Lactulose Solution

This article is compiled based on the United States Pharmacopeia (USP) – 2025 Edition

Issued and maintained by the United States Pharmacopeial Convention (USP)

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1 DEFINITION

Lactulose Solution is a solution in water prepared from Lactulose Concentrate. It contains NLT 90.0% and NMT 110.0% of the labeled amount of lactulose (C₁₂H₂₂O₁₁).

2 IDENTIFICATION

A. The retention time of the major peak of the Sample solution corresponds to that of the Standard solution, as obtained in the Assay.

B. Sample solution: Dilute a portion of Solution with water (1 in 20).

Analysis: Add a few drops of the Sample solution to 5 mL of hot alkaline cupric tartrate TS.

Acceptance criteria: A red precipitate of cuprous oxide is formed.

3 ASSAY

Procedure

Buffer: 1.15 g/L of monobasic sodium phosphate in water

Mobile phase: Acetonitrile and Buffer (82:18). Ensure that the concentration of acetonitrile in the Mobile phase is between 78% and 85% to obtain appropriate retention times.

Standard solution: 40 mg/mL of USP Lactulose RS, 4.8 mg/mL of USP Anhydrous Lactose RS, and 3.2 mg/mL of USP Epilactose RS in a mixture of acetonitrile and water (1:1)

Sample solution: Nominally equivalent to 40 mg/mL of lactulose prepared as follows. Transfer a quantity of Solution containing 2.0 g of lactulose to a 50-mL volumetric flask, and dissolve in 20 mL of water. Add 25.0 mL of acetonitrile, allow the solution to reach ambient temperature, and dilute with water to volume.

Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: Refractive index

Column: 4.6-mm × 15-cm; 3-μm packing L8

Temperatures

Column: 40 ± 1°

Detector: 40 ± 1°

Flow rate: 1.3 mL/min

Injection volume: 20 μL

System suitability

Sample: Standard solution

[Note—The relative retention times are given in Table 1.]

Suitability requirements

Resolution: NLT 1.5 between lactulose and lactose; NLT 0.9 between lactulose and epilactose

Relative standard deviation: NMT 2.0% for the main peak

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amount of lactulose (C₁₂H₂₂O₁₁) in the portion of Solution taken:

Result = (r /r ) × (C /C ) × 100

r = peak response from the Sample solution

r = peak response from the Standard solution

C = concentration of USP Lactulose RS in the Standard solution (mg/mL)

C = nominal concentration of lactulose in the Sample solution (mg/mL)

Acceptance criteria: 90.0%–110.0%

4 PERFORMANCE TESTS

Uniformity of Dosage Units 〈905〉

Oral Solution packaged in single-unit containers

Acceptance criteria: Meets the requirements

5 IMPURITIES

5.1 Organic Impurities

Buffer, Mobile phase, Sample solution, Chromatographic system, and System suitability: Proceed as directed in the Assay. To evaluate the

Suitability requirements, use the Standard solution prepared as directed in the Assay.

Standard solution: 6.4 mg/mL of USP Galactose RS, 4.8 mg/mL of USP Anhydrous Lactose RS, 3.2 mg/mL of USP Epilactose RS, 1.2 mg/mL of USP Tagatose RS, and 0.4 mg/mL of USP Fructose RS in a mixture of acetonitrile and water (1:1)

5.2 Analysis

Samples: Standard solution and Sample solution

Calculate the percentages of galactose, lactose, epilactose, tagatose, and fructose, if found, in the portion of Solution taken:

Result = (r_U/r_S)x(C_S/C_U) × 100

r_U = peak response of the relevant related compound from the Sample solution

r_S = peak response of the relevant related compound from the Standard solution

C_S = concentration of the relevant USP Reference Standard in the Standard solution (mg/mL)

C_U = nominal concentration of lactulose in the Sample solution (mg/mL)

Acceptance criteria: See Table 1.

Table 1

6 SPECIFIC TESTS

Microbial Enumeration Tests 〈61〉 and Tests for Specified Microorganisms 〈62〉: The total bacterial count is NMT 10² cfu/g of lactulose, and the tests for Salmonella species and Escherichia coli are negative.

pH 〈791〉: 2.5–6.5, after 15 min of contact with the electrodes

7 ADDITIONAL REQUIREMENTS

Packaging and Storage: Preserve in tight containers, preferably at a temperature between 2° and 30°. Avoid subfreezing temperatures.

USP Reference Standards 〈11〉

USP Epilactose RS

USP Fructose RS

USP Galactose RS

USP Anhydrous Lactose RS

USP Lactulose RS

USP Tagatose RS