Doxycycline Calcium Oral Suspension

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

Doxycycline Calcium Oral Suspension is prepared from Doxycycline Hyclate and contains one or more suitable buffers, colors, diluents, flavors, and preservatives. It contains the equivalent of NLT 90.0% and NMT 125.0% of the labeled amount of doxycycline (C₂₂H₂₄N₂O₈).

2 IDENTIFICATION

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

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

3 ASSAY

PROCEDURE

Protect solutions containing doxycycline from light.

Solution A: Transfer 3.1 g of monobasic potassium phosphate, 0.5 g of edetate disodium, and 0.5 ml. of triethylamine to a 1000-ml volumetric flask. Add about 850 ml of water and mix. Dilute with water to volume and adjust with 1 N sodium hydroxide to a pH of 8.5 ± 0.1. Pass through a suitable filter of 0.224mu*m pore size

Solution B: Methanol

Mobile phase: See Table 1.

Diluent: 0.01 N hydrochloric acid

Standard solution: 0.12 mg/ml, of USP Doxycycline Hyclate RS in Diluent. Sonicate as needed to dissolve.

Sample solution: Nominally 0.1 mg/mL of doxycycline in Diluent, prepared as follows. Transfer an adequate amount of Oral Suspension, freshly mixed and free from air bubbles, to a suitable volumetric flask. Add 80% of the final volume of Diluent, sonicate for about 15 min, and dilute with Diluent to volume. Centrifuge a portion of the solution for 10 min at 3000 rpm and use the supernatant for analysis.

Chromatographic system

(See Chromatography (621). System Suitability)

Mode: LC

Detector: UV 270 nm. For Identication A, use a diode array detector in the range of 200-400 nm.

Column: 2.1-mm × 5-cm; 1.7-µm packing L7

[Note—A 1.7-µm guard column with packing L7 was used during method validation.]

Column temperature: 60

Flow rate: 0.6 mL/min

Injection volume: 5 µL

System suitability

Sample: Standard solution

Suitability requirements

Tailing factor: NMT 1.5

Relative standard deviation: NMT 2.0%

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amount of doxycycline (C₂₂H₂₄N₂O₈) in the portion of Oral Suspension taken:

Result = (r_U/(r_S) × (C_S /C_U) × P x F x 100

r_U = peak response from the Sample solution

r_S = peak response from the Standard solution

C_S = concentration of USP Doxycycline Hyclate RS, in the Stardard solution (mg/ml)

C_U = nominal concentration of doxycycline in the Sample sulation (mg/ml)

P = potency of doxycycline in USP Doxycycline Hyclate RS (µg/mg)

F = conversion factor 0.001 mg/μg

Acceptance criteria: 90.0%-125.0%

4 PERFORMANCE TESTS

UNIFORMITY OF DOSAGE UMITS (905)

For single-unit containers

Acceptance criteria: Meets the requirements

DELIVERABLE VOLUME (698): Meets the requirements.

5 IMPURITIES

Delete the following:

ORGANIC IMPURITIES

Protect solutions containing doxycycline from light.

Mobile phase, Diluent, and Chromatographic system: Proceed as directed in the Assay

System suitability stock solution 1: 1 mg/ml each of USP Doxycycline Related Compound A RS and USP Methacycline Hydrochloride RS in Diluent

System suitability stock solution 2: 1.2 mg/ml. of USP Doxycycline Hyclate RS in Diluent

System suitability solution: Transfer 5 mL of System suitability stock solution 2 to a 25-ml, volumetric flask, heat on a steam bath for 60 min, and evaporate to dryness on a hot plate, taking care not to char the residue. Dissolve the residue in Diluent, add 0.5 mL of System suitability stock solution 1, and dilute with Diluent to volume. Pass through a suitable filter of 0.20-µm pore size and use the filtrate. This solution contains a mixture of 4-epidoxycycline, doxycycline related compound A, methacycline, and doxycycline. (Nore-The solution is stable up to 14 days when stored in a refrigerator]

Standard solution: 2.3 µg/mL of USP Doxycycline Hyclate RS in Diluent

Sample solution: Nominally 2.0 mg/ml, of doxycycline in Diluent, prepared as follows. Transfer an adequate amount of Oral Suspension, freshly mixed and free from air bubbles, to a suitable volumetric flask. Add 60% of the final volume of Diluent, sonicate for about 15 min, and dilute with Diluent to volume. Centrifuge a portion of the solution for 10 min at 3000 rpm and use the supernatant for analysis.

System suitability

Samples: System suitability solution and Standard solution

Suitability requirements

Resolution: NLT 1.5 between methacycline and 4-epidoxycycline, NLT 1.5 between 4-epidoxycycline and doxycycline related compound A and NLT 2.0 between doxycycline related compound A and doxycycline, System suitability solution

Relative standard deviation: NMT 5.0% for doxycycline, Standard solution

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of each impurity in the portion of Oral Suspension taken:

Result = (r_U/(r_S) × (C_S /C_U) × P x F x 100

r_U = peak response of each impurity from the Sample solution

r_S = peak response of doxycycline from the Standard solution

C_S = concentration of USP Doxycycline Hyclate RS, in the Stardard solution (mg/ml)

C_U = nominal concentration of doxycycline in the Sample sulation (mg/ml)

P = potency of doxycycline in USP Doxycycline Hyclate RS (µg/mg)

F = conversion factor 0.001 mg/μg

Acceptance criteria: See Table 2. Disregard peaks less than 0.1%.

^a (4S,4aR,55,5aR, 12aS)-4-(Dimethylamino)-1,4,4,5,58,6,11,12a-octahydro-3,5,10,12,12a-pentahydroxy-6-methylene-1,11-dioxo-2-naphthacenecarboxamide.

^b (4R,4aR,55,5aR,6,12aS)-4-(Dimethylamino)-1,4,4,5,5a,6,11,12a-octahydro-3,5,10,12,12a-pentahydroxy-6-methyl-1,11-dioxo-2-naphthacenecarboxamide.

^c(4R,4aR,5S,5aR,6R,12aS)-4-(Dimethylamino)-1,4,4a,5,5a,6,11,12a-octahydro-3,5,10,12,12a-pentahydroxy-6-methyl-1,11-dioxo-2- naphthacenecarboxamide.

^d (4S,4aR,5S,5aR,6S,12aS)-4-(Dimethylamino)-1,4,4a,5,5a,6,11,12a-octahydro-3,5,10,12,12a-pentahydroxy-6-methyl-1,11-dioxo-2-naphthacenecarboxamide.

6 SPECIFIC TESTS

H(791): 6.5-8.0

7 ADDITIONAL REQUIREMENTS

PACKAGING AND STORAGE: Preserve in tight, light-resistant containers.