Dorzolamide Hydrochloride Ophthalmic 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

Dorzolamide Hydrochloride Ophthalmic Solution is a sterile, isotonic, buffered, slightly viscous, aqueous solution of Dorzolamide Hydrochloride. It contains NLT 90.0% and NMT 110.0% of the labeled amount of dorzolamide (C₁₀H₁₆N₂O₄S₃). It may contain a suitable preservative.

2 IDENTIFICATION

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A. The UV spectrum of the major peak of the Sample solution corresponds to that of the Standard solution, as obtained in the Assay _{(USP 1-Dec-2021)}

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

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PROCEDURE

Buffer: Fill a 1-L volumetric flask approximately two-thirds full of water. Add 2.0 mL of phosphoric acid, and dilute with water to 900 mL..

Adjust with triethylamine to a pH of 3.0, and dilute with water to volume.

Mobile phase: Acetonitrile and Buffer (5:95)

Standard solution: 0.11 mg/mL of USP Dorzolamide Hydrochloride RS and 0.5 µg/mL each of USP Dorzolamide Related Compound B RS and USP Dorzolamide Related Compound D RS in Mobile phase

Sample solution: Nominally 0.1 mg/mL of dorzolamide in Mobile phase, from Ophthalmic Solution

Chromatographic system

(See Chromatography (621), System Suitability.)

Mode: LC

Detector: UV 253 nm. For Identification A, use a diode array detector in the range of 200-400 nm. _{(USP 1-Dec-2021)}

Column: 4.6-mm x 25-cm; 5-µm packing 17

Flow rate: 1 mL/min

Injection volume: 20 µL

System suitability

Sample: Standard solution

[NOTE-See Table 1 for the relative retention times.]

Suitability requirements

Resolution: NLT 3.0 between dorzolamide and dorzolamide related compound D; and NLT 3.0 between dorzolamide and dorzolamide related compound B

Tailing factor: NMT 1.8 for dorzolamide

Relative standard deviation: NMT 2.0% for dorzolamide

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amount of dorzolamide (C₁₀H₁₆N₂O₄S₃) in the portion of Ophthalmic Solution taken:

Result = (r_u /r_s ) × (C_s /C_u ) × (M_r1 /M_r2 ) × 100

r_u = peak response of dorzolamide from the Sample solution

r_s = peak response of dorzolamide from the Standard solution

C_s = concentration of USP Dorzolamide Hydrochloride RS in the Standard solution (mg/mL)

C_u = nominal concentration of dorzolamide in the Sample solution (mg/mL)

M_r1 = molecular weight of dorzolamide, 324.43 _{(USP 1-Dec-2021)}

M_r2 = molecular weight of dorzolamide hydrochloride, 360.89 _{(USP 1-Dec-2021)}

Acceptance criteria: 90.0%–110.0%

4 IMPURITIES

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ORGANIC IMPURITIES

Buffer, (USP 1-Dec-2021) Mobile phase, and _{(USP 1-Dec-2021)}

Sample solution (USP 1-Dec-2021): Prepare as directed in the Assay.

Standard solution A: Use the Standard solution as prepared in the Assay.

Standard solution B: 0.5 µg/mL each of USP Dorzolamide Related Compound B RS and USP Dorzolamide Related Compound D RS in Mobile phase _{(USP 1-Dec-2021)}

Chromatographic system: Proceed as directed in the Assay, except for the Run time.

Run time: NLT 1.4 times the retention time of dorzolamide

System suitability

Sample: Standard solution A

Suitability requirements

Resolution: NLT 3.0 between dorzolamide and dorzolamide related compound D; NLT 3.0 between dorzolamide and dorzolamide related compound B

Tailing factor: NMT 1.8 for dorzolamide

Relative standard deviation: NMT 2.0% for dorzolamide _{(USP 1-Dec-2021)}

Analysis

Samples: Standard solution A, Standard solution B. _{(USP 1-Dec-2021)} and Sample solution

Calculate the percentage of dorzolamide related compound D in the portion of Ophthalmic Solution taken:

Result = (r_u /r_s ) × (C_s /C_u ) × (M_r1 /M_r2 ) × 100

r_u = peak area of dorzolamide related compound D from the Sample solution

r_s = peak area of dorzolamide related compound D from Standard solution B _{(USP 1-Dec-2021)}

C_s = concentration of USP Dorzolamide Related Compound D RS in Standard solution B _{(USP 1-Dec-2021)} (mg/mL)

C_u = nominal concentration of dorzolamide in the Sample solution (mg/mL)

M_r1 = molecular weight of dorzolamide, 324.43 _{(USP 1-Dec-2021)}

M_r2 = molecular weight of dorzolamide related compound D, 332.83 _{(USP 1-Dec-2021)}

Calculate the percentage of dorzolamide related compound B in the portion of Ophthalmic Solution taken:

Result = (r_u /r_s ) × (C_s /C_u ) × (M_r1 /M_r2 ) × 100

r_u = peak area of dorzolamide related compound B from the Sample solution

r_s = peak area of dorzolamide related compound B from Standard solution B _{(USP 1-Dec-2021)}

C_s = concentration of USP Dorzolamide Related Compound B RS in Standard solution B _{(USP 1-Dec-2021)} (mg/mL)

C_u = nominal concentration of dorzolamide in the Sample solution (mg/mL)

M_r1 = molecular weight of dorzolamide, 324.43 _{(USP 1-Dec-2021)}

M_r2 = molecular weight of dorzolamide related compound B, 360.89 _{(USP 1-Dec-2021)}

Calculate the percentage of each individual unspecied impurity in the portion of Ophthalmic Solution taken:

Result = (r_u /r_s ) × (C_s /C_u ) × (M_r1 /M_r2 ) × 100

r_u = peak area of each individual unspecied impurity from the Sample solution

r_s = peak area of dorzolamide from Standard solution A _{(USP 1-Dec-2021)}

C_s = concentration of USP Dorzolamide Hydrochloride RS in Standard solution A _{(USP 1-Dec-2021)} (mg/mL)

C_u = nominal concentration of dorzolamide in the Sample solution (mg/mL)

M_r1 = molecular weight of dorzolamide, 324.43 _{(USP 1-Dec-2021)}

M_r2 = molecular weight of dorzolamide hydrochloride, 360.89 _{(USP 1-Dec-2021)}

Acceptance criteria: See Table 1.

Table 1

^a The sum of dorzolamide related compound D, dorzolamide related compound B, and all unspecied impurities.

5 SPECIFIC TESTS

Sterility Tests 〈71〉: Meets the requirements

pH 〈791〉: 5.4–5.9

Add the following:

Other Requirements: It meets the requirements in Ophthalmic Products—Quality Tests 〈771〉. _{(USP 1-Dec-2021)}

6 ADDITIONAL REQUIREMENTS

Packaging and Storage: Preserve in tight containers protected from light at controlled room temperature.

Change to read:

USP Reference Standards 〈11〉

USP Dorzolamide Hydrochloride RS

USP Dorzolamide Related Compound B RS

(4RS,6SR _{(USP 1-Dec-2021)} )-4-(Ethylamino)-6-methyl-5,6-dihydro-4H-thieno[2,3-b]thiopyran-2-sulfonamide 7,7-dioxide hydrochloride.

C₁₀H₁₆N₂O₄S3 · HCl         360.89 _{(USP 1-Dec-2021)}

USP Dorzolamide Related Compound D RS

(4S,6S)-4-Amino-6-methyl-5,6-dihydro-4H-thieno[2,3-b]thiopyran-2-sulfonamide 7,7-dioxide hydrochloride.

C₈H₁₂N₂O₄S₃ · HCl           332.83 _{(USP 1-Dec-2021)}