Oil Never Sleeps Essays - Petroleum, Surfboard,

Oil Never Sleeps Recently while reading Surfer Magazine I came across a fascinating article called "Oil Never Sleeps". At first I thought it would ge just another "Environmental Complaint" or whining session. Surfers are always concerned with the ocean and the safety of using it. I was surprised to see a new view or perspective being used. In the past, oil contaminations were always told of from an etic point of view towards the oil industry. In this artilce, the author connects with the surfers and the oil industry as being part of both of them (Emic). His discussion making this inclusion was very clever. The surfboards, wetsuits, wax, and accessories are primarily made from petroleum. The transportation to the beach even uses and supports this beast that's been destroying the ocean and earth. His examination of the data is fairly thorough. It reminded me of class discussions about cultures that exploit nature versus those who live in harmony with it. All of this time I have felt myself to be one of the more environmentally aware people. I ride bicycle and skateboard locally to keep from using a car. Now after reading about "petroleum surfboards", I realize that bicycles have a lot more oil in them than you might think. All of the safety gear is oil, the helmet, pads, shoes, lycra shorts, bottles, even the wristwatch. The same applies to skateboarding. At this point I look up and see thousands of gallons of oil in my house. I'm surrounded by it. My sofas, phones, t.v., vcrs, planters, catbox, computer system, picture frames, all of my product containers, security system, bags, tapes, cameras, even the pen I'm using. I wear it, put it in my mouth twice a day to clean my teeth, massage my head for vanity with it, cover my eyes with it, talk to it, carry it in my pockets, buy groceries with it, get cash with it, and walk with it on my feet. It makes me ill thinking that I pointed the finger outward to lay blame on "them" when Exxon Valdez spilled our lover into the ocean. The culture of the industrial world has revolved around oil. It fights and kills for it. It's worse than any drug addiction and more powerful than money (which was printed on 50% oil based paper). This illness is limited to those of us above the farming level. The mode of subsistence for the whole world is oil, with exception of the rapidly disappearing natural inhabitants (tribes, animals, etc..). The author didn't look this deeply into the subject, but it did probe me to look at the whole picture about oil. Nevertheless, his picture of us and oil is just as terrible. The ending didn't give many reasonable solutions, there can always be safer ships, but until this "culture of oil" develops higher understanding or moves on, we will all have to deal with spills, land contamination, and acid rain. If the earth is our mother, then oil is our lover.

John F. Kennedys Legacy in Education and the Space Race

John F. Kennedy's Legacy in Education and the Space Race While the last photographs of John F. Kennedy preserve him eternally in Americas collective memory  as 46 years old,  he would have been 100 years old on May 29, 2017. Education was one of the signature issues of President Kennedy, and there are a number of legislative efforts and messages to Congress that he initiated to improve education in several areas: graduation rates, science, and teacher training. On Raising High School Graduation Rates   In a  Special Message to the Congress on Education,  delivered  on  February 6, 1962, Kennedy laid out his argument that  education in this country is the right- the necessity- and the responsibility- of all.   In this message, he noted the high number of high school dropouts: Too many- an estimated one million a year- leave school before completing high school- the bare minimum for a fair start in modern-day life. Kennedy referenced the  high percentage of dropouts in 1960, two years earlier. A data study  prepared by the  Institute of Educational Studies (IES) at the  National Center for Educational Statistics, showed the high school dropout rate in 1960 was at a high 27.2%. In his message, Kennedy also spoke about the 40% of students at that time who had started but never completed their college education.   His message to Congress also laid out a plan for increasing the number of classrooms as well as increased training for teachers in their content areas.  Kennedys  message to promote education had a powerful effect. By 1967, four years after his assassination, the total number of high school dropouts was reduced by 10% to 17%. The dropout rate has been falling incrementally ever since. As of 2014, only 6.5% of students drop out of high school. This is an increase of 25% in graduation rates from when Kennedy first promoted this cause. On Teacher Training and Education In his Special Message to the Congress on Education (1962), Kennedy also outlined his plans to improve teacher training by collaborating with the  National Science Foundation and the Office of Education.   In this  message, he proposed a system where, Many elementary and secondary school teachers would profit from a full year of full-time study in their subject-matter fields, and he advocated that these opportunities be created. Initiatives like teacher training were part of Kennedys New Frontier  programs. Under the policies of the New Frontier, legislation was passed to expand scholarships and student loans with  increases in funds for libraries and school lunches. There were also funds directed to teach the deaf, children with disabilities, and children who were gifted. In addition, literacy training was authorized under Manpower Development and Training Act (1962) as well as an allocation of Presidental funds to stop dropouts and the  Vocational Education Act (1963). Kennedy saw education as critical to maintaining the economic  strength of the nation.  According to Ted Sorenson,  Kennedys speechwriter, no other domestic issue occupied Kennedy as much as education. Sorenson quotes Kennedy as saying: Our progress as a nation can be no swifter than our progress in education. The human mind is our fundamental resource. On Science  and Space Exploration The successful launch of  Sputnik 1,  the first artificial Earth satellite, by  the Soviet space program  on October 4, 1957, alarmed American scientists and politicians alike. President  Dwight Eisenhower appointed the first presidential science adviser, and a Science Advisory Committee asked part-time scientists to serve as advisers for their initial steps. On April 12, 1961, only four short months into Kennedys presidency, the Soviets had another stunning  success. Their Cosmonaut Yuri Gagarin completed a successful mission to and from space. Despite the fact that the United States space program was still in its infancy, Kennedy responded to the Soviets with his own challenge, known as the moon shot, in which Americans would be the first to land on the moon.   In a speech  on  May 25, 1961, before a joint session of Congress, Kennedy proposed  space exploration to put astronauts on the moon, as well as other projects including nuclear rockets and weather satellites. He was quoted as saying: But we do not intend to stay behind, and in this decade, we shall make up and move ahead. Again, at  Rice University on September 12, 1962, Kennedy  proclaimed that America would have a  goal to land a man on the moon and bring him back by the end of the decade, a goal that would be directed to educational institutions: The growth of our science and education will be enriched by new knowledge of our universe and environment, by new techniques of learning and mapping and observation, by new tools and computers for industry, medicine, the home as well as the school. As the American  space program known as Gemini was pulling ahead of the Soviets, Kennedy gave one of his last speeches on October 22, 1963,  before the National Academy of Sciences, which was celebrating its 100th anniversary. He expressed his overall support for the  space program and emphasized the overall importance of science to the country: â€Å" The question in all our minds today is how science can best continue its service to the Nation, to the people, to the world, in the years to come†¦Ã¢â‚¬  Six years later, on July 20, 1969,  Kennedys efforts came to fruition  when Apollo 11 commander Neil Armstrong took a giant step for mankind and stepped onto the Moons surface.

Mechanical cavopulmonary assist device cage for Fontan patients Research Paper

Mechanical cavopulmonary assist device cage for Fontan patients - Research Paper Example Smaller size of the filaments limits the structural support ability of the protective cage while large sizes of the filaments decreases the hydrodynamic properties of the design while increasing the pressure. The size of the filament thickness is however subject to change based on computational test results. The number of filaments is proposed to be five, not the same as the number of impeller blades, in order to shun resonance and vibration of the system. The protective cage offers protection to the vessel from the rotating components through its radial arrangements of the filaments. The elliptical design of the protective cage of filaments not only presents hydrodynamic characteristics but also provides space efficiency. The angle designs of the blades helps in space conservation given that a number of the blades can be fitted within the pump for maximum functionality. This helps in minimizing the size of the pump to ensure it properly fits within the blood vessel. The pump is characterised with diffuser blades, which are located on the protective filament cage. A shift in the flow directionality aids the diffuser blades to convert the rotational force produced by the impellor to potential energy. A motor-magnetic bearing suspension is used to induce the pump rotation. The proposed design will aim to achieve this through the levitation and rotation of the impellor within the protective filament cage (Throckmorton et al., 2010). The protective cage of filaments is designed with five elliptically shaped filaments. The proposal aims at modifying the design to serve both protective and design functions at the same time. The shape of the protective cage filaments serves significant role in stabilizing the impeller blades radially and axially in addition to acting as a barrier in the protection of the vessel from the rotating impeller blades. The unique elliptical design shape of the filaments plays a vital role in maximizing energy production from impeller while

Assignment Essay Example | Topics and Well Written Essays - 500 words - 80

Assignment - Essay Example The disease is also causes fever, and red skin-spots that later turn black, thus the name â€Å"Black Death†. The disease reached Europe through The Black Sea in October 1347 when 12 Genoese trade ships arrived at Messina’s Sicilian port. The Genoese ships’ passengers on board were already plague-infected. The strategic location of China as one of the world’s significant trading nations facilitated the spread of the Black Death into Europe and Western Asia. The Black Death rapidly spread in â€Å"Europe from Italy, France, Spain, Portugal, England, Germany, Scandinavia, Norway, Bergen, Iceland, to northwestern Russia.†3 The medieval society was tremendously influenced by the Black Death. To begin with, there was starvation in the villages because the laborers died. The men who were supposed to plough fields died. The lack of labor also affected the harvesting, and livestock farming. In the urban areas, the effects of the Black Death were directly proportional to the impacts in the rural areas. A number of people migrated from the urban areas to the rural areas because it was believed that the fleas causing the Black Death was common in the urban areas. The urban areas suffered lack of food because the primary suppliers of food, who were the surrounding villages, could not supply adequate food. The loss of labor through deaths led to the lords resorting to sheep farming, as opposed to earlier grain farming. There was also shortage of commodities like bread because of the decline in grain farming. The prices of food in the urban areas skyrocketed because of the inflation. The inflation resulted into workers demanding for better pay, leading to the 1381’s Peasants Revolt in Europe when the landlords were hesitant to heed to the peasants’ demands.4 There were huge disruptions in the medieval world because of the Black Death. The Black Death led to the establishment of Feudal law restricting the movement of peasants, unless authorized by

Paraphrase Essay Example | Topics and Well Written Essays - 500 words

Paraphrase - Essay Example One inclusive cycle of the waveform, or the time in which it takes to complete, is referred to as a period. Another component of a sinusoid is the amplitude, or the total quantity of pressure variation surrounding the mean of the wavelength. The final specification of a sinusoid is the part of the cycle where the wave progresses relative to a particular fixed point in time, referred to as the phase. Phase is only a crucial aspect to consider for the measurement of continuous sinusoids, because one is forced to reflect upon the relationship between two or more different waves, rather than just a single wave. However, because the vowel is considered to be a complex waveform, it can be evaluated by converting the complex waveforms into a series of sinusoids distinguished by specific frequencies, amplitudes and phases. In doing so, it is determined that a vowel has two difference frequencies, one high and one low. The sinusoids of low frequency lean towards a higher amplitude, while the sinusoids of high frequency are nearly equally balanced in amplitude from the mean. The combination of two sinusoids of two different frequencies results in a complex wave. This is accomplished by adding low and high frequencies, in which the frequency is maintained in the resulting wave. Also, a complex wave can be formed by adding two amplitudes at a suitable point in time. The perceived shape of the complex wave is reliant upon the relative frequency, amplitude and phase of each aspect of the sine wave. Vowel acoustics are examined by the relative results of the formants. According to Benade in the 1976 study, formants are â€Å"the peaks that are observed in the spectrum envelope†. This can be observed through dark bands which appear on a spectrogram, signifying acoustic resonances emitted from the vocal tract. The vocal tract operates as a resonant cavity and the placement of certain facial features, including the tongue, jaw and lips, results in different

What Are The Uses Of Phenoxybenzamine Hydrochloride Biology Essay

What Are The Uses Of Phenoxybenzamine Hydrochloride Biology Essay Phenoxybenzamine Hydrochloride (RS)-benzyl(2-chloroethyl)1-methyl-2-phenoxyethylamine hydrochloride is a alpha-adrenoceptor blocker that covalently binds and irreversibly inhibits the activity of alpha-1 alpha -2 adrenoceptors.3,4 Phenoxybenzamine Hydrochloride is mainly used to treat episodes of high blood pressure and sweating related to phaeochromocytoma. Phaeochromocytoma is a rare catecholamine-secreting tumour of the adrenal medulla. Patients with phaeochromocytoma are usually hypertensive and suffer headache, palpitations, and excessive sweating.3 However it is rarely prescribed due to it unfavourable side effects. One of the side effects of Phenoxybenzamine is that block the ejaculation. Also some studies are under investigation to use Phenoxybenzamine as male contraceptive pills.11 , HCl Fig. 01 Molecular structure of (RS)-N-benzyl-N-(2-chloroethyl)-1- phenoxy-propan-2-amine Phenoxybenzamine hydrochloride is white, odourless, crystalline powder that is sparingly soluble in water; soluble in ethanol, chloroform, and propylene glycol; and insoluble in diethyl ether. Neutral and alkaline solutions are unstable; sensitive to oxidation and photo degradation.6,7,8 Molecular Weight9: 303.82638 [g/mol] Molecular Formula : C18H22ClNO MonoIsotopic Mass9: 303.138992 CAS-No. : 63-92-3 The stability studies for Phenoxybenzamine injection concentrate were carried out by Zeta Analytical Ltd. for their Clients. Also analytical method for related substance of Phenoxybenzamine Injection has been validated by them. During the stability studies, it has been found that some stability batches contain more than 0.1% of unknown impurities. Already there are three identified, process related impurities were reported in their clients analytical methods.10 Those three impurities A, B, and C are reported as shown below. 1. Impurity A: N-benzyl-N-(2-chloroethyl)-2-phenoxypropan-1-amine Fig. 02 Molecular structure of N-benzyl-N-(2-chloroethyl)-2- phenoxy-propan-1-amine 2. Impurity B: N-benzyl-N-(2, hydroxyethyl)-1-phenoxypropan-2-amine Fig. 03 Molecular structure of N-benzyl-N-(2-hydroxyethyl)-1-phenoxypropan-2-amine 3. Impurity C: N-(2-chloroethyl)-1-phenoxypropan-2-amine Fig. 04 Molecular structure a of N-(2-chloroethyl)-1-phenoxypropan-2-amine According to the International Conference on Harmonization1,2 (ICH) guidelines any component of a pharmaceutical product which is not the chemical entity of active substance or excipients, present at levels higher than 0.1% or 1 mg/day intake (whichever is lower) for a maximum daily dose of 2 g/day or less, need to be identified and qualified with appropriate toxicological studies. For a daily dose of greater than 2 g of drug substance, the identification threshold is 0.05%.1 ,2 Also British (BP), European (EP) and United states (USP) pharmacopeia texts refers the ICH criteria on impurity profiling for new drug substance and new drug products.5,6,7 Hyphenated techniques such as LC-MS and LC-NMR methods as an effective tool for characterization of impurities and degradation products in drug molecules. Therefore, Zeta Analytical proposed this project to perform LC-MS analysis on Phenoxybenzamine injection for structural elucidation of unknown impurity. This project involved method transferring (Tech transfer) from Zeta to Kingston University and developing a LC-MS compatible chromatographic method structural identifications of unknown impurity. Literature Study: There are no chromatographic methods have been reported in the literature describing the analysis of Phenoxybenzamine and its related substances using UV detection. The chromatographic Conditions mentioned in United States Pharmacopoeia (USP) monograph7 (refer Appendix) and Zetas method quiet similar apart from the detection wavelength, which is 268nm for USP and 220 nm for Zeta. Both methods are not compatible for LC/MS analysis. Because phosphate buffer is a one component that mobile phase consist in both methods. There are no reports available on the investigation using LC/MS/MS and isolation of related substances in Phenoxybenzamine active pharmaceutical ingredient (API). However, in order to analyse the sample in LC/MS and to get better chromatographic resolution the method has been modified for use in the present investigation. A synthesis route of Phenoxybenzamine has been mentioned in Vardanyan and Hruby,18 and slightly different route of synthesis for phenoxybenzaime related amines has been reported in Giardink et al.13 EXPERIMENTAL Material and Methods Chemicals used (all anal. Grade )were: Phenoxybenzamine Hydrochloride ( Sigma- Aldrich) , Impurity B (PBA) from med alchemy S.L Spain, HPLC grade Acetonitrile (Sigma- Aldrich), Potassium phosphate dibasic, Potassium phosphate monobasic, Ammonium formate, Ammonium Hydroxide, MilliQ grade water Samples Phenoxybenzamine injection concentrate ; Each 2 ml ampoule contains 100 mg Phenoxybenzamine Hydrochloride BP and excipients are absolute ethyl alcohol, hydrochloric acid AR and propylene glycol. Sample Preparation for HPLC and LC-MS Whole contents of ampoule was transferred to a 100mL volumetric flask and dissolved with 30 mL of acetonitrile. Then it was shacked for few minutes to mix well and added more acetonitrile to volume up the level of volumetric flask. HPLC analysis at Zeta Analytical Ltd. HPLC analysis was proceeded at these chromatographic condition : Column Phenomenex Gemeni-NX 5Â µm C18 110A 250-4.6 mm. Mobile phase used : pH 7.5 20mM Phosphate buffer (Dissolved 2.4g of K2HPO4 in 1L of water and adjusted to pH 7.5 with KH2PO4) : Acetonitrile = 30% : 70% (Isocratic mode ) .Column temperature 25C , flow rate 0.9 cm3min-1 , detection at 220nm . HPLC system used at Zeta analytical Ltd : Pump , Auto sampler ,UV detector and thermostat are Agilent 1100 series with Agilent Chemstation for LC data system. HPLC analysis at School of chemistry and pharmacy, Kingston University: HPLC analysis was proceeded at these chromatographic condition : Column Phenomenex Gemeni-NX 5Â µm C18 110A 250-4.6 mm. Mobile phase used : pH 7.5 20mM Phosphate buffer (Dissolved 2.4g of K2HPO4 in 1L of water and adjusted to pH 7.5 with KH2PO4) : Acetonitrile = 30% : 70% (Isocratic mode ) .Column temperature 25C , flow rate 0.9 cm3min-1 , detection at 220nm . HPLC system used at Kingston University: Pump , Auto sampler ,UV-VIS detector and thermostat are Perkin Elmer series 200 with Totalchrom v6.2 software. LC- MS analysis at School of chemistry and pharmacy, Kingston University: LC-MS analysis was proceeded at these chromatographic condition : Column Phenomenex Gemeni-NX 5Â µm C18 110A 250-4.6 mm. Mobile phase used : pH 8.3 20mM Ammonium formate buffer (Dissolved 1.3g of NH4HCO2 in 1L of water and adjusted to pH 8.3 with NH4OH) : Aceotonitrile = 30% : 70% (Isocratic mode) .Column temperature 25C , flow rate 0.9 cm3min-1 , detection at 220nm . LC system : Pump , Auto sampler ,UV-VIS detector and thermostat are Perkin Elmer series 200 with Totalchrom v6.2 data system. Mass detetectors used : Two different mass detectors were employed : Waters Micromass LCT ESI-TOF-MS system with Mass Lynx 4.1 software Thermo TSQ Quantum Access system ( MSMS ) with Thermo Excalibur software RESULTS AND DICUSSION HPLC Analysis at Zeta Analytical Ltd. Initially the sample was analyzed in Agilent HPLC in Zeta Analytical Ltd. Based on the Zetas Analytical Method validation report for the related substance of Phenoxybenzamine HCl injection, the three identified impurities and one unidentified impurity were confirmed. Below the fig.05 (Appendix A-1) shows the peaks of Phenoxybenzamine and its impurities and the table 01 shows the retention time of those peaks. Fig. 05 HPLC chromatograms of Phenoxybenzamine HCl injections Table 01: Peaks and its retention time of Phenoxybenzamine (zeta) Peaks Retention Time / min Impurity C 5.2 Impurity B 7.3 Unidentified Impurity 8.6 Impurity A 18.2 Phenoxybenzamine 19.6 HPLC Analysis at Kingston University: (Method Transfer) The above results obtained at zeta were replicated again with Perkin-Elmer HPLC system in Kingston University. Same chromatographic condition was employed with same Phenomenex Gemeni-NX 5Â µm C18 110A 250-4.6 mm column . The fig.06 below show chromatogram of Phenoxybenzamine HCl injection analysis repeated at Kingston University(Appendix A-2). The peaks were interested and its retention times are shown in the table 02 below. Fig.06 HPLC chromatogram of Phenoxybenzamine HCl Injection (Kingston) Table 02. Peaks and its retention time of Phenoxybenzamine (Kingston) Peaks Retention Time / min Impurity C 5.0 Impurity B 7.0 Unidentified Impurity 8.4 Impurity A 17.9 Phenoxybenzamine 19.5 LC-MS Analysis of Phenoxybenzamine Injection Concentrate: Phosphate buffers are not compatible for LC-MS due to their non volatile nature. Since it was necessary to replace the phosphate buffer to a volatile buffer. Mean while the chromatographic development should not be changed. The ammonium formate buffers are widely used in LC-MS analytical methods and has buffering pH range (8.2-10.2) close to the previous phosphate buffers used which is pH 7.5 . 20mM ammonium phosphate buffer was prepared adjusted the pH to 8.3. The HPLC analysis previously performed was repeated with mobile phase of Ammonium formate buffer : Acetonitrile =30: 70 instead of mobile phase of phosphate buffer : Acetonitrile = 30:70 . The isolation of peaks and the resolution obtained in previous analysis was replicated. Fig. 07 Show the HPLC chromatogram of replicated results with Ammonium formate buffer and the table 03 show retention time and its corresponding peaks. Fig.07 HPLC chromatogram of PBA Injection Sample ( Modified Mobile phase for LC-MS analysis) Table 03: Peaks and its retention time of Phenoxybenzamine (Ammonium formate as buffer)The samples were run on HPLC several times and constant chromatographic development was observed. Hence the sample fractions of unknown impurity was collected several time during HPLC run for LC-MS (accurate mass measurement) and LC-MS/MS (selective ion monitoring) analysis. Peaks Retention Time / min Impurity C 5.3 Impurity B 7.3 Unidentified Impurity 8.7 Impurity A 18.5 Phenoxybenzamine 19.8 Accurate mass measurement with Time of Flight (ToF) mass detector Feasibility of TOF mass detectors has made it to be used widely for measurement of accurate mass. Several unknown impurity sample fractions were analyzed for the accurate mass measurement on Waters micromass LCT ESI TOF-MS and obtained the average of the accurate mass value of unknown impurity. Ionization technique is Electron spray Ionization and mass analyzer is Time of Flight analyzer in this instrument. Results were taken on positive mode ( M + H + ). Hence mass of one proton must be deducted from the spectral mass value to obtain the exact mass value of unknown compound. H1 mass is considered to be 1.007 Da in the calculation below. Table 03: m/z value of Peaks observed its corresponding calculated monoisotopic mass M + H + / Da Mass of Unknown Compound / Da 344.215 343.208 344.216 343.209 344.216 343.209 344.219 343.212 344.211 343.204 344.209 343.202 344.215 343.208 344.214 343.207 344.215 343.208 344.213 343.206 344.215 343.208 344.22 343.213 344.213 343.206 344.221 343.214 344.223 343.216 The average molecular weight and standard deviation of results are found to be 343.2086667 and 0.003754363 respectively. Above results were subjected to statistical evaluation using Microsoft excel spread sheet. At 99% confidence level the molecular weight of the unknown impurity is found to be 343.2086667 0.002497. Determination of Elemental Composition of unknown impurity. Using Mass Lynx 4.1 MS data management software possible elemental composition was obtained for the molecular weight of 343.209 with 200.0 mDa tolerance . It was able to exclude a large amount elemental composition to narrow findings. That is elimination of Chlorine in the composition . Because the mass spectrum of unknown impurity does not show the isotopic pattern for chlorine. i.e. When one Chlorine atom is present in a molecule, that will show a n/n+2 ratio of 100/32.4 (35Cl/37Cl ratio of 100/32.4). 15,16 Hence only C,H,N and O elements were limited on search. Still hundreds of composition are left to be examined to find correct elemental composition . The second exclusion that is Nitrogen rule14 which was used to eliminate many of those composition. Since the unknown impurity molecular weight is odd number, we can eliminate all the composition with the even number of nitrogen in list. The following table shows considerable elemental composition left after above two exclusions . Table 04. Possible elemental composition and its Monoisotopic mass Elemental Composition Calculated Monoisotopic mass C12H25N9O3 343.2080 C16H29N3O5 343.2107 C23H25N3 343.2048 C21H29NO3 343.2147 C12H29N3O8 343.1955 C15H29N5O4 343.2220 C24H25NO 343.1936 The monoisotopic mass of main active compound is 303.14 and it contains 18 carbon on that molecule. Unknown impurity has the monoisotopic mass value 40 amu higher than the active compound. Therfore if it is been assumed that unknown impurity has more than 18 carbon on its molecule, only two elemental composition would be remained. i.e. C23H25N3 (343.2048) and C24H25NO (343.1936). LC -MS/MS (Tandem mass )Analysis of Phenoxybenzamine HCl Injection Concentrate Thermo TSQ Quantum Access LC-MS/MS was employed for the selective ion monitoring. The unknown impurity fractions , Phenoxybenzamine HCl standard (sigma ) and Impurity B standard were analysed. Analysis of Phenoxybenzamine HCl standard Parameter used: Parent mass: 304.4 Scan time: 0.5000 Collision energy: 16 Collision gas pressure: 1.1 Barr Spray Voltage: 4000 Scan Mode: Product Ion Scan Fig. 08 Product ion scan mass spectrum of Phenoxybenzamine Standard Peaks at m/z 63, 84, 91,107,120, 135 and 212 were observed. The base peak is observed at m/z 91 benzyl fragment . It is stabilized by the resonance form of benzene.17 The following figure illustrates the break downs and its corresponding mass units observed in the product ion scan spectrum. Fig. 09 Illustration of break downs of Phenoxybenzamine Apart from the peaks illustrated on above figure, the peaks at m/z 120 arise due to mass unit CH2NCH2CH2Cl + H+ . This is the middle portion after the mass unit at m/z 91 and 93 break apart from the whole Phenoxybenzamine molecule. i.e M + H+ the molecular ion is m/z 304, but 304 (91+93) = 120 . Analysis of Impurity B standard Parameter used: Parent mass: 286 Scan time: 0.5000 Collision energy: 16 Collision gas pressure: 1.1 Barr Spray Voltage: 4000 Scan Mode: Product Ion Scan Fig. 09 Product ion scan mass spectrum of Impurity B Standard Product Scan spectrum shows peaks at m/z 84, 91,102,107,135,178,194 and 285. The base peak is m/z 91and the molecular ion is m/z 286. The following figure illustrates the break downs and its corresponding mass units observed in the product ion scan spectrum. Fig. 09 Illustration of break downs of Impurity B As seen in the Phenoxybenzamine product ion scan spectrum the removal of mass units m/z 91 and 93 also is observed in this Impurity B spectrum. i.e . there is a peak arise at m/z 102 , this is due removal mass units m/z 91 and 93 from the molecular ion m/z 286. [286-(91+93)=102] Analysis of Unknown Impurity Parameter used: Parent mass: 286 Scan time: 0.5000 Collision energy: 16 Collision gas pressure: 1.1 Barr Spray Voltage: 4000 Scan Mode: Product Ion Scan Fig. 10 Product ion scan mass spectrum of Unknown Impurity Product ion Scan spectrum shows peaks at m/z 84,91,107,119,135,152,160,178,251,267 and 344 . Here the molecular ion peak and base peak are same at m/z 344. This mass spectrum shows quiet similar fragmentation pattern with Phenoxybenzamine and the impurity B were analysed before. Peaks at m/z 84, 91, 93, 107, and 135 are found in all three , Phenoxybenzamine , Impurity B and unknown impurity product ion scan spectrum. Also as studied previously in the spectrum of PBA and impurity B, the deduction of the mass units m/z 91 and 93 from the molecular ion (m/z 344) results a obvious sharp peak at m/z 160. From the facts studied above in product ion scan mass spectrum and accurate mass measurement for elemental composition using TOF -MS , It can be hypothesized a structure of the unknown impurity . The proposed structure for unknown impurity is shown below in figure. Fig. 11 The Molecular Structure proposed for unknown impurity, N-benzyl-N-[(E)-2-phenylethenyl] -1- phenoxy-propan-2-amine The proposed structure can be rationalized with the product ion mass spectrum of unknown impurity. Following fig.12 shows the break downs of the unknown impurity that correspond to the peaks observed on mass spectrum. Fig. 12 Illustration of break downs of Unknown Impurity Most of the impurities found in pharmaceutical compounds usually process-related compounds; they are most probably structurally similar to the synthesized target drugs. It is prominent to study the synthesis route of active pharmaceutical ingredient (API), when the unknown impurity of drugs substance is been identified. Unfortunately the original synthesis route followed by the API manufacturer of Phenoxybenzamine is not known. The prediction for synthesis route of Phenoxybenzamine with possibilities for arising of other 3 Identified process related impurities (A, B, and C) is shown in the following scheme below based on Giardink(1995).13 + (a) (ii) (iii) (iv) (b) (v) (c) (d) (vii) (vi) (a)Oxidation ;(b) 1-phenylmethanamine, HC1/EtOH,molecular sieves 4A, NaBH3CN; (c) Br(CH2)2OH, K2CO3, EtOH; (d) SOCI 2, HCI (g), Benzene (i)phenol; (2)2-methyl oxirane ;(3)1-phenoxypropan-2-ol;(4) 1-phenoxypropan-2-one; (5) N-benzyl-1-phenoxypropan-2-amine; (6) 2-[benzyl(1-phenoxypropan-2-yl)amino]ethanol;(7) N-benzyl-N-(2-chloroethyl)-1-phenoxypropan-2-amine (Phenoxybenzamine) Scheme 1. Predicted synthesis route for Phenoxybenzamine Formation of Impurity A The reaction between phenol (i) and 2-methyl oxirane (ii) is SN2 nucleophilic substitution. Nucleophiles are more reactive to most substituted carbon of epoxides under acidic condition and least substituted carbon is favoured under basic condition.19 In this case carbon position 2 (fig.13) is favoured under basic condition and its form 1-phenoxypropan-2-ol ,which is the precursor molecule for PBA . Fig. 13 Structure of 2-methyl oxirane To very few extent the nucleophiles react at carbon position 3 will form 2-phenoxypropan-1-ol, which will lead to the formation of Impurity A along synthesis process of PBA. Fig.14 Structure of 2-phenoxypropan-1-ol Formation of Impurity B and Impurity C Impurity B, 2-[benzyl(1-phenoxypropan-2-yl)amino]ethanol is intermediate product during synthesis. Refer structure (vi) of scheme 01 . Impurity C, N-(2-chloroethyl)-1-phenoxypropan-2-amine formed due to chlorination of intermediate product 1-phenoxypropan-2-ol (refer structure (iii) of scheme 01). The unoxidised 1-phenoxypropan-2-ol left over is chlorinated by SOCI 2, HCI during last step of the synthesis. Refer (d) of the scheme. CONCLUSIONS Preliminary structural assignments for unknown impurity of Phenoxybenzamine Injection were made on the basis of mass spectral data. Initially the works started with transferring HPLC method from Zeta Lab to Kingston university and developing a LC-MS chromatographic method. Ammonium formate volatile buffer was replaced for phosphate buffer in HPLC method . Same chromatographic development was able to replicated with ammonium formate buffer. Accurate mass measurement was carried out on ESI-TOF LC-MS . Also this studies led to determine possible empirical formula . Then LC-MS/MS analysis was performed. The Product ion Scan mass spectral data are very vital information in final structural elucidation of unknown impurity. The structure deduced from MS/MS confirms the empirical formula C24H25NO that derived with LC-TOF-MS spectral data. Eventually the impurity identified in this this preliminary structural assignments , which eluted at retention time of 8.7 minute was predicted as N-benzyl-N-[(E)-2-phenylethenyl] -1- phenoxy-propan-2-amine . The proposed molecular structure for unknown impurity is shown in fig.11 . The formation of impurities A, B and C those had already identified by manufacture were described based on the predicted synthesis route for Phenoxybenzamine . The formation unknown impurity was not able to explained at this stage of this project since the reaction would have occurred found to be more complicated. This project work was wrapped up at this stage due to time limitation. Further to these preliminary structural assignments various spectroscopic studies such as LC-NMR and IR need to be carried out to complete the characterization of the unknown compound. Ultimately the proposed st ructure can be confirmed by synthesizing N-benzyl-N-[(E)-2-phenylethenyl] -1- phenoxy-propan-2-amine in future.

Sylvia Plath Essay -- Sylvia Plath Biography Biographies Essays

Sylvia Plath was a gifted writer, poet and verbal artist whose personal anguish and torment visibly manifested itself in her work. Much of her angst stems from her warped relationship with her father. Other factors that influenced her works were her strained views of human sexuality, her sado-masochistic tendencies, self-hatred and her traditional upbringing. She was labeled as a confessional poet and biographical and historical material is absolutely necessary to understand her work. Syliva Plath was born on 27, 1963, in Boston, Massachusetts to Otto Emil Plath and Aurelia Schober. Otto Plath was a professor of biology and German at Boston University. He was of German descent and had emigrated from Grabow when he was fifteen. Her mother was a first generation American; she was born in Boston to Austrian parents. Their common Germanic background indirectly led to their meeting in 1929. Aurelia Schober took a German class taught by Otto Plath. Aurelia was working on a master’s degree in English and German at Bosto n University. Otto Plath was guided by his principles of discipline. Their background was one major source of for Sylvia’s poetic imagery. Sylvia’s brother, Warren, was born on April 27, 1935. After Warren’s birth, the family moved to Winthrop, Massachusetts just east of Boston. Otto’s health began to fail shortly after Warren’s birth. He thought he had cancer as a friend of his, with similar symptoms, had recently lost a battle with lung cancer. â€Å"He refused to seek medical care due to the lack of a cure or effective treatment at that time. In 1940 after suffering ill health for years, Otto was forced to see a doctor for an infection in his foot. The doctor diagnosed the illness Otto has been suffering from as not cancer, but diabetes- -and not do advanced that it threatened his life. Otto’s leg had to be removed in October after he developed gangrene, and he spent the rest of his days in the hospital rapidly declining.† (Nuerotic Poets) Otto Plath died on the night of November 5, 1940. Her fathers’s death scarred her permanently; theirs was an extraordinarily close relationship. In 1942, Aurelia moved the family to Wellesley so that she could return to work despite her own health problems to support her family. Sylvia began writing when she was only five years old. Her first publication was a short couplet she wrote when she was eigh... ...hould be able to control and manipulate experiences even the most terrifying, like madness, being tortured, this sort of experience, and one should be able to manipulate these experiences with an informed and intelligent mind†¦.† (Uroff 37) Plath’s work is valuable for its ability to reach today’s reader, because of its concern with the real problems of our culture. In this age of gender conflicts, broken families, and economic inequities, Plath’s forthright language speaks loudly about the anger of being both betrayed and powerless. She was hailed as literary symbol of the women’s rights movement and a feminist writer of great significance. Sylvia Plath began by creating art that imitated life, but ended when life imitated art. Works Cited Butscher, Edward, ed. with and introduction. Sylvia Plath: the woman and the work. New York: Dodd, Mead, 1977. Plath, Sylvia. The Journals of Sylvia Plath. Ed. Ted Hughes and Frances McCullough. New York: Ballantine Books, 1982. Sylvia Plath. Ed. Brenda C Mondragon. n.d. Web. 18 May 2015. http://www.neuroticpoets.com/plath/ Uroff, Margaret Dickie. Sylvia Plath and Ted Hughes. Urbana: University of Illinois Press, 1979.