Transcript Slide 1

Класификация
• Според механизма на действие:
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Инхибиране на синтеза на клетъчната среда;
Инхибиране на белтъчния синтез;
Инхибиране на синтеза на нуклеиновите киселини;
Инхибиране на синтеза и функциите на цитоплазмената мембрана;
Недостатъчно изяснени механизми.
• Според химична структура:
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β-лактами - пеницилини и цефалоспорини;
Аминогликозиди;
Макролиди;
Aроматни;
Тетрациклини;
Полипептиди;
Производни на АК.
Тетрациклинови антибиотици
Природни
Tetracycline
Chlortetracycline
Oxytetracycline
Demeclocycline
Полусинтетични
Doxycycline
Lymecycline
Meclocycline
Methacycline
Minocycline
Rolitetracycline
DEFINITION
(4S,4aS,5aS,6S,12aS)-4-(Dimethylamino)-3,6,10,12,12a-pentahydroxy-6-methyl-1,11dioxo-1,4,4a,5,5a,6,11,12a-octahydrotetracene-2-carboxamide.
Content
88.0 per cent to 102.0 per cent (dried substance).
CHARACTERS
Yellow, crystalline powder.
Solubility
Very slightly soluble in water, soluble in ethanol (96 per cent) and in methanol, sparingly
soluble in acetone. It dissolves in dilute acid and alkaline solutions.
H3C
H3C
CH3
N
N
H
CH3
H
OH
OH
4
4
NH2
NH2
O
O
O
O
Related substances
epi
natural
Liquid chromatography (2.2.29).
Prepare the solutions immediately before use.
Test solution Dissolve 25.0 mg of the substance to be examined in 0.01 M hydrochloric acid and
dilute to 25.0 ml with the same acid.
Reference solution (a) Dissolve 25.0 mg of tetracycline hydrochloride CRS in 0.01 M hydrochloric
acid and dilute to 25.0 ml with the same acid.
Reference solution (b) Dissolve 12.5 mg of 4-epitetracycline hydrochloride CRS in
hydrochloric acid and dilute to 50.0 ml with the same acid.
Reference solution (c) Dissolve 10.0 mg of anhydrotetracycline hydrochloride CRS
hydrochloric acid and dilute to 100.0 ml with the same acid.
0.01 M
in 0.01 M
Reference solution (d) Dissolve 10.0 mg of 4-epianhydrotetracycline hydrochloride CRS in 0.01 M
hydrochloric acid and dilute to 50.0 ml with the same acid.
H3C
HO
H 3C
CH3
HO
N
CH3
CH3
N
CH3
OH
OH
NH2
NH2
OH
OH
OH
O
OH
O
OH
O
O
O
CH3
O
OH-
H+
H3C
O
N
CH3
CH3
H 3C
CH3
N
OH
OH
O
NH2
NH2
OH
OH
5,6
OH
OH
O
O
anhydrotetracycline
O
OH
O
O
Isotetracycine
O
O
Streptomycin Sulfate
Sulphate
streptomycin sulphate
18.0 per cent to 21.5 per cent of sulphate (SO4), calculated with reference to the dried
substance. Dissolve 0.250 g in 100 ml of water R and adjust the solution to pH 11
using concentrated ammonia R. Add 10.0 ml of 0.1 M barium chloride and about 0.5
mg of phthalein purple R. Titrate with 0.1 M sodium edetate adding 50 ml of alcohol R
when the colour of the solution begins to change and continue the titration until the
violet-blue colour disappears.
1 ml of 0.1 M barium chloride is equivalent to 9.606 mg of sulphate (SO4).
Colorimetric test
Dry the substance to be examined and streptomycin sulphate CRS at 60 °C over
diphosphorus pentoxide R at a pressure not exceeding 0.1 kPa for 24 h. Dissolve
0.100 g of the dried substance to be examined in water R and dilute to 100.0 ml with
the same solvent. Prepare a reference solution in the same manner using 0.100 g of
the dried streptomycin sulphate CRS. Place 5.0 ml of each solution separately in two
volumetric flasks and in a third flask place 5 ml of water R. To each flask add 5.0 ml of
0.2 M sodium hydroxide and heat for exactly 10 min in a water-bath. Cool in ice for
exactly 5 min, add 3 ml of a 15 g/l solution of ferric ammonium sulphate R in 0.5 M
sulphuric acid, dilute to 25.0 ml with water R and mix. Exactly 20 min after the addition
of the ferric ammonium sulphate solution measure the absorbance (2.2.25) of the test
solution and the reference solution in a 2 cm cell at the maximum at 525 nm, using as
compensation liquid the solution prepared from 5 ml of water R. The absorbance of the
test solution is not less than 90.0 per cent of that of the reference solution.
Streptomycin Sulfate – BP колориметричен тест
3-hydroxy-2-methyl-4H-pyran-4-one
Sterility (2.6.1). If intended for use in the manufacture of parenteral
dosage forms without a further appropriate sterilisation procedure, it
complies with the test for sterility.
Bacterial endotoxins (2.6.14). If intended for use in the manufacture
of parenteral dosage forms without a further appropriate procedure for
the removal of bacterial endotoxins, not more than 0.25 I.U. of
endotoxin per milligram.
ASSAY :
Carry out the microbiological assay of antibiotics (2.7.2).
Gentamycin Sulfate
Gentamycin Sulfate
A. Dissolve about 10 mg in 1 ml of water R
and add 5 ml of a 400 g/l solution of
sulphuric acid R. Heat on a water-bath for
100 min, cool and dilute to 25 ml with water
R. Examined between 240 nm and 330 nm
(2.2.25), the solution shows no absorption
maximum.
B. Thin-layer chromatography (2.2.27).
Detection Spray
with
ninhydrin
solution R1 and heat at 110 °C for 5
min.
Title:
HPLC Determination of Gentamycin in
Pharmaceutical Dosage Forms by
Postcolumn Derivatization with ophthalaldehyde
Author/s:
Calderon L, Brunetto R, Leon A, et.al.
Reference:
American Laboratory -December 1996;56
- 60
Gentamycin
Several methods have been reported for the determination of therapeutically important AG
antibiotics, including gentamicin. Particularly, methods based on radioenzymatic,
radioimmunoassay, conventional polarographic, spectrophotometric, spectrofluorometric,
nuclear magnetic resonance (NMR), and microbiological measurements lack specificity and
fail to distinguish among different AGs. Recently, HPLC has been presented as an alternative
to the above-mentioned methods. HPLC procedures are generally rapid and precise and
ensure high specificity. The HPLC procedure utilizes reversed-phase or ion-pair reversedphase chromatography; ion-exchange chromatography with different types of detection, such
as fluorescence or UV with pre-column derivatization with o-phthalaldehyde (OPA); and
fluorescence after postcolumn derivatization with OPA or refractive index detection for the
quantification of AGs in body fluids, tissues, raw materials, and pharmaceutical preparations.
Amikacin
Amikacin sulphate is 6-O-(3-amino-3-deoxy-a-Dglucopyranosyl)-4-O-(6-amino-6-deoxy-a-Dglucopyranosyl)-1-N-[(2S)-4-amino-2-hydroxybutanoyl] - 2 - deoxy - D - streptamine sulphate, an
antimicrobial substance obtained from kanamycin A.
Kanamycin Sulphate
kanamycin
IDENTIFICATION
A. Examine by thin-layer chromatography (2.2.27), using a plate coated
with a 0.75 mm layer of the following mixture: mix 0.3 g of carbomer R
with 240 ml of water R and allow to stand, with moderate shaking, for 1 h;
adjust to pH 7 by the gradual addition, with continuous shaking, of dilute
sodium hydroxide solution R and add 30 g of silica gel H R.
Heat the plate at 110 °C for 1 h, allow to cool and use immediately.
Test solution Dissolve 10 mg of the substance to be examined in water
R and dilute to 10 ml with the same solvent.
Reference solution (a) Dissolve 10 mg of kanamycin monosulphate
CRS in water R and dilute to 10 ml with the same solvent.
Reference solution (b) Dissolve 10 mg of kanamycin monosulphate
CRS, 10 mg of neomycin sulphate CRS and 10 mg of streptomycin
sulphate CRS in water R and dilute to 10 ml with the same solvent.
C. Dissolve about 50 mg in 2 ml of water R. Add 1 ml of a 10 g/l solution
of ninhydrin R and heat for a few minutes on a water-bath. A violet
colour develops.
Lincomycin Hydrochloride
Lincomycin hydrochloride consists mainly of the methyl 6,8dideoxy-6-[[[(2S,4R)-1-methyl-4-propylpyrrolidin-2 yl]carbonyl]
amino] - 1 - hio – D - erythro -a- D- galacto - octopyranoside
hydrochloride, an antimicrobial substance produced by
Streptomyces lincolnensis var. lincolnensis or by any other
means.
lincomycin
ASSAY
Examine by gas chromatography (2.2.28), using dotriacontane R as the internal standard.
Internal standard solution. Dissolve 0.200 g of dotriacontane R in chloroform R and dilute to 25.0 ml with
the same solvent.
Test solution (a). Dissolve 0.100 g of the substance to be examined in a 20 g/l solution of imidazole R in
chloroform R and dilute to 100.0 ml with the same solution. Shake until solution is complete. Place 4.0
ml of the solution in a ground-glass-stoppered 15 ml centrifuge tube. Add 1.0 ml of a mixture of 1 volume
of chlorotrimethylsilane R and 99 volumes of N,O-bis( trimethylsilyl)acetamide R and swirl gently.
Position the glass stopper loosely in the tube and heat at 65°C for 30 min.
Test solution (b). Prepare as described for test solution (a) but add 10.0 ml of the internal standard
solution before dissolution of the substance to be examined.
Reference solution. Prepare as described for test solution (a) using 0.100 g of lincomycin hydrochloride
CRS instead of the substance to be examined and adding 10.0 ml of the internal standard solution
before dissolution of the reference substance.
The chromatographic procedure may be carried out using:
— a glass column 1.5 m long and 3 mm in internal diameter packed with silanised diatomaceous earth
for gas chromatography R impregnated with 3 per cent m/m of poly(methylphenylsiloxane) R,
— helium for chromatography R as the carrier gas at a flow rate of about 45 ml per minute,
— a flame-ionisation detector,
maintaining the temperature of the column at 260°C and that of the injection port and of the detector
between 260°C and 290°C. Inject the chosen volume of the test solutions and the reference solution.
Rifamycin Sodium
C37H46NNaO12
Примеси
R = -O-CH2-CO2H, R´ = -OH:
rifamycin B,
R = O, R´ = O: rifamycin S,
R = -O-CO-CH2-O-, R´ = O:
rifamycin O.
erythromycin
•sum of the contents of
erythromycin A,
erythromycin B and
erythromycin C: 93.0 per
cent to 102.0 per cent
(anhydrous substance),
•erythromycin B:
maximum 5.0 per cent,
•erythromycin C:
maximum 5.0 per cent.
erythromycin
Specific
optical
rotation (2.2.7)
- 71 to - 78 (anhydrous
substance).
Dissolve 1.00 g in
ethanol R and dilute to
50.0 ml with the same
solvent. The specific
optical
rotation
is
determined at least 30
min after preparing the
solution.
Related substances
Liquid chromatography (2.2.29).
Column:
—size: l = 0.25 m, Ø = 4.6 mm,
—stationary phase: styrene-divinylbenzene copolymer R (8 µm)
with a pore size of 100 nm,
—temperature: 70 °C using a water-bath for the column and at
least one-third of the tubing preceding the column.
Mobile phase To 50 ml of a 35 g/l solution of dipotassium
hydrogen phosphate R adjusted to pH 9.0 ± 0.05 with dilute
phosphoric acid R, add 400 ml of water R, 165 ml of 2-methyl-2propanol R and 30 ml of acetonitrile R, and dilute to 1000 ml with
water R.
Flow rate 2.0 ml/min.
Detection Spectrophotometer at 215 nm.
Run time 5 times the retention time of erythromycin A.
Relative retention with reference to erythromycin A (retention
time = about 15 min): impurity A = about 0.3; impurity B = about
0.45; erythromycin C = about 0.5; impurity C = about 0.9;
impurity D = about 1.4; impurity F = about 1.5; erythromycin B =
about 1.8; impurity E = about 4.3.
System suitability Reference solution (c):
—resolution: minimum 0.8 between the peaks due to impurity B
and erythromycin C and minimum 5.5 between the peaks due to
impurity B and erythromycin A. If necessary, adjust the
concentration of 2-methyl-2-propanol in the mobile phase or
reduce the flow rate to 1.5 ml or 1.0 ml/min.
clarithromycin
Clarithromycin is a macrolide
antibiotic used to treat pharyngitis,
tonsillitis, acute maxillary sinusitis,
acute bacterial exacerbation of
chronic
bronchitis,
pneumonia
(especially atypical pneumonias
associated
with
Chlamydia
pneumoniae or TWAR), skin and skin
structure infections, and, in HIV and
AIDS patients to prevent, and to
treat, disseminated Mycobacterium
avium complex (MAC). In addition, it
is sometimes used to treat
Legionellosis.
Clarithromycin is available under
several brand names, for example
Biaxin, Klacid, Claripen and
Claridar.
Azithromycin is an azalide, a subclass of
macrolide antibiotics. Azithromycin (brand
names Zithromax® in Italy and the United
States; Vinzam® / Zitromax® in Spain;
Zmax®; Sumamed®; Aztrin®, Zitrocin®,
Azibiot®) is one of the world's best-selling
antibiotics, and is derived from erythromycin;
however,
it
differs
chemically
from
erythromycin in that a methyl-substituted
nitrogen atom is incorporated into the lactone
ring, thus making the lactone ring 15membered. Azithromycin is used to treat
certain bacterial infections, most often bacteria
causing middle ear infections, tonsillitis, throat
infections, laryngitis, bronchitis, pneumonia
and sinusitis. It is also effective against certain
sexually transmitted infectious diseases, such
as non-gonococcal urethritis and cervicitis.
Recent studies have also indicated it to be
effective against late-onset asthma, but these
findings are controversial and not widely
accepted as of yet.
azithromycin
Telithromycin is the first ketolide
antibiotic to enter clinical use. It is
used to treat mild to moderate
respiratory infections. Telithromycin
is sold under the brand name of
Ketek®.
Telithromycin is a semi-synthetic
erythromycin derivative. It is created
by substituting the cladinose sugar
with a ketogroup and adding a
carbamate ring in the lactone ring.
An alkyl-aryl moiety is attached to
this carbamate ring. Furthermore, the
carbon at position 6 has been
methylated, like in clarithromycin, to
achieve better acid-stability.
nystatin
C47H75NO17
926
Content
Minimum 4400 IU/mg (dried substance)
and
minimum
5000
IU/mg
(dried
substance)
if intended for oral
administration.
PRODUCTION
If nystatin is not intended for cutaneous
administration, the method of manufacture
is validated to demonstrate that the
product, if tested, would comply with the
following test.
Abnormal toxicity (2.6.9)
Inject intraperitoneally into each mouse a
quantity equivalent to not less than 600 IU
suspended in 0.5 ml of a 5 g/l solution of
acacia R.
CHARACTERS
Appearance
Yellow or slightly brownish powder,
hygroscopic.
Solubility
Practically insoluble in water, freely soluble
in dimethylformamide and in dimethyl
sulphoxide, slightly soluble in methanol,
practically insoluble in alcohol.