| Identification | More | [Name]
Ceftriaxone sodium | [CAS]
74578-69-1 | [Synonyms]
CEFATRIAXONE
CEFTRIAXONE
2,5,6-tetrahydro-2-methyl-5,6-dioxo-)(methoxyimino)acetyl)amino)-8-oxo-3-(((
4-triazin-3-yl)thio)methyl)-,sodiumsalt,hydrate(2:4:7)(6r-(6-alpha,7-2
beta(z)))-
cefatriaxonehydrate
cephtriaxone
ro13-9904
rocephin
x13-9904
5-Thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid, 7-[[(2-amino-4-thiazolyl)(methoxyimino)acetyl]amino]-8-oxo-3-[[(1,2,5,6-tetrahydro-2-methyl-5,6-dioxo-1,2,4-triazin-3-yl)thio]methyl]-, disodium salt, [6R-[6alpha,7beta(Z)]]-
CEFTRIAXONE SODIUM, USP
5-Thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid, 7-[[(2-amino-4-thiazolyl)(methoxyimino)acetyl]amino]-8-oxo-3-[[(1,2,5,6-tetrahydro-2-methyl-5,6-dioxo-1,2,4-triazin-3-yl)thio]methyl]-, disodium salt, [6R-[6α,7β(Z)]]-
5-Thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid, 7-[[(2Z)-(2-amino-4-thiazolyl)(methoxyimino)acetyl]amino]-8-oxo-3-[[(1,2,5,6-tetrahydro-2-methyl-5,6-dioxo-1,2,4-triazin-3-yl)thio]methyl]-, disodium salt, (6R,7R)-
Ceftriaxone disodium
Longaceph
Ceftriaxonesodiumnon-steriled
[6R-[6alpha,7beta(Z)]]-7-[[(2-Amino-4-thiazolyl)(methoxyimino)acetyl]amino]-8-oxo-3-[[(1,2,5,6-tetrahydro-2-methyl-5,6-dioxo-1,2,4-triazin-3-yl)thio]methyl]-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid sodium salt | [EINECS(EC#)]
277-930-0 | [Molecular Formula]
C18H18N8O7S3 | [MDL Number]
MFCD00865013 | [Molecular Weight]
554.58 | [MOL File]
74578-69-1.mol |
| Chemical Properties | Back Directory | [storage temp. ]
4°C, protect from light | [solubility ]
Soluble in DMSO (50 mM) | [form ]
Solid | [color ]
White to off-white | [Water Solubility ]
Water : ≥ 40 mg/mL (66.60 mM) | [InChIKey]
CDCJSJLFRBHEHN-ZZKDXJNYNA-N | [SMILES]
C(C1=C(CS[C@]2([H])[C@H](NC(=O)/C(/C3N=C(N)SC=3)=N\OC)C(=O)N12)CSC1=NC(=O)C(=O)NN1C)(=O)O.[NaH] |&1:5,7,r| | [CAS DataBase Reference]
74578-69-1(CAS DataBase Reference) |
| Hazard Information | Back Directory | [Hazard]
Moderately toxic. Low toxicity by inges-
tion. Human systemic effects.
| [Description]
Ceftriaxone is a cephalosporin (SEF a low spor in) antibiotic that is used to treat conditions such as lower respiratory tract infections, skin and skin structure infections, urinary tract infections, pelvic inflammatory disease, bacterial septicemia, bone and joint infections, and meningitis. | [Originator]
Rocephin,Roche,Switz.,1982 | [Uses]
Ceftriaxone sodium is antibacteria.
| [Manufacturing Process]
19 g of (6R,7R)-7-[2-[2-(2-chloroacetamido)-4-thiazolyl]-2-(methoxyimino)
acetamido]-8-oxo-3-[[(1,4,5,6-tetrahydro-4-methyl-5,6-dioxo-as-triazin-3-
yl)thio]methyl]-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid are
suspended in 150 ml of water together with 9.5 g of thiourea. The pH is
adjusted to 6.8 with 5% sodium hydrogen carbonate solution while gassing
with nitrogen and stirring, there being obtained a yellow-orange solution. The
pH of the solution is held constant at 6.8-7.0 for 6 hours by adding sodium
hydrogen carbonate solution by means of an autotitrator. 100% formic acid is
added to the orange colored solution until the pH is 3.5. The precipitated
material is filtered off under suction and washed with 100 ml of 10% formic
acid. This material is denoted as (1). The filtrate is adjusted to pH 2.5 by
adding 100% formic acid, whereby additional substance precipitates out. The
mixture is held in an ice-bath for 1 hour, the precipitated substance is then
filtered off and washed with a small amount of ice-water. This material is
denoted as fraction I. The aforementioned orange-brown material (1) is
suspended in 250 ml of water. The suspension is adjusted to pH 7 with 2 N
sodium hydroxide, there being obtained an orange-brown solution. Additional
100% formic acid is added to this solution until the pH is 3.5. The material which thereby precipitates out is filtered off under suction and discarded. The
filtrate is adjusted to pH 2.5 with 100% formic acid, whereby additional
substance precipitates out. The mixture is held in an ice-bath for 1 hour, the
precipitated substance is then filtered off under suction and washed with a
small amount of ice-water. This material is denoted as fraction II. Fractions I
and II are suspended together in 500 ml of ethanol and evaporated in a
rotary evaporator in order to remove water. After adding ether, the mixture is
filtered under suction and the precipitate is washed successively with ether
and low-boiling petroleum ether. There is thus obtained the title substance in
the form of a yellowish solid material which is denoted as A.
The mother liquors and washings of fractions I and II are concentrated from a
volume of about 1.7 liters to 250 ml, the pH is adjusted to 2.5 with 100%
formic acid and the solution is stored overnight in a refrigerator, whereby
further substance crystallizes. This is filtered off under suction and washed
with a small amount of water. The residue on the suction filter is
azeotropically distilled with ethanol. There is obtained solid, almost colorless
title substance which is denoted as B. B is purer than A according to thin-layer
chromatography.
In order to obtain pure title substance, the acid B is suspended in 150 ml of
methanol and treated while stirring with 10 ml of a 2 N solution of the sodium
salt of 2-ethylcaproic acid in ethyl acetate. After about 10 minutes, there
results a solution which is treated with 100 ml of ethanol. The mixture is
extensively concentrated at 40°C in vacuo. The sodium salt precipitates out in
amorphous form after adding ethanol. This salt is filtered off under suction,
washed successively with ethanol and low-boiling petroleum ether and dried at
40°C in a high vacuum. There is obtained the title substance in the form of an
almost colorless amorphous powder. | [Brand name]
Rocephin (Roche). | [Therapeutic Function]
Antibacterial | [General Description]
Ceftriaxone was synthesized by HoffmannLa Roche in 1981. The triazinyl moiety was introduced at the 3 position of the cephem nucleus. The same side chain as possessed by cefotaxime and the other so-called third-generation cephalosporins was retained at the 7 position. The antibacterial activity of ceftiaxone is almost the same as that of cefotaxime in vitro, but its in vivo activity is 10 to 100 times higher. Its most characteristic property is its seven to eight hour half-life in serum, the longest among the known cephem antibiotics. | [Mechanism of action]
Ceftriaxone is a bactericidal agent that acts by inhibition of bacterial cell wall synthesis. Ceftriaxone has activity in the presence of some beta-lac- tamases, both penicillinases and cephalosporinases, of Gram-negative and Gram-positive bacteria. Ceftriaxone works by inhibiting the mucopeptide synthesis in the bacterial cell wall. The β-lactam core of ceftriaxone binds to carboxypeptidases, endopeptidases, and transpeptidases in the bacterial cytoplasmic membrane. These enzymes are involved in cell wall synthesis and cell division. By binding to these enzymes, ceftriaxone causes formation of defective cell walls and promotes cell death[1].
| [Clinical Use]
Ceftriaxone sodium is a β-lactamase–resistantcephalosporin with an extremely long serum half-life.Once-daily dosing suffices for most indications. Two factorscontribute to the prolonged duration of action ofceftriaxone: high protein binding in the plasma and slowurinary excretion. Ceftriaxone is excreted in both the bileand the urine. Its urinary excretion is not affected byprobenecid. Despite its comparatively low volume ofdistribution, it reaches the cerebrospinal fluid in concentrationsthat are effective in meningitis. Nonlinear pharmacokineticsare observed.
Ceftriaxone contains a highly acidic heterocyclic systemon the 3-thiomethyl group. This unusual dioxotriazine ringsystem is believed to confer the unique pharmacokineticproperties of this agent. Ceftriaxone has been associatedwith sonographically detected “sludge,” or pseudolithiasis,in the gallbladder and common bile duct. Symptoms ofcholecystitis may occur in susceptible patients, especiallythose on prolonged or high-dose ceftriaxone therapy. Theculprit has been identified as the calcium chelate.
Ceftriaxone exhibits excellent broad-spectrum antibacterialactivity against both Gram-positive and Gram-negativeorganisms. It is highly resistant to most chromosomally andplasmid-mediated β-lactamases. The activity of ceftriaxoneagainst Enterobacter, Citrobacter, Serratia, indole-positiveProteus, and Pseudomonas spp. is particularly impressive. Itis also effective in the treatment of ampicillin-resistant gonorrheaand H. influenzae infections but generally less activethan cefotaxime against Gram-positive bacteria and B.fragilis.
| [Side effects]
Ceftriaxone sodium is a bactericidal agent that acts by inhibition of bacterial cell
wall synthesis. Ceftriaxone has activity in the presence of some beta-lactamases, both penicillinases and cephalosporinases, of Gram-negative and
Gram-positive bacteria. | [Side effects]
Common side effects of Ceftriaxone sodium include:
symptoms of a blood cell disorder;
diarrhea;
vaginal itching or discharge;
warmth, tight feeling, or a hard lump where the injection was given;
rash;
abnormal liver function tests. | [Synthesis]
A solution of sodium-2-ethyl hexanoate (390 g) in acetone (2.0 Ltr) is added to the wet Ceftriaxone acid obtained in Example 2 is suspended in a mixture of acetone and water. The reaction mixture is charcoalized and filtered. To the clear filtrate is added acetone whereupon the product precipitated. The precipitated solid is filtered, washed with acetone and dried to get 515 g of Ceftriaxone sodium hemiheptahydrate. HPLC purity = Above 99.5%. | [Veterinary Drugs and Treatments]
Ceftriaxone is used to treat serious infections, particularly against
susceptible Enterobacteriaceae that are not susceptible to other less
expensive agents or when aminoglycosides are not indicated (due
to their potential toxicity). Its long half life, good CNS penetration,
and activity
against Borrelia burgdorferi also has made it a potential
choice for treating Lyme’s disease. | [storage]
4°C, protect from light | [References]
[1] Rawls S, et al. Antibiotics, β-Lactam. Encyclopedia of the Neurological Sciences, 2014; 207-209. |
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