N Acetylcysteine Quality Control

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: +21ÃÅ'Ã…   to +27ÃÅ'Ã…   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 70ÃÅ'Ã…   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, [ÃŽÂ ±] = specific optical rotation ÃŽÂ ± = 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 (ÃŽÂ ±): 2.45à ¢Ã‚ Ã‚ ° Concentration of N-acetylcysteine (c): 5.012 %w/v Path length = 2 dm Specific optical rotation: = 100 x 2.45à ¢Ã‚ Ã‚ ° 2 x 5.012g/ml = +24.5à ¢Ã‚ Ã‚ ° For old solution: Angle obtained (ÃŽÂ ±): -3.29à ¢Ã‚ Ã‚ ° Concentration of N-acetylcysteine (c): 5.012 %w/v Path length = 2 dm Specific optical rotation: = 100 x 3.29à ¢Ã‚ Ã‚ ° 2 x 5.012g/ml = -32.9à ¢Ã‚ Ã‚ ° 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 ÃÆ'- 2 = 0.48 ppm Solution 1 0.48g in 100 000 mL = 2.4 ÃÆ'- 10-4g in 50 mL If 1g of N-acetylcysteine contains 2.4 ÃÆ'- 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, 4.8034ÃŽÂ ¼g of Zinc in 20mL of Solution 1 is equal to 4.8034ÃŽÂ ¼g of Zinc in 10mL of Solution (a). Now using this mass of 4.8034ÃŽÂ ¼g 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, 2.4017ÃŽÂ ¼gmL-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 [ÃŽÂ ±] is defined as the observed angle of optical rotation ÃŽÂ ± 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 dmà ¢Ã‹â€ Ã¢â‚¬â„¢1cm3 gà ¢Ã‹â€ Ã¢â‚¬â„¢1 or can use degrees (ÃÅ'Ã…  ). 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-a cetylcysteine is +24.5à ¢Ã‚ Ã‚ ° which it is dextrorotatory rotation and the old solution of N-acetylcysteine is -32.9à ¢Ã‚ Ã‚ ° 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 ones left and right hands are the same but opposite. The specific optical rotation of N-acetylcysteine solution is within the range +21ÃÅ'Ã…   to approximately +27ÃÅ'Ã…  . 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 prese nt 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

All Children Can Learn and Most at High Levels

One of the founding principles of the Kentucky Education Reform Act is the statement that â€Å"All children can learn and most at high levels. † With many states having a significant achievement gap between diverse students, it is becoming more important to hold high expectations for all students. I believe that all children can learn and most at high levels. But my point is that not all the children can learn at high levels in the same field. As we know the student is the subject of education. Education aims to develope students' learning potential. But children from different environments have differences in their physiology, intelligence, ability, aptitude, interest, personality traits and emotional development. Therefore some children may gain a great success in music while some others may in math. If we can educate them according to their personalities and individual needs, most children can learn at high levels. American educator John Dewey (John Dewey ,1859-1952) has pointed out that there are plasticity and dependency in the process of one’s growth. This means that the development of a child has unlimited possibilities. The ancient Chinese educator, the Confucius put forward the idea that â€Å"No Child Left Behind† and † Teach students in accordance with their aptitude. † This can be regarded as the practice of the concept that â€Å"every child can learn and most at high levels†. Therefore, whether ancient or modern, Western or Eastern, educators all hold the same concept. We want children to be able to learn and success, the key is the teacher. A professional, high-quality and enthusiastic teacher will be a good fortune to the children. This is why personal development is a necessity to teachers. During these years of teaching I met a lot of challenges to confirm the special needs of children and develope their learning confidence. I always try my best to help each child and encourage them. To teach a student well needs the effort of all parties including parents, teachers and communities. As a home class teacher, I combine all the parties well to improve students' learning capacities and help them to form clear awareness of themselves. If the children in my class can tap all of their potentials, that will be a great success to me as a teacher. Nowadays, the competition is very fierce. Teachers have the obligation to educate their students to be more competitive in certain area in the society. We don’t have the right to give up any of the children. Today, we have to give up the child. Tomorrow, the child may give up the society. Society will pay a higher price.

Changing a Five Day School Week to a Four Day School Week Essay

Changing a five day week to a five day week to a four day week (For schools) Why is our traditional five day week changing to a four day week? Any reason? A four day week would result in extra hours of work, interference with family schedules and much more. In any case what’s the problem with the five day school week? The customary five day school week should stay without any alterations. There are many reasons that support the understanding of having a five day school week instead of changing it into a four day school week. Firstly, people are already used to the five day week and might have to put some changes to their regular habits. Secondly, parents at work would have a very hard time to find a person to take care of their child (babysitter); this would be a big problem for families with no money. In the third reason I speak about the kids interest areas. It would be a loss of time of their practice of their extra-curricular activities that they really enjoy from their choice classes. There are many reasons that support the understanding of having a five day school week instead of changing it to a five day school week. People are already used to the five day school week since centuries and there have not been a lot of problems with the system, so why change it right now? The four day week would make a big difference (bad changes) in their sleeping and eating habits(Proved out by the Canadian center for occupational health). Parents at work would also have a hard time finding a babysitter. They would have a hard time leaving their children alone at home. This would be a big problem for children and families who are poor and cannot afford a person to take care of their children during work. Everyone knows that education for children has an impact on the future of this country. Our education/ learning system has been going on pretty good or let’s just say progressing every day and taking a brake would obviously low the percentage down of getting all these things we hope for. Lots of high schools, middle schools and elementary schools have game time/P.  E which makes children active at least for sixty min. a day. Less activity time can lead to unhealthy diseases such as obesity. Many activities such as orchestra, robotics and arts are chosen by the child with their own interest. If a parent cannot afford a class (outside school) it would be hard for them to enjoy the lost time of the choice class they chose. Now I would like to add on more to my first reason of having a five day week instead of changing it to a four day week. All of us have been using the ive day week for centuries then why change it now? The four day week might bring a sudden change in sleep habits which in turn may cause drowsiness, laziness and other factors during working hours. The four day week might also bring sudden changes in eating habits from more regular parties and unhealthy food.. When you have another weekend, many people oversleep. You might also develop certain health problems from oversleeping on an extra holiday such as diabetes, heart diseases, stress, anxiety, apnea and many more. Another day of a holiday means more partying, and mainly eating more unhealthy food. Problems that you might develop from eating unhealthy food are: Obesity, Diabetes, bulimia, binge eating and many more. There are people out there fighting for a four day week. Let see a few of the other side’s arguments. Some say that having a four day week might help save gas money for the district. However school buses are used on weekends as a public transportation even more which in turn might get the gas costs higher instead of saving a whole bunch of money. Parents also say that children would have extra free time if allowed an extra weekend. But guess what? 70% of all kids in America would prefer to have school instead of an extra weekend. School is a place where you could interact with old friends and make new friends! Fun activities compiled with learning. What would be a better option? In conclusion I would want the school board to consider the decision of having a five day school week because of multiple reasons I told during my essay. Such as people are already used to the five day school week, poor parents and normal parents might have a hard time at work worrying about their children at work and having a babysitter, less education for the future, less activity time, less extra-curricular time and having less face-to-face time with the teacher. Therefore as a call to action I would go to the school board/superintendent and reject all proposals of having a four day week because of these several reasons. I would also write a petition/proposal regarding to keep the 5 day school week the same. This petition would include other parents signatures who agree with me.

Hate Crimes on the Rise in USA - 780 Words

Hate Crimes in the United States In many cities throughout the United States, hate crimes are on the rise. A hate crime is a traditional offense like murder, arson, or vandalism with an added element of bias. For the purposes of collecting statistics, Congress has defined a hate crime as a criminal offense against a person or property motivated in whole or in part by an offenders bias against a race, religion, disability, ethnic origin or sexual orientation (FBI, 2012). Hate crimes have increased as the national conversation has grown less tolerant. Therefore, it should come as no surprise that hate crimes against Latinos, Muslims, and homosexuals have seemingly increased in recent years. However, whether hate crimes are actually on the rise is something that is debated; the upswing in reported hate crimes may be due to an actual increase in crime rates, but it could also be due to an increase in reporting. There is no single person that commits hate crimes; they can be committed by a person of any race, sexual orientation, or cultural background. However, there is a typical individual who commits a hate crime, and those individuals come from majority groups. However, Of the 6,934 identified hate crime offenders, the majority were white (4,317, or 62.3%); 1,286 (18.5%) were black, 61 (0.9%) were American Indian or Alaskan Native, 93 (1.3%) were Asian or Pacific Islander, 741 (10.7%) were of unknown race, and the remaining 436 (6.3%) were of other races or multipleShow MoreRelatedIslam And Muslim Will Be Used Interchangeably857 Words   |  4 Pagescorrelations between American anti-Muslim hate crimes and global terrorist attacks. The thought was that because so many places were being attacked, American people would be more scared of Muslim peoples and commit more hate crimes. 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