别名：氨苄青霉素三水酸;氨苄西林三水酸;Ampicillin trihydrate;Aminobenzylpenicillin trihydrate

氨苄西林（Ampicillin）

适应症：用以治疗敏感的G+菌和流感杆菌、伤寒杆菌、淋球菌、脑膜炎球菌、大肠杆菌等G所致的呼吸道感染、胃肠道感染、尿路感染、软组织感染、脑膜炎、败血症、心内膜炎等。

不良反应及注意事项：不良反应与青霉素相仿，以过敏反应较为多见。传染性单核细胞增多症、巨细胞病毒感染、淋巴细胞白血病、淋巴瘤等病人应用本品时易发生皮疹。因此，本品不能用于这些病人。大剂量氨苄西林静脉给药可发生抽搐等神经系统毒性症状。

类别：抗生素

Ampicillin Trihydrate
C16H19N3O4S,3H2O  403.5

Definition
Ampicillin trihydrate contains not less than 96.0 per cent and not more than the equivalent of 100.5 per cent of (2S,5R,6R)-6-[[(2R)-2-amino-2-phenylacetyl]amino]-3,3-dimethyl-7-oxo-4-thia-1-azabicyclo[3.2.0]heptane-2-carboxylic acid, calculated with reference to the anhydrous substance.

Characters
A white, crystalline powder, slightly soluble in water, practically insoluble in alcohol, in ether and in fatty oils. It dissolves in dilute solutions of acids and of alkali hydroxides.

Identification
First identification
A, D.
Second identification
B, C, D.
A.Examine by infrared absorption spectrophotometry (2.2.24), comparing with the spectrum obtained with ampicillin trihydrate CRS.
B.Examine by thin-layer chromatography (2.2.27), using silanised silica gel H R as the coating substance.

Test solution
Dissolve 25 mg of the substance to be examined in 10 ml of sodium hydrogen carbonate solution R.

Reference solution (a)
Dissolve 25 mg of ampicillin trihydrate CRS in 10 ml of sodium hydrogen carbonate solution R.

Reference solution (b)
Dissolve 25 mg of amoxicillin trihydrate CRS and 25 mg of ampicillin trihydrate CRS in 10 ml of sodium hydrogen carbonate solution R.

Apply separately to the plate 1 ml of each solution. Develop over a path of 15 cm using a mixture of 10 volumes of acetone R and 90 volumes of a 154 g/l solution of ammonium acetate R, the pH of which has been adjusted to 5.0 with glacial acetic acid R. Allow the plate to dry in air and expose it to iodine vapour until the spots appear. Examine in daylight. The principal spot in the chromatogram obtained with the test solution is similar in position, colour and size to the principal spot in the chromatogram obtained with reference solution (a). The test is not valid unless the chromatogram obtained with reference solution (b) shows 2 clearly separated spots.

C.Place about 2 mg in a test-tube about 150 mm long and 15 mm in diameter. Moisten with 0.05 ml of water  R and add 2 ml of sulphuric acid-formaldehyde reagent R. Mix the contents of the tube by swirling; the solution is practically colourless. Place the test-tube in a water-bath for 1 min; a dark yellow colour develops.

D.It complies with the test for water (see Tests).

Tests
Appearance of solution
Dissolve 1.0 g in 10 ml of 1M hydrochloric acid. Separately dissolve 1.0 g in 10 ml of dilute ammonia R2. Immediately after dissolution, the solutions are not more opalescent than reference suspension II (2.2.1).

pH (2.2.3)
Dissolve 0.1 g in carbon dioxide-free water  R and dilute to 40 ml with the same solvent. The pH of the solution is 3.5 to 5.5.

Specific optical rotation (2.2.7)
Dissolve 62.5 mg in water  R and dilute to 25.0 ml with the same solvent. The specific optical rotation is +280° to +305°, calculated with reference to the anhydrous substance.

Related substances
Examine by liquid chromatography (2.2.29) as described under Assay. Inject reference solution (c) and elute isocratically. Inject freshly prepared test solution (b) and start the elution isocratically. Immediately after elution of the ampicillin peak start the following linear gradient. If the mobile phase composition has been adjusted to achieve the required resolution, the adjusted composition will apply at time zero in the gradient.

Equilibrate the column with the originally chosen mobile phase for 15 min. Inject mobile phase A and use the same elution gradient to obtain a blank. In the chromatogram obtained with test solution (b), the area of any peak, apart from the principal peak and any peak observed in the blank chromatogram, is not greater than the area of the principal peak in the chromatogram obtained with reference solution (c) (1.0 per cent).

N,N-Dimethylaniline (2.4.26, Method B)
Not more than 20 ppm.

Water (2.5.12)
12.0 per cent to 15.0 per cent, determined on 0.100 g by the semi-micro determination of water.

Sulphated ash (2.4.14)
Not more than 0.5 per cent, determined on 1.0 g.

Assay
Examine by liquid chromatography (2.2.29).

Test solution (a)
Dissolve 31.0 mg of the substance to be examined in mobile phase A and dilute to 50.0 ml with the same solvent.

Test solution (b)
Dissolve 31.0 mg of the substance to be examined in mobile phase A and dilute to 10.0 ml with the same solvent.

Reference solution (a)
Dissolve 27.0 mg of anhydrous ampicillin CRS in mobile phase A and dilute to 50.0 ml with the same solvent.

Reference solution (b)
Dissolve 2.0 mg of cefradine CRS in mobile phase A and dilute to 50 ml with the same solvent. To 5.0 ml of this solution add 5.0 ml of reference solution (a).

Reference solution (c)
Dilute 1.0 ml of reference solution (a) to 20.0 ml with mobile phase A.

Reference solution (d)
Dilute 1.0 ml of reference solution (c) to 25.0 ml with mobile phase A.

The chromatographic procedure may be carried out using:
a column 0.25M long and 4.6 mm in internal diameter packed with octadecylsilyl silica gel for chromatography R (5 mm),
as mobile phase at a flow rate of 1.0 ml/min:
Mobile phase A A mixture of 0.5 ml of dilute acetic acid R, 50 ml of 0.2M potassium dihydrogen phosphate R, 50 ml of acetonitrile R diluted to 1000 ml with water  R,
Mobile phase B A mixture of 0.5 ml of dilute acetic acid R, 50 ml of 0.2M potassium dihydrogen phosphate R and 400 ml of acetonitrile R diluted to 1000 ml with water  R,
as detector a spectrophotometer set at 254 nm,
a 50 ml loop injector.

Equilibrate the column with a mobile phase with ratio A:B of 85:15. Inject reference solution (b). The test is not valid unless the resolution between the two principal peaks is at least 3.0. If necessary, adjust the ratio A:B of the mobile phase. The mass distribution ratio for the first peak (ampicillin) is 2.0 to 2.5. Inject reference solution (d). Adjust the system to obtain a peak with a signal-to-noise ratio of at least 3. Inject reference solution (a) 6 times. The test is not valid unless the relative standard deviation for the area of the principal peak is at most 1.0 per cent. Inject alternately test solution (a) and reference solution (a).

Calculate the percentage content of ampicillin.

Storage
Store in an airtight container , at a temperature not exceeding 30°C.

Action and use
Antibacterial.

Preparations
Ampicillin Capsules
Ampicillin Oral Suspension
Co-fluampicil Capsules
Co-fluampicil Oral Suspension