Comparative in-vitro Quality Evaluation of Cephalexin

Comparative in-vitro Quality Evaluation of Cephalexin A COMPARATIVE IN-VITRO QUALITY EVALUATION OF DIFFERENT BRANDS OF COMMERCIALLY AVAILABLE CEPHALEXIN IN KARACHI (PAKISTAN) SHAHBAZ AHMED NOOR Abstract: Approximately 600 generic drug applications (ANDAs) approved each year, 65 % of prescriptions are for generic indication from oncology to insomnia without repeating clinical trials .Every generic molecule references a previously approved drug. Cephalexin Monohydrates was first sold by Eli Lilly in 1972. The availability of many brands of cephalexin 500 mg capsules in Pakistan market today place healthcare providers in a difficult situation of choice of a suitable brand or alternate use possibility .The objectives of this study was to carry out pharmaceutical equivalence studies on different brands of cephalexin 500mg capsules available in local market of Karachi. The invitro parameters include all pharmacopeia and non-pharmacopeia tests that were dissolution rate( in 0.1 N Hydrochloric Acid at 37 à ¢Ã‚ Ã‚ °C ) ,weight uniformity , disintegration time , moisture content ( with the help of suitable Karl Fischer Titrator ) , appearance (observed physically before and after opening of the shell) , Identification ( compare manually retention time in HPLC chromatogram of sample with chromatogram of reference standard ) and HPLC assay of cephalexin (as describe below based on HPLC assay method AM1172) were also analyzed. Along with the inappropriate use of antimicrobials drugs, substandard antibiotic medicines may also contribute in resistance development against susceptible organism. The study will be helpful to evaluate the efficacy and justification of generic substitution of cephalexin 500 mg capsule brands in Karachi (Pakistan) INTRODUCTION: Antibiotic, being the wonder drugs, are widely prescribed in the developing countries. In reality, 25 to 40 % prescriptions contain one or more antibiotic (Public Sector studies, 1990-1993) Antibiotic resistance can be developed through its wide and inappropriate use without following any standard guidelines. This Alarming situation has been addressed in several scientific journals (Glass et al.,1980; Farrar , 1985; Saha et al., 2003;Lina et al.,2007;Hassan et al.,2009) Post –marketing surveillance include complete procedures undertaken to obtain more data and information about a product after it had been granted marketing authorization and made available for public use, this data used for product improvement ,development standard and regulations. Regulatory agencies rely on limited information get from clinical trials and from scientific literature as guide to granting to marketing authorization of medicine for public use. Post-marketing surveillance of approved dosage forms is to assess the quality, effectiveness and safe use of medicine to large population. To Assess the standard of a product, invitro dissolution test is widely used because , for any solid dosage forms, gastrointestinal absorption first requires dissolution of the tablet or capsules that librates the drug into solution (Goodman Gilman`s –The Pharmacology basis of Therapeutics,2006) The dissolution characteristics of a drug from the dosage form depend on many factors including its formulation and manufacturing process (Augsburger et al., 1983). Cephalexin Chemically, Cephalexin is {(6R, 7R)-7-[(R)-2-Amino-2-Phenylacetamido]-3-Methyl-8-oxo-5-thia-1-azabicyclo [4.2.0] oct-2-ene-2-carboxylic acid monohydrate} is a first generation cephalosporins for oral administration which is bactericidal, and mainly used in the treatment of various bacterial infections caused by gram +ve and gram -ve microorganisms. .( Ralph R et.al 1970).Excellent oral absorption and lack of serum binding of cephalexin compensates significantly for the lower in vitro activity.( Warren E. Wick et.al 1967). Antibacterial Spectrum of Cephalexin: Cephalexin appears to be a highly effective antibiotic. It possesses the qualities of rapid oral absorption, production of high drug levels in the blood and urine, and near absence of side effects. It is effective against infections due to gram-positive cocci infections, with the exception of Enterococcus, and for most infections caused by E. coli and Klebsiella. It is useful in the treatment of a wide variety of infections in infants and children, and particularly valuable with susceptible infections in patients who do not require parenteral antimicrobial therapy. (R.C. Rudoy, M.D.1977) The first-generation cephalosporins, epitomized by cephalothin and cefazolin, have good activity against gram-positive bacteria and relatively modest activity against gram-negative microorganisms. Most gram-positive cocci (with the exception of enterococci, methicillin-resistant S. aureus, and S. epidermidis) are susceptible. Most oral cavity anaerobes are sensitive, but the B. fragilis group is resistant. Activity against Moraxella catarrhalis, E. coli, K. pneumoniae, and P. mirabilis is good (Goodman Gilman`s –The Pharmacology basis of Therapeutics,2006) Literature Survey: A ) Helio et.al in 2007 In this study, they observed the antibacterial spectrum of the orally prescribe cephalosporin (cefaclor, cefdinir, cefpodoxime, cefprozil, cefuroxime axetil, cephalexin) and amoxicillin/clavulanate, as these drugs were widely prescribed for community acquired respiratory tract infections. Narrowest zone was of Cefaclor and Cephalexin against evaluated pathogens. Overall, the 3rd Generation of cephalosporin is more useful in respiratory tracts and other infections when administered orally, as compared with older generation or amoxicillin alone. B ) Chalermporn et.al in 2005 ,they studied for rapid and sensitive identification of cephalosporins drugs such as cefoxitin , cefazolin , cephalexin, cefadroxil , cefaclor and cefoperazone, a flow injection (FI) method was used. This method was applied successfully for the identification of cefoxitin, cefazolin, cephalexin, cefadroxil , cefaclor and cefoperazone. The method was successfully applicable for the identification of cefoxitin ,cefazolin , cephalexin and cefadroxil in the pharmaceutical formulation with a sample throughput of 90h−1. C ) Rist et.al in 2002, they studied on Oral Cephalexin compared with mupirocin calcium cream with respect to safety and efficacy in secondarily infected eczema treatment. The adverse effect most common , they observed was diarrhea and nausea, effective clinical dose of mupirocin cream was apply three times daily as compared to cephalexin orally four times daily in secondarily infected eczma as topical regimen was preferred by the patient that enhance patient compliance. D ) Lennart Venemalm et.al in 2001, worked for the diagnosis of allergy against ÃŽ ²-lactams, prazinone-polylysine conjugate was able to bind with antibodies IgE in sera from patient with suspected allergy to cephalosporin’s. This information may be used for diagnosis of allergy against ÃŽ ²-lactams. E ) Yagnesh P. Patel et.al in 1998 They studied, modern data on the isocratic assay of five antimicrobial drugs ,five different assay were performed to one single report, antibiotic used in this study were cephalexin and cefaclor (cephalosporin’s), isoniazid and pyrazinamide (anti-tubercular drugs) and minocycline (tetracycline series) . Overall they concluded that any one of the drug could be used as internal standard for other four drugs. F ) Godfried Owusu-Ababio et.al in 1995 Sustained release of cephalexin ciprofloxacin, was evaluated in open chemostat sytem. They concluded that chemostat system is convenient for sustained release drug testing as a function of formulation parameter. G ) Anne H. et.al in 1992 In this study, the Cefaclor uptake was observed concluded that it was sodium-independent, but proton-dependent and also the energy dependent , dipeptides inhibited uptake of ÃŽ ²-lactam antibiotic but amino acid had no effect on uptake , the overall data from this study concluded that a single proton-dependent dipeptide transport carrier support the orally absorbed antibiotic uptake into Caco-2 cell shows correlation for the use of Caco-2 cell for cellular model of the intestinal proton-dependent dipeptides transporters for study purpose. H ) R. Wise et.al in 1991 Cefibuten, invitro activity was studied against 572 bacterial strain and was compared with orally administered ÃŽ ²-lactams. Cefibuten being more active against Enterobacteriaceae. There was less activity of cefibuten cefexime against Staphylococci and reduce activity against streptococcus pneumonia. I ) Luis J et.al in 1982 They studied, Acid degradation of cephalexin in presence of formaldehyde, produce 2-Hydroxy-3-phenyl-6-methylpyrazine.In 5M HCL this product gives well defined reduction wavelength with half wave potential of -0.45 vs. SCE. The wave was diffusion –controlled irreversible, linear relation with the cephalexin conc. was shown with diffusion current and cephalexin in plasma can be determined through it. J ) Ralph R et.al in 1970 They performed to detect various crystal forms of compounds, the employment of solubility versus solvent composition diagram. This appears to be a convenient sensitive method for detecting new crystalline phase. Aim of Project: The objective of this study is to carry out pharmaceutical equivalence studies on different brands of cephalexin 500mg capsules available in local market of Karachi. The invitro parameters include all pharmacopeia and non-pharmacopeia tests that are dissolution rate, weight uniformity, disintegration time, moisture content, appearance, Identification and HPLC assay of cephalexin will also be analyzed. The susceptibility test of drug will also be evaluate by ICLS ( Formerly NCCLS ) Reference Disk Diffusion (Kirby-Bauer) method against different clinical isolates of Staphylococcus aureus (03), E. coli (03), Klebsiella pneumonia (03), Pseudomonas aeruginosa (02), Importance of study: This is a growing concern that if a health care provider, providing the substitute of the generic is also the Bioequivalent. For the health care providers to use these brands interchangeable, the bioequivalence of these brands have to be ascertained, this mean that there should be continued post marketing monitoring of the medicines. EXPERIMENT: TESTING PROCEDURE: Test # 1: Cephalexin Monohydrate (As base): Procedure: Perform HPLC assay of Cephalexin as describe below based on HPLC assay method AM1172. Test # 2: Identification: Procedure: Compare manually retention time in HPLC chromatograms of sample with chromatograms of reference standards. Test # 3: Moisture Content: Procedure: Three times separately the moisture content in the powder of the product with the help of suitable Karl Fischer Titrator will be determine and then calculate their mean. Test # 4: Appearance: Procedure: From the 20 capsules take 10 capsules and observe physically before and after opening of the shells. Test # 5: Weight Variation: From 20 capsules take 10 random capsules from composite sample and note individual weight of filled capsules. Calculate their average, minimum, maximum and COV%. Test # 6: Disintegration: Procedure: Prepare a 0.6% v/v solution of HCl (Add carefully 16.2ml of 37% HCl into 500ml of distilled water and then make the solution up to 1000ml with distilled water) and fill the vessel of a suitable disintegration test apparatus with this solution up to recommended height. Maintain the temperature between 35  °C and 39  °C. Place 1 capsule in each of the 6 tubes of the basket and run the equipment. Start the stopwatch and note the time when all capsules are disintegrated. If 1 or 2 capsules fail to disintegrate, repeat the test on 12 additional capsules. The requirements of the test are met if not less than 16 of the 18 capsules tested have disintegrated. Test # 7: Dissolution: Procedure: According to USP 2007 page # 1691. HPLC ASSAY OF CEPHALEXIN BASED ON HPLC ASSAY AM1172 (1.01) FOR CEPHALEXIN CAPSULES.500 MG / CAPSULES. I.PRINCIPLE: The sample is dissolved in water and the insoluble component removed by filtration. An aliquot of the filtrate is diluted with water and examined by reverse phase HPLC. II.APPARATUS 1. A suitable high performance liquid chromatographic system equipped with a variable Wavelength UV Detector. 2. A suitable analytical balance with tolerance of +/- 0.1 mg. 3. A suitable Ultrasonic bath. 4. Suitable Syringes such as BDà ¯Ã†â€™Ã‚ ¤, 10ml. 5. Analytical Column: 150 Ãâ€" 4.6 mm. i.d stainless steel column packed with S5 – ODS2 or equivalent column. 6. Pre-Column: 50 Ãâ€" 4.6 mm .i.d stainless steel column packed with 80 µm Porasil or equivalent is fitted between the pump and injector. 7 Detector Condition: 254nm range 0.5 aufs 8. Pump Condition: Flow rate 1.0 ml / minute. 9. Injection volume: 20 µl 10. pH meter. 11. Mobile phase: See reagents. B) REAGENTS Cephalexin analytical reference standard Methanol HPLC grade Acetonitrile HPLC grade 1- Hydroxybenzotriazole, Reagent grade. Triethylamine ( T.E.A ) analytical grade Orthophosphoric acid, analytical grade 1- Pentanesulfonic acid, sodium salt, Reagent grade (8) Mobile Phase: Dissolve 1g Pentanesulfonic acid sodium salt (Monohydrate) and 15ml of Triethylamine in 850 ml of distilled water, adjust the pH to 3.0 with Orthophosphoric acid. Add 50 ml of Methanol and 100 ml of Acetonitrile, Mix well and degas before use. Note: Caution should be taken when degassing the mobile phase to avoid evaporating the mixture. Internal standard solution: Dissolve 1 gm of 1- Hydroxybenzotriazole in 1000ml of mobile phase, mix well. C) PROCEDURE: This procedure contains the minimum recommended sample and standard Preparation for assays performed manually. Alternate weights and volumes may be substituted if necessary, as long as they are documented and provide nominally equivalent concentration of the analyte. PREPARATION OF REF. STANDARD SOLUTION Accurately weigh approximately 32, 40 and 48 mg of Cephalexin reference Standard in to into three separate 200ml volumetric flasks respectively, pipette 30 ml of the internal standard solution in to each flask and swirl to dissolve, Dilute to volume with distilled water and mix well. SAMPLE PREPARATION Take 20 random capsules from composite sample and note individual weight content of each capsule and determine average content weight of 20 capsules. Accurately weigh about 500 mg sample from composite sample of weight content of 20 capsules in 500ml volumetric flask and record the weight, add water to dissolve and make up the volume with water up to 500 ml mix well and filter. Take 20ml of above dilution in 100ml volumetric flask, add 30ml Internal Standard and then add water upto 100ml mix well and filter through 0.45 µm filter paper. d) CHROMATOGRAPHY Make 20 à ¯Ã‚ Ã‚ ­l injection of a standard to ensure the chromatography system complies with the system suitability criteria. The peak tailing should not be greater than 1.5, peak efficiency should be greater than 4000 plates. The resolution between the two peaks should be greater than 2.5. A typical chromatogram is attached. LIMIT OF CEPHALEXIN MONOHYDRATE CONTENT. CEPHALEXIN THEORY LABEL 500MG / CAPSULE 500MG / CAPSULE (As Cephalexin anhydrous) ( As Cephalexin anhydrous) Acceptance Limit: 475 – 525mg per capsule (95 – 105 %). Regulatory Limit: 462.5 – 550 mg per capsule (92.5 – 110 %) (British Pharmacopeia) REFERENCES: (Augsburger LL,Shangraw RF,Giannini RP, Shah VP, Prasad VK and Brown D (1983) Thiazides VIII: Dissolution Survey of marketed Hydrochlorothiazides tablets. J.Pharma Sci.,72(8):876-881) Anne H. Dantzig, Linda B. Tabas, Linda Bergin , Cefaclor uptake by the proton-dependent dipeptide transport carrier of human intestinal Caco-2 cells and comparison to cephalexin uptake Biochimica et Biophysica Acta (BBA) Biomembranes, Volume 1112, Issue 2, 9 December 1992, Pages 167-173. Chalermporn Thongpoon, Boonsom Liawruangrath, Saisunee Liawruangrath, R. Alan Wheatley, Alan Townshend , Flow injection chemiluminescence determination of cephalosporins in pharmaceutical preparations using tris (2,2†²-bipyridyl) ruthenium (II)-potassium permanganate system , Analytica Chimica Acta, Volume 553, Issues 1-2, 30 November 2005, Pages 123-133. (Farar WE (1985) Antibiotic resistance in developing countries. The Journal of Infectious Diseases,152(6):1103-1106 ) (Glass RI, Huq I, Alim ARM and yunus M (1980) Emergence of multiply antibiotic-resistant vibro cholerae in Bangladesh . The Journal of Infection Disease , 142(6):939-942 ) (Goodman Gilman`s-The Pharmacological Basis of Therapeutics (2006) 11th Edition, McGraw –Hill Medical Publishing Division, Digital Edition , Chapter1.) Godfried Owusu-Ababio, James A. Rogers, Hosmin Anwar , Method of evaluation of sustained release microsphere formulations using the open chemostat system. (Goodman Gilman`s-The Pharmacological Basis of Therapeutics (2006) 11th Edition) (Hassan SMR, Hossain MM,Akhter R,Karim SMH, Haque S,Kamaluddin M and Ghani A (2009) Pattern of antibiotic use at the primary health care level of Bangladesh : Survey report -1.S.J. Pharm. Sci.2 (1) : 1-7) Helio S. Sader, Michael R. Jacobs, Thomas R. Fritsche, Review of the spectrum and potency of orally administered cephalosporins and amoxicillin/clavulanate, Diagnostic Microbiology and Infectious Disease, Volume 57, Issue 3, Supplement 1, March 2007, Pages S5-S12. (Lina TT,Rahman SR, Gomes DJ(2007) Multi-antibiotic resistance mediated by plasmids and integrons in uropathogenic Escherichia coli and Klebsiella pneumoniea . Bangladesh Journal of Microbiology,24 (1):19-23) Lennart Venemalm , Pyrazinone conjugates as potential cephalosporin allergens Bioorganic Medicinal Chemistry Letters, Volume 11, Issue 14, 23 July 2001, Pages, 1869-1870. Luis J. Nuà ±ez-Vergara, J. A. Squella, M. M. Silva, Polarography of an acidic degradation product from cephalexin, Polarography of an acidic degradation product from cephalexin, Talanta, Volume 29, Issue 2, February 1982, Pages 137-138s. (Public Sector Drug use studies (1990-1993) International Network for Rational use of Drugs, Virginia,USA. ) Ralph R. Pfeiffer, K. S. Yang, Mary Ann Tucker, Crystal pseudopolymorphism of cephaloglycin and cephalexin, 19 June 1970, 10.1002/jps.2600591222 R.C.Rudoy,M.D. 1977, Cephalexin: Clinical and Laboratory Evaluation in Infants and Children , Clinical Pediatrics, Vol. 16, No. 7, 639-644 (1977) Rist T, Parish LC, Capin LR, Sulica V, Bushnell WD, Cupo MA, A comparison of the efficacy and safety of mupirocin cream and cephalexin in the treatment of secondarily infected eczema., 2002-01, Clin Exp Dermatol., 27(1):14-20 R.Wise, J. M. Andrews, J. P. Ashby, D. Thornber, Ceftibuten: A new orally absorbed cephalosporin in vitro activity against atrains from the United Kingdom ,Diagnostic Microbiology and Infectious Disease, Volume 14, Issue 1, January-February 1991, Pages 45-52. (Saha SK Baqui AH, Darmstadt GL, Ruhulamin M, Hanif M,Arifeen SE, Santosham M,Oishi K, Nagatake T and Black RE (2003) Composition of carriage and invasive pneumococci among Bangladesh children:implication for treatment policy and vaccine formulation. Journal of Clinical Microbiology,41 (12):5582-5587) Warren E. Wick, Cephalexin, a New Orally Absorbed Cephalosporin Antibiotic , Appl Environ Microbiol. 1967 July; 15(4): 765-769). Yagnesh P. Patel, Nehal Shah, Indravadan C. Bhoir, M. Sundaresan, Simultaneous determination of five antibiotics by ion-pair high-performance liquid chromatography Journal of Chromatography A, Volume 828, Issues 1-2, 18 December 1998, Pages 287-290. 1 | Page

Humanitys Fate in King Lear :: English Literature Essays

Humanity's Fate in King Lear Many tragedies have been written throughout history. The purpose of these tragedies were to illustrate some type of moral lesson. The tragic situation involves man's miscalculation of reality and the fatal results of those miscalculations. Our tragic hero must endure a great deal of suffering. It ends in his ruin or destruction. We must also understand that tragedy not only destroys the guilty, but also the innocent. The tragic hero represents what could happen to humankind. He is responsible for his society. He is a representation of our own fate. The fate of humanity will be discussed in King Lear, by William Shakespeare. In this moving play, our tragic hero was King Lear. Our tragic hero must also have a tragic flaw. Lear's tragic flaw was his vanity. Lear is so full of himself that he doesn't realize the truth. First of all, Lear wants to divide his kingdom up into three parts for his three daughters. Each daughter's portion depended on how much they would proclaim their love for him. Lear says, "Give me the map there. Know that we have divided in three our kingdom, and 'tis our fast intent to shake all cares and business from our age, conferring them on younger strengths while we unburdened crawl to death."(Act I, i, l. 38-41) Lear should not have relinquished his powers in the first place. He expects to be treated like a king when he no longer will have the power of a king. Secondly, he says, " Great rivals in our youngest daughter's love, long in our court have made their amorous sojourn, and here are to be answered. Tell me, my daughters ( Since now we will divest us both of rule, Interest of te rritory, cares of state), which of you should we say doth love us most? That we our largest bounty may extend where nature doth with merit challenge."(Act I, i, l. 47-53) Within these few lines, we see Lear's first sign of vanity. For one daughter to receive more land than another, one must proclaim their love to be more than the other. He is measuring their love with land. Naturally, his first two daughters, Goneril and Regan, will lie to him, but his vanity blinds him from the truth. Lear's first miscalculation was dividing his land between the daughters. The second is allowing his vanity to get the best of him.

Health Information Management System Proposal Essay

Health information technology can be best described as the point where information science, medicine, and healthcare all meet. The foundation of healthcare delivery consists of three major elements: cost, access, and quality. The U.S. government reportedly â€Å"hopes most Americans have electronic health records by 2014† (Ramachandran, 2013) .It is my proposal to upgrade to a current, cutting-edge health information management system in our office. Potential Benefits to the Practice Private practices are not a thing of the past. According to the AMA’s recent survey,†53.2% of physicians were self-employed in 2012, 41.8% were employed and 5% were independent contractors† (Robeznieks, 2013). Keeping that in mind, I have listed a few of the potential benefits of HIT to our practice: †¢Increased access to care – Having patient records stored electronically is in many cases, distance becomes irrelevant when consulting with a physician or the practice. For the patients that are out of the country or simply in another town, we can access their medical records and help them over the phone or allow other physicians access to their records at the patient’s request. †¢Allows for faster diagnosis when knowing the patient’s medical history and prescription history. Could possibly mean the difference between life and death. †¢Allows for a patient to record health information they measure at home, i.e. blood pressure, pulse, weight, blood glucose levels. This updated information can be used by the practice to keep tabs on patients for future visits or the need to schedule a visit. Potential Benefits to Staff In an online article written by Ken Terry, he stated that â€Å"41% of those who don’t have online access to records would consider switching physicians to obtain it† (Terry, 2013). Therefore, we need to look at other aspects that will benefit our staff in the long run. †¢Time equals money. Staff will spend less time retrieving, finding and filing patient charts. Now they can enter a patient’s name into the system and all their information will populate the screen. †¢Less money will be spent through the elimination of a transcription service as well as the transferring and transporting of patient charts. †¢Automated billing and accounting Necessary Training As one consulting company I spoke with stated, â€Å"understanding that one of the most important factors in a successful implementation is the quality of user training that takes place prior to the system activation† (Coastal Healthcare Consulting Inc., 2013). Due to the fact that we are a small practice, it will benefit everyone who has any contact with patients will be included in the training. Challenges with Implementing a New System †¢Over reliance on the accuracy of EMRs may lead to significant errors if a patient record contains false information. †¢Privacy and security risks due to hackers can include: identity theft, unauthorized access and corruption of patient data. †¢The cost of the equipment as well as the training that needs to be done. According to the Congressional Budget Office report written back in 2008 stated, â€Å"No aspect of health IT entails as much uncertainty as the magnitude of its potential benefits† (Devon M. Herrick, 2010). Our world has been radically changed in the last 5-10 years due to digital technology. Smart phones, tablets and web-enabled devices have changed the face of health care as we know it. This is our time to get involved and bring our practice into the present and solidify our future. References Coastal Healthcare Consulting Inc. (2013). Training. Retrieved September 22, 2013, from Coastal Healthcare Consulting Inc.: http://www.coastalhealthcare.com/services/training/ Devon M. Herrick, L. G. (2010). Health Information Technology: Benefits and Problems. Dallas: NCPA. Ramachandran, V. (2013, August 15). Technology Changing Healthcare. Retrieved September 20, 2013, from Mashable: http://mashable.com/2013/08/15/healthcare-and-it-health-informatics-infographic/ Robeznieks, A. (2013, September 17). Not All Doctors Giving Up Private Practice. Retrieved September 20, 2013, from Modern Health Care.com: http://www.modernhealthcare.com/article/20130917/BLOG/309179996 Terry, K. (2013, September 17). Patients Seek More Online Access To Medical Records. Retrieved September 19, 2013, from Information Week: http://www.informationweek.com/healthcare/policy/patients-seek-more-online-ac

Quotes From the Famous Novel Catch-22

Catch-22  by Joseph Heller is a famous anti-war novel. Even if youve never read the book, youve likely heard about its premise. The title of the book refers to a situation where no matter what choice you make the outcome will be bad. The concept has been widely referred to in popular culture.   Here are a few quotes from the novel to refresh your memory, to give you a taste for this classic, or just for you to enjoy the language and lines of Joseph Hellers famous work. Catch-22 Quotes Chapter 2 An unreasonable belief that everybody around him was crazy, a homicidal impulse to machine-gun strangers, retrospective falsification, an unfounded suspicion that people hated him and were conspiring to kill him. Chapter 3 He had decided to live forever or die in the attempt, and his only mission each time he went up was to come down alive. Chapter 4 Youre inches away from death every time you go on a mission. How much older can you be at your age. Chapter 5 Fortunately, just when things were blackest, the war broke out. There was only one catch and that was Catch-22, which specified that a concern for ones own safety in the face of dangers that were real and immediate was the process of a rational mind. Orr was crazy and could be grounded. All he had to do was ask; and as soon as he did, he would no longer be crazy and would have to fly more missions. Or would be crazy to fly more missions and sane if he didnt, but if he was sane he had to fly them. If he flew them he was crazy and didnt have to, but if he didnt want to he was sane and had to. Yossarian was moved very deeply by the absolute simplicity of this clause of Catch-22 and let out a respectful whistle. Thats some catch, that catch-22,  he observed. Its the best there is,  Doc Daneeka agreed. Chapter 6 Catch-22...says youve always got to do what your commanding officer tells you to. But Twenty-seventh Air Force says I can go home with forty missions. But they dont say you have to go home. And regulations do say you have to obey every order. Thats the catch. Even if the colonel were disobeying a Twenty-seventh Air Force order by making you fly more missions, youd still have to fly them, or youd be guilty of disobeying an order of his. And then the Twenty-seventh Air Force Headquarters would really jump on you.   Chapter 8   History did not demand Yossarians premature demise, justice could be satisfied without it, progress did not hinge upon it, victory did not depend on it. That men would die was a matter of necessity; which men would die, though, was a matter of circumstance, and Yossarian was willing to be the victim of anything but circumstance. But that was war. Just about all he could find in its favor was that it paid well and liberated children from the pernicious influence of their parents. Clevinger was a troublemaker and a wise guy. Lieutenant Scheisskopf knew that Clevinger might cause even more trouble if he wasnt watched. Yesterday it was the cadet officers; tomorrow it might be the world. Clevinger had a mind, and Lieutenant Scheisskopf had noticed that people with minds tended to get pretty smart at times. Such men were dangerous, and even the new cadet officers whom Clevinger had helped into office were eager to give damning testimony against him. The case against Clevinger was open and shut. The only thing missing was something to charge him with. Ill tell you what justice is. Justice is a knee in the gut from the floor on the chin at night sneaky with a knife brought up down on the magazine of a battleship sandbagged underhanded in the dark without a word of warning.   Chapter 9 Some men are born mediocre, some men achieve mediocrity, and some men have mediocrity thrust upon them.    With a little ingenuity and vision, he had made it all but impossible for anyone in the squadron to talk to him, which was just fine with everyone, he noticed, since no one wanted to talk to him anyway.   Chapter 10 Major Major never sees anyone in his office while hes in his office. Chapter 12 Open your eyes, Clevinger. It doesnt make a damned bit of difference who wins the war to someone whos dead. The enemy, retorted Yossarian with weighted precision, is anybody whos going to get you killed, no matter which side hes on, and that includes Colonel Cathcart. And dont you forget that, because the longer you remember it, the longer you might live.   Yossarian sidled up drunkenly to Colonel Korn at the officers club one night to kid with him about the new Lepage gun that the Germans had moved in. What Lepage gun? Colonel Korn inquired with curiosity. The new three hundred and forty four millimeter Lepage glue gun, Yossarian answered. It glues a whole formation of planes together in mid-air. Yossarians heart sank. Something was terribly wrong if everything was all right and they had no excuse for turning back. Chapter 13 You know, that might be the answer - to act boastfully about something we ought to be ashamed of. Thats a trick that never seems to fail.   Chapter 17 There was a much lower death rate inside the hospital than outside the hospital and a much healthier death rate. Few people died unnecessarily. People knew a lot more about dying inside the hospital and made a much neater, more orderly job of it. They couldnt dominate Death inside the hospital, but they certainly made her behave. They had taught her manners. They couldnt keep death out, but while she was in she had to act like a lady. People gave up the ghost with delicacy and taste inside the hospital. There was none of that crude, ugly ostentation about dying that was so common outside the hospital. They did not blow up in mid-air like Kraft or the dead man in Yossarians tent or freeze to death in the blazing summertime the way Snowden had frozen to death after spilling his secret to Yossarian in the back of the plane. Chapter 18 Dont tell me God works in mysterious ways, Yossarian continued, hurtling on over her objection. Theres nothing so mysterious about it. Hes not working at all. Hes playing. Or else Hes forgotten all about us. Thats the kind of God you people talk about - a country bumpkin, a clumsy, bungling, brainless, conceited, uncouth hayseed. Good God, how much reverence can you have for a Supreme Being who finds it necessary to include such phenomena as phlegm and tooth decay in His divine system of creation? What in the world was running through that warped, evil, scatological mind of His when He robbed old people of the power to control their bowel movements? Why in the world did He ever create pain?   Pain? Lieutenant Scheisskopfs wife pounced upon the word victoriously. Pain is a useful symptom. Pain is a warning to us of bodily dangers.   Chapter 20 He had failed miserably, had choked up once again in the face of opposition from a stronger personality. It was a familiar, ignominious experience, and his opinion of himself was low. Chapter 36 And looking very superior, he tossed down on the table a photostatic copy of a piece of V mail in which everything but the salutation Dear Mary had been blocked out and on which the censoring officer had written, I long for you tragically. R. O. Shipman, Chaplain, U.S. Army. Chapter 39 Morale was deteriorating and it was all Yossarians fault. The country was in peril; he was jeopardizing his traditional rights of freedom and independence by daring to exercise them. Chapter 42 Run away to Sweden, Yossarian. And Ill stay here and persevere. Yes. Ill persevere. Ill nag and badger Colonel Cathcart and Colonel Korn every time I see them. Im not afraid.