoeia (2008), Volume IV, and Appendix VII.
e) Loss on drying: Not more than 1.0% w/w:-
According to British Pharmacopoeia (BP), it states that there should be no more than 1.0% in mass. This sample is complied with the BP monograph standards with a loss of only 0.66% in mass.
f) Related substances:-
HPLC is used in pharmaceutical analysis to quantitative determinations of drugs in formulations. These analyses do not require long time to optimising mobile phase and selecting columns and detectors. Some formulations contain more than one active ingredient and may present more of an analytical challenge since the different ingredients may have quite different chemical properties and elute at very different times from HPLC column.
5. Conclusions: Quality control is an essential operation of the pharmaceutical industry. Drugs must be marketed as safe and therapeutically active formulations whose performance is consistent and predictable. A bundle of sophisticated analytical methods are being developed for the drugs evaluation in pharmaceutical industry. Requirements governing the quality control of pharmaceuticals in accordance with the British Pharmacopoeia (BP) or European Pharmacopoeia.
Titration is a procedure used in chemistry in order to determine the molarity of an acid or a base. A chemical reaction is set up between a known volume of

Mosquito: Diseases and Control

Mosquitoes: The Diseases They Carry and Methods of Controlling the Populations
People who live in Alaska are definitely aware of the tiny insect known as the Mosquito. Most people do not realize the deadly diseases that they may carry and the possible effects that commonly used repellants may have. There are three main diseases carried and transmitted by mosquitoes, they are: West Nile, Malaria, and Dengue. Although these diseases are more prevalent in tropical areas, there is still a high risk for the citizens of Alaska of contracting one of these deadly diseases.
Many people drench themselves in repellants, many containing N-diethyl-meta-toluamide (DEET), but are there alternatives? There are as many as 230 products containing the chemical DEET known to the EPA, but there are many alternatives to using DEET, such as citronella and essential oils (Hayhurst). DEET has been approved by the EPA for years to help deter mosquitoes from biting.
One of the most widely used ways in which modern society tried to control mosquitoes was by spraying dichlorodiphenyltrichloroethane (DDT) over the Island of Sardinia, and island off the coast of Italy. Malaria had been present, but not prevalent until World War II malaria raged to the status of a full on epidemic. The Italian government and a private foundation enlisted the help of 25,000 people working in the field, 5 air craft, two helicopters, countless automobiles, and many field offices. The mosquito that was the subject of the extermination was the Anopheles labranchiae, the known carrier of malaria on the island. This species of mosquito has a soft body, brow coloring, and four dark marks on each wing. Not only did the workers attack the breeding locations of the mosquitoes, but they also sprayed homes, rivers, ponds, and fields with the DDT. In the extermination effort the workers used around 256 tons, 260,000 kilograms, of DDT. The effort was only partially successful. The number of reported malaria cases dropped to just 4 reported cases four years after the dusting, but when scouts went out to search for the Anopheles labrachiae they found that both adults and the larvae in the brackish streams and swamps. In the minds of the Italian government this was a failure (Andrew Spielman Sc.D 148-49).
Although the mosquito extermination was seen as a failure, the initial consensus in Greece, where 16% of children tested positive for malaria parasites, was that the use of DDT was a success. There were very few accidental deaths of other insects. Around 1942 over 50 percent of the population of Greece had been infected with malaria. In 1947 the government set out to eradicate the local carrier of malaria, Anopheles sacharovi. The citizens of Greece welcomed the workers who dusted the country as a “liberating army” (Andrew Spielman Sc.D 149)
There were also positive effects on crops. Olive farmers were fortunate to get their olive trees dusted, which killed off the caterpillars that in previous years had destroyed the crops. They were able to have a much larger harvest. Many towns experienced a reduction in all pests, including cockroaches, lice, and fleas, along with the mosquitoes. Soon after the dusting began malaria was gone from the islands. The citizens couldn’t be happier, until something unexpected happened (Andrew Spielman Sc.D 149).
The scientists were having lunch out in the country, and began to notice the flies returning. They were not overly concerned until they saw the dreaded Anopheles sacharovi flying around them. They scientists could not understand how the mosquitoes were surviving in a place that had been dusted with DDT. It was soon realized that the deadly malaria carrying Anopheles sacharovi had adapted and become DDT resistant. After this discovery scientists discovered how to use the pesticide to upset the cycle of malaria infections (Andrew Spielman Sc.D 149-50).
Although DDT was widely used all across the world, a successful mosquito eradication campaign was started in 1900 in New Jersey. Before the start of this rigorous campaign certain low lying areas of large metropolitan areas were uninhabitable because of the high populations of mosquitoes. A scientist by the name of John B. Smith began the campaign and only had rudimentary knowledge of the mosquito behaviors and species in the state. The first state was to identify the dominant species transmitting the malaria. He then identified the most common breeding areas of the mosquitoes of the area, the Ochlerotatus sollicitans and the Anopheles quardrimaculatus. This kind of mosquito particularly liked to breed in brackish water and swamps. Smith termed this effort “mosquito control” instead of extermination. At first this idea was completely rejected until the results of this revolutionary idea started to appear. Smith sent his crews all over the state to dig drainage ditches that would attract the mosquitoes for breeding. After the mosquitoes had laid their eggs in the ditches, the workers went back and filled them with oil. This caused the population of malaria carrying mosquitoes to drop dramatically in the areas where this technique was utilized. This had a positive secondary effect on the economy of the larger cities such as Newark and Elizabeth. There was a housing boom in the formerly unlivable areas and a population growth. In addition to these effects, the cases of malaria were diminished to only a few. These original ditches are still in use today across the states of New Jersey and New York (Andrew Spielman Sc.D).
Malaria is one of the most widespread diseases transmitted by mosquitoes carrying the parasite. There are as many as 50 types of malaria carrying Anopheles mosquitoes around the world (Major mosquito-borne diseases). The Anopheles mosquito tends to bite at night, why every person needs to sleep under a mosquito net in areas ravaged with malaria (Brody). The parasite that causes malaria is the Plasmodium. There are four kinds of Plasmodium that affect humans. They are: Plasmodium falciparum, Plasmodium vivax, Plasmodium malariae, Plasmodium ovale. The most common are Plasmodium falciparum and Plasmodium vivax. One of these happens to be the most dangerous, Plasmodium falciparum (WHO). Even though malaria is a parasitic disease, it is 100 percent preventable and also can be cured with the proper medication. The first symptoms of malaria tend to begin about ten to fifteen days. After the ten to fifteen days the first symptoms tend to be a fever, headache, chills, and vomiting (WHO). Travelers who do not have immunity and pregnant women, even those who have partial immunity, are at the highest risk for contracting malaria from an infected mosquito (WHO).
The most widely used medication to cure malaria is artemisinin-based combination therapies (ACTs). The best chance for curing a patient is early diagnosis and treatment with these medications. Not only is curing the already infected important, but disease prevention, especially in low income countries, is key. In the developing nations of malaria, the disease has a large impact on the economy and but a burden on the country as a whole. The one down side to these widely used drugs is that the Plasmodium parasites are quickly developing a resistance to them. To avoid the resistance people are now using ACTs as well as artemisinin monotherapy (WHO).
According to Jane Brody, in recent years there has been a large increase in the number of cases of dengue fever. This mosquito-borne disease is not directly transmitted from human to human, but is transmitted through mosquitoes. If a mosquito bites an infected human, and then bite a non-infected human, the disease will be spread. The main mosquito that transmits the dengue fever is the Aedes aegypti, which likes to bite during the day especially in the morning and late afternoon (Brody).
There are four kinds of the virus that cause dengue fever. They are a flavivirus and all vary slightly, but the four kinds are DEN-1, DEN-2, DEN-3, and DEN-4. Once a human being is infected with one of the four kinds of dengue fever, they have a life time of immunity to that particular type, but are still susceptible to a secondary infection from any of the other 3 types. Research shows that it is most likely the second infection, instead of the third or fourth, that can lead to dengue hemorrhagic fever, which is much more deadly. When this happens a person’s capillaries begin to leak fluid. The person does not die from dengue hemorrhagic fever, but rather dengue shock syndrome due to extreme blood loss (Brody).
According to the author of an article in Natural History Magazine, dengue fever may be deadly; the mortality rates are not high. The virus can only live for a short time in a human host and only has an incubation period of between four and seven days. The kinds of mosquitoes that are carriers of the virus are Aedes aegypti, Aedes polynesiensis, and Aedes albopictus. As the Aedes albopictus begins to spread into the western hemisphere, there is a greater risk for people in the United States of contracting this virus. After a person has been infected with a form of dengue they have some immunity against yellow fever and vice versa (Major mosquito-borne diseases).
The West Nile virus was first seen in Uganda around the West Nile region, hence the name, in the mid 1900s. Although this disease has been recognized for over 70 years, the first cases appeared in the United States in 1999. Once the disease hit America, the virus spread at an alarming rate across the country and is now reported in almost every state. Even though the virus is wide spread, it is rare to contract this disease. If it is contracted, the symptoms are usually not severe and tend to manifest like a mild case of the flu. The virus become deadly when a person is elderly or has a compromised immune system. If a person with such a condition becomes infected with the virus West Nile becomes deadly because the risk of encephalitis, also known as swelling of the brain, occurring goes up (Tufts University). Certain birds in the United States are the main carriers of the West Nile virus. Those birds are crows and jays. The mosquitoes pick up the virus when they bite an infected bird and the virus then goes to the insects’ salivary glands. Once an infected mosquito bites a human, the virus incubates for between two and fourteen days. There are other ways, although extremely uncommon, that West Nile can be transmitted. They are: organ transplant, blood transfusion, mother to unborn child, breast-feeding, and laboratory acquisition (Mayo Clinic Staff).
The mosquito is a vector of many different diseases, the most common being malaria, dengue fever, and West Nile virus. Many people over the years have tried to eradicate the tiny insect in an effort to prevent disease. Today a solution is needed for the growing mosquito problem across the globe that has not only killed millions in Africa, but is beginning to claim lives in the Northern Hemisphere, including lives in the United States. If steps are not taken to address this problem, tens of millions of people will fall victim to the diseases carried by this tiny insect benign in appearance. The mosquito may seem nonthreatening, and the bite an annoyance, but the itchy welt may spell out disaster for humans in every country of the world.

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