Moore Medical Corporation Free Essays

Q1.   Today people start new business ventures with different expectations than it was to be in the past.   As many techniques, ways and means of dealing with customers have also changed. We will write a custom essay sample on Moore Medical Corporation or any similar topic only for you Order Now    The new technology to many people has brought a lot of significant changes in the global business environment.   All the business sectors including private and government sectors are currently doing reengineering on how businesses are operated.   This is happening because of the new information and communication technologies.   Different companies are coming up with various types of new information system.   . For the case of Moore Medical co-operation the customer relationship management software may be purchased to meet its objectives.   What is important for the success of any organization is whether its objectives are met in the long run.   The problem Moore is facing is to find a new technology to service its customers better, to generate new business and to give employees the tools to handle a growing number of customer communications, more efficiently and effectively. I therefore suggest that the customer relations management software (CRM) or technology will ensure that customers are served well.   Production will never be high if customers are not served well or attracted.   The way customers are handled will determine the success of the business. The CRM technology will therefore improve customer interaction consistence between the economy and its customers. Q2.   Most companies have failed to realize the finical benefits because of poor financial evaluation of what is being purchased.   Financial evaluation comprise of knowing the value of what is being purchased.   Disappointing results have been gotten because the cost of installing most of the new technologies are highly than the benefits that it will create at the end of the financial year. Financial benefits of any item can be evaluated. For example Moore medical cooperation can assess its financial benefits of the proposed technology.   One way is by analyzing the number of customers that are making orders using the new technology.   If the number of customers using the new technology is high then the new technology introduced is favorable to the company.   Another way through which the financial benefits can be assed is by comparing the installation cost, training cost, implementation cost with the sales that is obtained from the use of the new technology. It is obvious that implementation of the software’s will need some money.   Those who will be at the customer service department will also be trained.   So any cost associated with the introduction of the new system should be recorded down then compared with the sales obtained after the new system has been put into place.   This will determine if the company will be making profits or losses as a result of introducing the new technology. Q3.The success of any business or organization will depend on it quality of customer service skills employees working in customer service department possess.   Moore Medical Corporation has not been left behind.   The company is considering purchasing customer relationship management software with an objective of improving the ways of responding to customer desires. The CRM software will ensue that customer orders are not delayed.   The new technology (CRM) to Moore would increase or attract more customers and even maintain and keep the already existing ones. The number of customers a company serves normally determines the sales that the company will get.   Production rate would also increase by fixing the new technology in the system The new information and communication technology has changed the way businesses are done in the business environment.   Customers nowadays want maximum satisfaction from the company managers and front-line employees serving them.   Without new IT there is nothing that can be improved in any organization.   Performance and quality of products in any organization will only increase if the use of new information technology is implemented.   Goods will be delivered in time, customers will be served effectively and efficiently ensuring that they are fully satisfied.   New business and products have also been created in the environment as a result of the introduction of the new technology. Among the business needs Moore is hoping to address with this new information technology include the following.   They want to improve sales forecasting.   They also want to reduce the number of sales representatives and reduce time to attend to customers.   The new information will also increase the accuracy and accessibility of the information obtained from customers.   The other business needs that will be addressed by the new technology are to increase rep effectiveness and efficiency and finally to increase the customer interaction consistency among all representatives by increasing company control and manner of customer interaction. Q4.Training is one of the most business practices that any company should do whenever any new technology is introduced in a company.   All organization members need training to acquire new skills and knowledge for the production to be increased and effective. Training should provide essential information on the department / program. If the company uses new technology, the supervisor of that particular company needs to train the employees on how to use the software introduced. For the case of Moore medical cooperation, training its customer’s service representation on how to use the information technology that is the customer relations management software was ignored.   For example it was realized that the customers service representative found the order entry system in J.D. Edwards difficult to use in comparison to their old system.   The new account set up process within J.D Edwards also added time to customer calls.   It therefore means that customer needs and interest would be lowered.   When the way they are served is sluggish then there is a possibility that the company may lose them. Effective communication is another area where the Moore Company has failed to adopt.   Actually when changes are created in an organization, the management or human resource manager should ensure that the change is communicated to all the groups served by the organization (Satzinger, 2004). Effective communication is one of the key issues that the organization should know about its customers.   All members in any organization including employees, customers and suppliers have different cultural background.   The Moore should therefore consider the customers’ practices, likes, interest, belief and values.   After considering all these elements of culture the organization will then be in a position of making a good decision whether the new technology will work or fail.   In short the Moore manager should know about the cultural background of its customers to identify whether they will like the new technology created (Satzinger, 2004). Q5.The use of the new information and communication technology has created numerous changes in the global market and in companies dealing in electronic commerce.   New businesses have been created in the environment while old ones have been transformed. New business models have been formed that would that would have been unthinkable for years back.   However there are advantages and disadvantages that have resulted from the introduction of computer software. Moore move into E-commerce with an intention of improving customer service might result into same advantages and disadvantages.   For first the advantages are numerous.   If properly implemented the new system will automatically serve its customers better.   By improving customer Service, it means that the sales and production will also increase. Production in any organization will be determined by the number of customers it serves.   If more customers are attracted then it means that the profit or the financial benefits that the company wants to achieve will also be high.   The CRM software will therefore help Moore cooperation to realize high financial benefits. Service delivery by increasing the number of orders taken from customers will also increase While the advantages are visible, there are some negative outcomes that Moore might get by moving into E-commerce.   Culture of the customers might actually influence and determine whether the new system will be successful or not.   Some customer may refuse to make orders using the new system introduced in the organization.   This may lead to the failure of the system leading to a big loss to the company.   When customers refuse to use the new system then they will be lost leading to decreased sales. Customers might refuse to use the new system just may be because they are no informed in time or poor communication.   They may also just refuse due to differences in cultural background.   Therefore this is an important factor that might lead to the failure of the new system. The cost of implementation may also be too high for the company to realize the financial benefits it wants to meet.   It might decide to use the new system without financial evaluation, which is very important.   This may also lead to the failure of the company. Reference Sat Zinger, J. (2004). Systems analysis and Design in a changing world.   London: Thompson publishers. How to cite Moore Medical Corporation, Essay examples

Fuguland free essay sample

The people of fugawiland are composed of at least two different cultures. They are characterized by the type of pottery that they used and the shape of their houses. The eastern culture used the banded pottery and constructed the square huts. They also utilized the resources of chert. The reason is the location of the chert. The western culture used the zig zag pottery and constructed round huts. They were all hunters and gatherers utilizing the time seasons and game for that time. White tail deer was hunted in the fall season. The rabbit had the largest season which started in the summer and extended to the early winter. The lake trout was plentiful during the spring and fall season, while fresh water mussles were only available in the spring. Acorns, were available in the fall. There were four principle groups of sites used by the people. The groups were the shore sites, river sights, mountain areas, and the plains. We will write a custom essay sample on Fuguland or any similar topic specifically for you Do Not WasteYour Time HIRE WRITER Only 13.90 / page The shore groups had light huts. The river sites used heavy huts. The mountain sites were used only for a short period of time due to the weather conditions. The plains were the holy burial grounds during the warmer months the tribes would bury their dead that had collected over the freezing months. Trading existed among the tribes in a very small amount. A small amount of chert was found in the copper side burial grounds while a small amount of copper was found among the burial of the people with the chert. Chert and Copper were a means of trade and possible used for weapons. However it seems that only chert and copper was traded across the boundary of culture. The houses did not change and neither did the pottery. Fugawiland huts contained approximately five people. The artifacts highest concentration was around the hearths. These people were hunters and gathers. The women were the homemakers, the cookers and cleaners, while the men were the hunters. The community worked together as a whole and survived as a tribe. Most of the people come from the southern river valleys and migrated up to the North for the fish. These people had a very successful lifestyle for many years.

Fanfare for the common man free essay sample

The piece was written in 1942 for the Cincinnati Symphony Orchestra under conductor Eugene Sessions. It was inspired in part by a famous speech made earlier in the same ear where vice president Henry A. I couldnt relate to this piece, it didnt resonate with me. Burlier Symphonies fantastical IV ( March to the scaffold) This piece reminds me of marching band at high school pep rally. The sound of the timpani also reminders heavy footsteps of an army. The song starts quietly, with the illume getting louder progressively as the solos start and the tempo is kept the same for the majority of the song. The song gets extremely warm and loud towards the end. The cymbals would sure wake you up! Great piece. The sunken Cathedral Debussy places the title of the piece at the end of the piece, to allow the pianist to respond individually to the music. We will write a custom essay sample on Fanfare for the common man or any similar topic specifically for you Do Not WasteYour Time HIRE WRITER Only 13.90 / page This piece is based on a legend. The first chord of the piece is made up of sonorous as and Ads. It was published in 1910 as the tenth prelude in Debussy first of two volumes of twelve piano preludes each. I loved this piece only because its a piano, soft melody that I felt I could Just fall asleep to. Afro American Symphony The first symphony, written by an African American man, and performed for an American audience by a leading orchestra. It was premiered in 1931 by the Rochester Philharmonic Orchestra. It Is a full orchestra, Including Celeste, harp, and tenor banjo. This piece reminds me of old western movies, Its upbeat and fun I loved listening to it, although it wasnt required I listened to the entire symphony.I also can appreciate it because as an African American, this piece was written during the Harlem renaissance at the heart of an awakening In our society. Rhapsody In blue This was written by George Gershwin, this piece Is for solo Plano and Jazz band, which combines elements of classical music with Jazz-Influenced effects. Rhapsody In Blue displays both rhythmic Invention and melodic Inspiration. The piece begins and ends In B flat. Serge profile symphony no. 1 This piece Is a neoclassical composition.This kind of music and sound are new to me. Im glad I was exposed to It, this was a new learning experience. Although, Im still not sure If I enjoyed the piece, I will Like to hear more from this genre to familiarize myself to It. Fanfare for the common man By loveliness Philharmonic Orchestra. It is a full orchestra, including Celeste, harp, and tenor banjo. This piece reminds me of old western movies, its upbeat and fun I loved Harlem renaissance at the heart of an awakening in our society. Rhapsody in blueThis was written by George Gershwin, this piece is for solo piano and Jazz band, which combines elements of classical music with Jazz-influenced effects. Rhapsody in Blue displays both rhythmic invention and melodic inspiration. The piece begins and ends in B flat. Sergei profile symphony no. 1 This piece is a neoclassical composition. This kind of music and sound are new to me. Im glad I was exposed to it, this was a new learning experience. Although, Im still not sure if I enjoyed the piece, I will like to hear more from this genre to familiarize myself to it.

Exploring The New Testament Volume 1 Analysis Religion Essay Example

Exploring The New Testament Volume 1 Analysis Religion Essay Example Exploring The New Testament Volume 1 Analysis Religion Essay Exploring The New Testament Volume 1 Analysis Religion Essay The book, Researching the New Testament by Wenham, David A ; Walton is the first book in a series of six text editions which covers the Old and New Testament, the Gospels and Acts. Teachers with extended experience who instructed pupils in their first two old ages of university degree survey wrote the book. The intent of the writer s was, for the most portion, to compose a book in a concise and apprehensible mode to acquire pupils and every twenty-four hours reader s to be, and acquire connected with the Gospels and Acts for themselves, more than merely larning, from what these books affirmed or simply soaking-up a batch of appealing theories about them. Therefore, in some chapters of the book the author have made an attempt to provide equal mentions to the Gospels and Acts, and other important antique text, so that the reader s can read the texts together with the treatment. Besides, with three more types of extra survey where pupils can follow many of which are written in the book. Diging Deeper The book offers a subdivision called Digging Deeper, these boxes offer a spots of research of between 2-3 hours of personal survey, or it can besides be used as a one-hour category room group treatment led by the teacher or by pupil. By including two or three pupils to take such a treatment, the author says, in our experience, enables pupil leaders to prosecute with the subject at greater deepness, given that, the pupils have to put the agenda for the group treatment, every bit good, let the pupils to discourse positions with each other in a manner that aid acquisition. And offer suggestion how a group treatment clip might be prearranged to manage the subject. Essay Subjects In the book, at the terminal of each chapter offer thoughts on essay subjects, which are required to be hand-in, in composing. They were aimed to be around 2,500 3,000 words in length, some of the subjects are classified as preliminary and are proposed for first twelvemonth scholars, while, others as intermediary for 2nd old ages scholars. The authors of the book suggested, since there are legion subjects to be done the teacher should choose those subjects which best fits the exact agencies and intents of the class being taught, and to direct pupils to do the best choice of which to follow. The book encourages farther reading recorded at the terminal of each chapter, books selected within European and North American college and university libraries which in general, accessible. Inside every chapter the writer referred to drop the ball by and day of the month system e.g. Wright 1996, and full publication inside informations can be found in the farther reading subdivisions. Where a book has a British and an American edition, we have endeavored to supply topographic point of publication and publishing house for both editions. Sporadic Section I was struck by the penetration into mundane Christians populating that these writers had expressed, and the mentions they made to their ain belief in Christ. For that ground, they have made available sporadic section depicting a figure of issues for today life, which outline several of the Christian belief in the surveies. These section are intended to be leaping off tips and illustration to back up pupils and teachers to do their ain confederation and associating at that juncture, and at the minute. The writer s assumed that a batch of pupils which are analyzing the Gospels and Acts are Christians, hence, would wish to inquire inquiries about the significance of the surveies to populating as a Christian today. The Structure of the book separated into five parts, foremost, the tabular array of contents, which is nicely elaborate, dwelling of chronological and context of Jesus and the New Testament, faith, the life of Jesus in the visible radiation of history, the instruction and purposes of Jesus, the life Jesus live which the early churches should pattern. The book focal point on the Judaic contents ; Judaism in first-century Palestine ; parties and group within first-century Judaism, Pharisees, Sadducees, Essens, the 4th doctrine, and the revolutionists. The comrade volume on the NT letters and Revelation will put the Graeco-Roman content, which is more relevant to those NT books. The 2nd portion lineation techniques of survey on the Gospels, such as, what are the Gospels ; where did the Gospels come from ; understanding the Gospels today ; the Gospels as unlike other ancient literature, and why were the Gospels written. The Gospels focuses on the most of import individual, Jesus the Messiah. His birth and beginnings ; his miracles, why did he died ; Jesus reaching in Jerusalem ; Jesus moralss and his position of the Torah ; who did Jesus believe he was ; and Jesus and the land of God. The book spotlights each of the Gospels get downing first with Mark. Harmonizing to the writer s since Mark has fewer chapters than the other three, and seems to be the first was written. The author s say, This allows Matthew and Luke to concentrate on the typical parts of these Gospels. Whereas, the book of John is comparatively drawn-out, for the ground, that John theatrical production of Jesus is unusual from the others in his authorship manner. Each one of the chapter looks at the major building, topics, and accent, of the Gospels, with a concise contemplation of who wrote each book when, and why. Decision The concluding portion is the learning on Acts, with the transfer of the narrative of early Christianity. It looks on Acts as Luke s volume two ; what sort of book it is, and its manner and presentation ; Acts and history, and divinity, some major subjects on God, Jesus, the Holy Spirit mission and the church ; writing and day of the month. A glossary at the terminal provides mention to the chief topographic points in our book where cardinal proficient footings and words are introduced and explained, peculiarly in boxes within the chapters. I like the book, it is really utile I am trusting to buy a transcript, it is to the point, deserving reading, and even deserving analyzing ; it has an abundant of information on assorted topics that are first-class, non merely in remarks, but provide a host of good thought out and good presented thoughts, and it is low-cost.

Business research literary review on action research Essay

Business research literary review on action research - Essay Example The sequence of steps includes â€Å"once scenario is studied: a corrective plan is determined, planned and implemented; results of the action are observed and recorded; and the action is assess as effective or not† (Cooper & Schlinder, 2011). This literature review will take a journey through the foundations of action research, cases using action research and opportunities opened because of action research. Foundations of Action Research: Stephens, J., Barton, J., & Haslett, T. (2009). Action Research: Its History and Relationship to Scientific Methodology. Systemic Practice & Action Research, 22(6), 463-474. doi:10.1007/s11213-009-9147-7 As it has been discussed briefly in the introduction, action research is a method of research that seeks to address practical problems. In such a way, it oftentimes deviates from the standard approach in which the scientific method seeks to identify an issue, theorize with regards to a solution, and/or measure whether or not such a theory is relevant and pertinent. Ultimately, this key level of deviation is one of the core compliments of why action research came to be born out of the already working processes of the scientific method. Stevens et al. ... The authors indicate that these drawbacks are concentric around whether or not the idea is more driven from the researcher’s agenda or more driven from the participants; whether or not individuals are motivated by an instrumental goal of whether or not a narrow level of focus skews the research results with regards to applying it to a larger test group or situation. Naturally, this is not to say that action research is inherently flawed; rather, it merely denotes the fact that it holds a level of benefit as well as a level of difficulties as compared to traditional scientific methodological research. Boog, B. M. (2003). The emancipatory character of action research, its history and the present state of the art. Journal Of Community & Applied Social Psychology, 13(6), 426-438. Many researchers have underscored the fact that from the very beginning action research has been intended to be an emancipatory style. Compared to traditional scientific methodological research, action re search is something of a free-form and evolutionary style that allows participants to engage in a double-sided process of research. Moreover, due to the fact that the relationship between the researcher and the subjects is so critical with regards to developing a key level of inference and/or determinacy, Boog (2003) notes that the evolving character of action research demands a high level of emphasis be placed upon the approach with which the researcher engages the participants. Although Boog argues that this is not a new construct of action research, he also denotes the fact that without a type of constraining influence, the evolutionary history that has thus far been exhibited with regards to action research will ultimately transform it into an unrecognizable entity. As a direct

How the marketing of services differs from the marketing of products Essay

How the marketing of services differs from the marketing of products - Essay Example How the marketing of services differs from the marketing of products? When conducting the marketing of services, it is vital to depict the processes and proof of the service so that customers can have a positive image about the reliability of the services. Positive images and expectations allow the element of perceived value to be built in the consumer’s mind. In marketing products, there is no proof required as the product is something tangible that can be analyzed before buying and has the option of being returned if customers are not satisfied with it. For products, customers may be willing to pay a price before even viewing the actual price and this is based on the value perceived by the customer for the product. In products marketing, the price and benefits of the product is stated in the advertisement. In services marketing, it should be ensured to the customer that the service would be consistent and is going to meet the needs of the customer. Then the customer develops the perceived value for the service. Product pricing includes the material cost, the cost of distribution and the cost of manufacturing. The pricing of services include cost of offsite manufacturing and the traveling cost can be included if implied. The low cost in service pricing allows the firms to invest more in the service advertisements. In marketing the products and services, the place element of the marketing mix depends upon the type of products and services being offered. The products sold in retail outlets need to be in convenient location for the customers. For services, the place may not matter to the consumers.

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.