Ampicillin CAS 7177-48-2
Introduction：Basic information about Ampicillin CAS 7177-48-2, including its chemical name, molecular formula, synonyms, physicochemical properties, and safety information, etc.
Ampicillin Basic informationDescription References
| Product Name: | Ampicillin |
| Synonyms: | amcap;amcill;aminobenzylpenicillintrihydrate;amperil;ampichel;ampinova;ro-ampen;trafarbiot |
| CAS: | 7177-48-2 |
| MF: | C16H25N3O7S |
| MW: | 403.45 |
| EINECS: | 615-347-9 |
| Product Categories: | Antibiotics for Research and Experimental Use;beta-Lactams (Antibiotics for Research and Experimental Use);Biochemistry;Pharma;7177-48-2 |
| Mol File: | 7177-48-2.mol |
Ampicillin Chemical Properties
| Melting point | 208 °C (dec.)(lit.) |
| Boiling point | 684℃ |
| refractive index | 265 ° (C=0.1, H2O) |
| Fp | 87 °C |
| storage temp. | Sealed in dry,2-8°C |
| solubility | NH4OH 1 M: 50 mg/mL, clear, colorless |
| form | solid |
| color | white to off-white |
| pka | 2.5 (COOH)(at 25℃) |
| Water Solubility | 0.1-1 g/100 mL at 21 ºC |
| Merck | 14,586 |
| BRN | 5399534 |
| Stability: | Hygroscopic |
| Major Application | pharmaceutical (small molecule) |
| InChIKey | RXDALBZNGVATNY-CWLIKTDRSA-N |
| SMILES | O.O.O.CC1(C)S[C@@H]2[C@H](NC(=O)[C@H](N)c3ccccc3)C(=O)N2[C@H]1C(O)=O |
| CAS DataBase Reference | 7177-48-2(CAS DataBase Reference) |
| EPA Substance Registry System | Ampicillin trihydrate (7177-48-2) |
Safety Information
| Hazard Codes | Xn,Xi |
| Risk Statements | 36/37/38-42/43 |
| Safety Statements | 22-26-36/37-36-45-23 |
| WGK Germany | 2 |
| RTECS | XH8425000 |
| F | 3-10 |
| HS Code | 29411020 |
| Storage Class | 11 - Combustible Solids |
| Hazard Classifications | Eye Irrit. 2 Resp. Sens. 1 Skin Irrit. 2 Skin Sens. 1 STOT SE 3 |
| Toxicity | LD50 orl-rat: 10 g/kg ANTBAL 20,653,75 |
| Description | As a penicillin group of beta-lactam antibiotics, Ampicillin is the first broad-spectrum penicillin, which has in vitro activity against Gram-positive and Gram-negative aerobic and anaerobic bacteria, commonly used for preventing and treating bacterial infections of respiratory tract, urinary tract, middle ear, sinuses, stomach and intestines, bladder, and kidney, etc. caused by susceptible bacteria. It is also used to treat uncomplicated gonorrhea, meningitis, endocarditis salmonellosis, and other serious infections through administered by mouth, intramuscular injection or by intravenous infusion. Like all antibiotics, it is not effective for the treatment of viral infections. Ampicillin functions by killing the bacteria or preventing their growth. After penetrating Gram-positive and Gram-negative bacteria, it acts as an irreversible inhibitor of the enzyme transpeptidase needed by bacteria to make the cell wall, which results to the inhibition of cell wall synthesis and eventually leads to cell lysis. |
| References | https://en.wikipedia.org/wiki/Ampicillin https://www.drugbank.ca/drugs/DB00415 http://www.medicinenet.com/ampicillin/article.htm |
| Chemical Properties | White or almost white, crystalline powder. |
| Chemical Properties | Ampicillin in anhydrous form occurs ascrystals. |
| Originator | Polycillin,Bristol,US,1963 |
| Uses | Commonly used to select for ampicillin resistance in mutated and transformed cells |
| Uses | Penicillin antibacterial. |
| Indications | Ampicillin may also be helpful in certain patients, particularly pregnantwomen with acne, for whom the use of tetracycline, erythromycin, andminocycline should be avoided. In resistant acne patients, culture may reveala gram-negative bacteria responsive to ampicillin. |
| Definition | ChEBI: Ampicillin trihydrate is a hydrate. It contains an ampicillin. |
| Manufacturing Process | The known methods for the preparation of D-(-)-α-aminobenzylpenicillin bythe acylation of 6-aminopenicillanic acid result in the preparation of aqueousmixtures which contain, in addition to the desired penicillin, unreacted 6-aminopenicillanic acid, hydrolyzed acylating agent, and products of sidereactions such as the products of the acylating agent reacted with itselfand/or with the desired penicillin, as well as other impurities. The D-(-)-α-aminobenzylpenicitlin may then be recovered from the aqueousreaction mixture by concentration to small volume and recovering the productby filtration. However, due to the fact that anhydrous D-(-)-α-aminobenzylpenicillinis soluble in water to the extent of about 20-25 mg/ml at20°-25°C, it is very difficult to recover the product in high yields.Furthermore, the recovered D-(-)-α-aminobenzylpenicillin may be obtained inthe form of a monohydrate. The monohydrates (as well as the dihydrates) ofD-(-)-α-aminobenzylpenicillin possess poor biological stability. The trihydrate which is obtained in high yields, is relatively insoluble in water,possesses high biological stability and can be obtained by contacting, at atemperature not above 60°C, an acid addition salt of D-(-)-α-aminobenzylpenicillin with an amine in a water immiscible solvent containingat least 3 mols of water per mol of such penicillin. The following is an example of the conduct of such a process. To a vigorouslyagitated mixture of 100 ml of methyl isobutyl ketone there are added at 25°to 30°C 15 ml of water and 10 ml of a mixture of secondary amines. To this mixture there is then added slowly over a period of 30 minutes 10grams of D-(-)-α-aminobenzylpenicillin α-naphthalenesulfonate. The mixture isagitated for 3 hours at 25-30°C. The product, D-(-)-α-aminobenzylpenicillintrihydrate precipitates and is collected by filtration. The filter cake of theproduct is washed several times with methyl isobutyl ketone and is dried at40°C. The product is obtained in about a 90% yield and has a potency of 865mcg/mg. It is determined by Karl Fischer analysis to have a moisture contentof 13.4% by weight. |
| Brand name | Amcill (Parke-Davis); Omnipen (Wyeth-Ayerst);Polycillin (Apothecon); Principen (Apothecon). |
| Therapeutic Function | Antibacterial |
| Antimicrobial activity | Ampicillin is slightly less active than benzylpenicillinagainst most Gram-positive bacteria but is moreactive against E. faecalis. MRSA and strains of Str. pneumoniaewith reduced susceptibility to benzylpenicillin are resistant.Most group D streptococci, anaerobic Gram-positive cocciand bacilli, including L. monocytogenes, Actinomyces spp. andArachnia spp., are susceptible. Mycobacteria and nocardia areresistant. Ampicillin has similar activity to benzylpenicillin againstN. gonorrhoeae, N. meningitidis and Mor. catarrhalis. It is 2–8times more active than benzylpenicillin against H. influenzaeand many Enterobacteriaceae, but β-lactamase-producingstrains are resistant. Pseudomonas spp. are resistant, butBordetella, Brucella, Legionella and Campylobacter spp. areoften susceptible. Certain Gram-negative anaerobes suchas Prevotella melaninogenica and Fusobacterium spp. are susceptible,but B. fragilis is resistant, as are mycoplasmas andrickettsiae. Activity against molecular class A β-lactamase-producingstrains of staphylococci, gonococci, H. influenzae, Mor. catarrhalis,certain Enterobacteriaceae and B. fragilis is enhanced bythe presence of β-lactamase inhibitors, specifically clavulanicacid. Its bactericidal activity resembles that of benzylpenicillin.Bactericidal synergy occurs with aminoglycosides againstE. faecalis and many enterobacteria, and with mecillinamagainst a number of ampicillin-resistant enterobacteria. |
| Acquired resistance | β-Lactamase-producing pathogens, including most clinicalisolates of Staph. aureus, are resistant. Strains of pneumococci,enterococci, gonococci and H. influenzae with alteredPBPs have reduced susceptibility to ampicillin. Isolatesof N. gonorrhoeae and H. influenzae with a TEM plasmid-mediatedβ-lactamase (which are more common) are fullyresistant. Resistance among H. influenzae is often linked withresistance to chloramphenicol, erythromycin or tetracycline,due to plasmid-encoded resistance markers that are co-transferredwith the gene for the TEM enzyme. However, atleast 70% of current H. influenzae isolates remain susceptibleto ampicillin worldwide. The widespread use of ampicillin and other aminopenicillinshas led to resistance becoming common in formerlysusceptible species of enteric pathogens as a result of thewidespread dissemination of plasmid-mediated β-lactamases.Surveillance data from North America and Europe indicateless than 50% susceptibility to ampicillin in Esch. coli. At least90% of current isolates of Mor. catarrhalis are β-lactamaseproducingstrains. Ampicillin-resistant strains of salmonellae,notably S. enterica serotypes Typhi and Typhimurium (many of which are also resistant to chloramphenicol, sulfonamidesand tetracyclines) present a serious problem in Africa, Asiaand South America. Multiresistant strains of shigellae alsopredominate in many parts of the world. |
| General Description | Odorless white microcrystalline powder with a bitter taste. A 0.25% solution in water has a pH of 3.5 to 5.5. |
| Air & Water Reactions | Slightly soluble in water. |
| Reactivity Profile | Ampicillin absorbs insignificant amounts of moisture at 77° F and relative humidities up to approximately 80%, but under damper conditions Ampicillin absorbs significant amounts. A pH-rate profile reveals specific-acid- and specific-base- catalyzed hydrolysis. The pH of maximum stability is 5.8. |
| Fire Hazard | Flash point data for Ampicillin are not available; however, Ampicillin is probably combustible. |
| Contact allergens | Ampicillin caused contact dermatitis in a nurse alsosensitized to amoxicillin (with tolerance to oral phenoxymethylpenicillin)and in a pharmaceutical factoryworker. Systemic drug reactions are common. Crossreactivityis regular with ampicillin and can occur withother penicillins. |
| Biochem/physiol Actions | A β-lactam antibiotic with an amino group side chain attached to the penicillin structure. Penicillin derivative that inhibits bacterial cell-wall synthesis (peptidoglycan cross-linking) by inactivating transpeptidases on the inner surface of the bacterial cell membrane. Bactericidal only to growing Escherichia coli . Mode of resistance: Cleavage of β-lactam ring of ampicillin by β-lactamase. Antimicrobial spectrum: Gram-negative and Gram-positive bacteria. |
| Pharmacokinetics | Oral absorption: 30–40% Cmax 500 mg oral: 3.2 mg/L after c. 2 h 500 mg intramuscular: 5–15 mg/L after 1 h 500 mg intravenous infusion: 12–29 mg/L Plasma half-life: 1–1.5 h Volume of distribution: 0.38 L/kg Plasma protein binding: 20% Absorption and distribution Ampicillin is highly stable to acid: in 2 h at pH 2 and 37°C, only 5% of activity is lost. Absorption is impaired when it is given with meals. It is distributed in the extracellular fluid. Adequate concentrations are obtained in serous effusions. Effective CSF levels are obtained only in the presence of inflammation, variable peak concentrations around 3 mg/L being found in the first 3 days of treatment in patients receiving 150 mg/kg per day. It accumulates and persists in the amniotic fluid. Metabolism and excretion A small proportion is converted to penicilloic acid. About 34% of an oral dose and 60–80% of parenteral doses are recoverable from the urine, where concentrations around 250–1000 mg/L appear. Excretion is partly in the glomerular filtrate and partly by tubular secretion, which can be blocked by probenecid. Impairment of renal function reduces the rate of excretion, the plasma half-life rising to 8–9 h in anuric patients. Although excretion is mainly renal, up to 50 times the corresponding serum level may be attained in the bile. There is a degree of enterohepatic recirculation and significant quantities appear in the feces. Bioavailability may be affected in severe liver disease. |
| Clinical Use | Ampicillin, 6-[D-α-aminophenylacetamido]penicillanic acid,D-α-aminobenzylpenicillin (Penbritn, Polycillin, Omnipen,Amcill, Principen), meets another goal of the research onsemisynthetic penicillins—an antibacterial spectrum broaderthan that of penicillin G. This product is active against thesame Gram-positive organisms that are susceptible to otherpenicillins, and it is more active against some Gram-negativebacteria and enterococci than are other penicillins.Obviously, the α-amino group plays an important role in thebroader activity, but the mechanism for its action isunknown. It has been suggested that the amino group confersan ability to cross cell wall barriers that are impenetrableto other penicillins. D-(－)-Ampicillin, prepared from D-(－)-α-aminophenylacetic acid, is significantly more active thanL-(＋)-ampicillin. Ampicillin is water soluble and stable in acid. Theprotonated α-amino group of ampicillin has a pKa of 7.3,46and thus it is protonated extensively in acidic media, whichexplains ampicillin’s stability to acid hydrolysis and instabilityto alkaline hydrolysis. It is administered orally andis absorbed from the intestinal tract to produce peak plasmaconcentrations in about 2 hours. Oral doses must be repeatedabout every 6 hours because it is excreted rapidly andunchanged through the kidneys. It is available as a white, crystalline, anhydrous powder that is sparingly soluble inwater or as the colorless or slightly buff-colored crystallinetrihydrate that is soluble in water. Either form may be usedfor oral administration, in capsules or as a suspension.Earlier claims of higher plasma levels for the anhydrousform than for the trihydrate following oral administrationhave been disputed. The white, crystalline sodium salt isvery soluble in water, and solutions for injections should beadministered within 1 hour after being made. |
| Clinical Use | Isolates should be tested for susceptibility before use, especiallyfor serious infections. For oral therapy, amoxicillin ispreferable to ampicillin. Urinary tract infections Bacterial meningitis Respiratory tract infections Gastrointestinal infections, including typhoid fever and bacillary dysenteryEnterococcal endocarditis and septicemia (in combination with anaminoglycoside) Listeriosis (in combination with an aminoglycoside) |
| Side effects | Ampicillin is generally free from severe toxicity and, apartfrom gastrointestinal intolerance, the only significant sideeffects seen have been rashes. In common with other semisyntheticpenicillins, it appears to be less likely than benzylpenicillinto elicit true allergic reactions. However, it is morelikely to cause rashes, which are found in approximately 9% oftreated patients and which occur more frequently in patientsreceiving large doses or in renal failure. Rashes occur in 95% of patients with infectious mononucleosis or other lymphoiddisorders. This unusual susceptibility disappears when thedisease resolves. In keeping with a toxic rather than an allergicorigin, skin tests to ampicillin and to mixed-allergen moietiesof benzylpenicillin are negative. Since the typical maculopapularrash of ampicillin does not have an allergic origin, itsdevelopment does not indicate penicillin allergy and is not acontraindication to the use of other penicillins. Gastrointestinal side effects are relatively common (around10%) in patients treated with oral ampicillin, and occur in2–3% of patients given the drug parenterally, presumably asa result of drug entering the gut through the bile. The veryyoung and the old are most likely to suffer. Diarrhea can besufficiently severe to require withdrawal of treatment andpseudomembranous colitis may occur. Interference with thebowel flora, which is presumably implicated in diarrhea, canalso affect enterohepatic recirculation of steroids, and thederangement can be sufficient to impair the absorption of oralcontraceptives and affect the interpretation of estriol levels. |
| Safety Profile | Mildly toxic byingestion. An experimental teratogen. Otherexperimental reproductive effects. Whenheated to decomposition it emits toxicfumes of SO,xand NOx. |
| Synthesis | Ampicillin, [2S-[2α,5α,6β(S)]]-3,3-dimethyl-7-oxo-6-(2-amino-2-phenylacetamido)-4-thia-azabicylco[3.2.0]-heptan-2-carboxylic acid (32.1.1.16), is synthesized in various ways using different methods of protection of amino group in the starting phenylglycine. One of the most widely used methods uses the benzyl chloroformate. Reacting this with phenylglycine initially forms benzyloxycarbonylphenylglycine (32.1.1.13). Treating this with ethyl chloroformate in the presence of triethylamine gives a mixed anhydride (32.1.1.14) with a protected amino group that easily reacts with 6-APA in the presence of sodium bicarbonate, to form the sodium salt of the N-benzyloxycarbonyl-protected ampicillin (32.1.1.15). Removing the protecting group by hyrogenolysis using a palladium on barium carbonate catalyst gives the desired ampicillin (32.1.1.16). Another method of making ampicillin is analogous to the method described above, and it differs in the method of protecting the α-amino group in the initial phenylglycine. In order to do this, acetoacetic ester is reacted with the sodium salt of phenylglycine, which forms an intermediate—aminocrontonic ester (32.1.1.17). Subsequent transformation of this product to the mixed anhydride (32.1.1.18) followed by a reaction with 6-APA in the presence of sodium bicarbonate gives ampicillin (32.1.1.16) in the form of a sodium salt. A method of directly acylating 6-APA with phenylglycine chloride hydrochloride also has been proposed. |
| Potential Exposure | Used as an antibiotic. |
| Drug interactions | Potentially hazardous interactions with other drugs Ciclosporin: may increase ciclosporin levels. Reduces excretion of methotrexate (increased risk of toxicity). |
| Metabolism | Ampicillin is metabolised to some extent to penicilloic acid which is excreted in the urine. Renal clearance of ampicillin occurs partly by glomerular filtration and partly by tubular secretion; it is reduced by probenecid. About 20-40% of an oral dose and 60-80% of an IV dose may be excreted unchanged in the urine in 6 hours. High concentrations are reached in bile; it undergoes enterohepatic recycling and some is excreted in the faeces. |
| Shipping | UN3077 Environmentally hazardous substances,solid, n.o.s., Hazard class: 9; Labels: 9-Miscellaneous hazardousmaterial, Technical Name Required. |
| Incompatibilities | May be incompatible with oxidizers(chlorates, nitrates, peroxides, permanganates, perchlorates,chlorine, bromine, fluorine, etc.); contact may cause firesor explosions. Keep away from alkaline materials, strongbases, strong acids, oxoacids, epoxides. |
| Waste Disposal | It is inappropriate and possiblydangerous to the environment to dispose of expired or wastepharmaceuticals by flushing them down the toiletor discarding them to the trash. Household quantities ofexpired or waste pharmaceuticals may be mixed with wet catlitter or coffee grounds, double-bagged in plastic, discard intrash. Larger quantities shall carefully take into considerationapplicable DEA, EPA, and FDA regulations. If possible returnthe pharmaceutical to the manufacturer for proper disposalbeing careful to properly label and securely package the material.Alternatively, the waste pharmaceutical shall be labeled,securely packaged and transported by a state licensed medicalwaste contractor to dispose by burial in a licensed hazardousor toxic waste landfill or incinerator. |
Ampicillin Preparation Products And Raw materials
| Raw materials | Triethylamine-->Pivaloyl chloride-->SECONDARYAMINES-->Urea, N,N-bis(trimethylsilyl)--->6-Aminopenicillanic acid-->Chlorotrimethylsilane-->Dichloromethane |
| Preparation Products | 6-Aminopenicillanic acid |
