Butorphanol Tartrate Nasal Spray

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

Butorphanol Tartrate Nasal Spray is an aqueous solution of butorphanol tartrate for administration as a metered spray to the nasal mucosa. It contains the equivalent of NLT 90.0% and NMT 110.0% of the labeled amount of butorphanol tartrate (C₂₁H₂₉NO₂ · C₄H₆O₆).

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. THIN-LAYER CHROMATOGRAPHIC IDENTIFICATION TEST (201)

Standard solution: 1.0 mg/mL of USP Butorphanol Tartrate RS in methanol

Sample solution: Prepare a composite solution by pooling the contents of three containers of Nasal Spray into a suitable vessel. Transfer 1.0 mL of pooled sample to a 10-mL volumetric flask, and dilute with methanol to volume.

Developing solvent system: Chloroform, methanol, benzene, and ammonium hydroxide (17:5:4:1)

[CAUTION-Prepare in a hood while wearing appropriate safety gloves, lab coat, and protective eyewear.]

Spray reagent: Prepare a 1-in-10 solution of chloroplatinic acid in water. To 0.5 mL of this solution, add 33 mL of water and 1 g of potassium iodide. Prepare fresh daily.

Analysis

Samples: Standard solution and Sample solution

Proceed as directed in the chapter, except spray the plate with Spray reagent.

Acceptance criteria: The typical R_F value is 0.7 for butorphanol tartrate.

3 ASSAY

3.1 PROCEDURE

Buffer: 3.4 g/L of 0.025 M monobasic potassium phosphate. Filter.

Mobile phase: Acetonitrile, triethylamine, and Buffer (15:2:85). Mix thoroughly, and adjust with 85.0% phosphoric acid to a pH of 3.0 ± 0.1.

Standard solution: 0.2 mg/mL of USP Butorphanol Tartrate RS in Mobile phase. Mix, and filter, discarding the first 2 mL of the filtrate. The Standard solution is stable for at least 108 h.

Sample solution: Nominally 0.2 mg/mL of butorphanol tartrate in Mobile phase prepared as follows. Prepare a composite solution by pooling a minimum of four containers of Nasal Spray into a suitable glass vessel. Transfer the equivalent of 20 mg of butorphanol tartrate to a 100-mL volumetric flask. Dilute with Mobile phase to volume, mix, and filter, discarding the first 2 mL of the filtrate.

Chromatographic system

Mode: LC

Detector: UV 280 nm

Columns

Analytical: 4.6-mm × 15-cm; 5-µm packing L11

Guard: 4.6-mm × 1-cm; 5-µm packing L11

Column temperature: 30°

Flow rate: 2.0 mL/min

Injection volume: 20 µL

System suitability

Sample: Standard solution

Suitability requirements

Tailing factor: NMT 2.0

Relative standard deviation: NMT 2.0%

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amount of butorphanol tartrate (C₂₁H₂₉NO₂ · C₄H₆O₆) in the portion of Nasal Spray taken:

Result = (r_U/r_S) × (C_S/C_U) × 100

r_U = peak response from the Sample solution

r_S = peak response from the Standard solution

C_S = concentration of USP Butorphanol Tartrate RS in the Standard solution (mg/mL)

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

Acceptance criteria: 90.0%–110.0%

4 IMPURITIES

4.1 ORGANIC IMPURITIES

Buffer: Prepare as directed in the Assay.

Mobile phase: Acetonitrile, triethylamine, and Buffer (15:5.1:85). Mix thoroughly, and adjust with 85.0% phosphoric acid to a pH of 3.0 ± 0.1.

Standard solution: 0.005 mg/mL of USP Butorphanol Tartrate RS

Sensitivity solution: Transfer 2.5 mL of the Standard solution to a 50-mL volumetric flask, and dilute with water to volume. Do not filter.

Sample solution: Nominally 1 mg/mL of butorphanol tartrate in water prepared as follows. Prepare a composite solution by pooling a minimum of four containers of Nasal Spray into a suitable glass vessel. Transfer the equivalent of 50 mg of butorphanol tartrate to a 50-mL volumetric flask. Dilute with water to volume. Do not filter.

Chromatographic system

Mode: LC

Detector: UV 280 nm

Columns

Analytical: 4.6-mm × 25-cm; 5-µm packing L11

Guard: 4.6-mm × 1-cm; 5-µm packing L11

Column temperature: 40°

Flow rate: 2.0 mL/min

Injection volume: 60 µL

Run time: 40 min

System suitability

Samples: Standard solution and Sensitivity solution

Relative standard deviation: NMT 10.0%, Standard solution

Sensitivity: The peak height for butorphanol tartrate is ≥3× the baseline noise, Sensitivity solution

Analysis

Samples: Standard solution and Sample solution

Record the chromatograms, and measure the responses for the butorphanol tartrate peak in the Standard solution, and for all known and unknown related compounds in the Sample solution.

Calculate the percentage of each related compound (see Table 1) and each unknown impurity in the portion of Nasal Spray taken:

Result = (r_U/r_S) × (C_S/C_U) × 100

r_U = peak response from the Sample solution

r_S = peak response from the Standard solution

C_S = concentration of USP Butorphanol Tartrate RS in the Standard solution (mg/mL)

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

Table 1

5 SPECIFIC TESTS

MICROBIAL ENUMERATION TESTS (61) and TESTS FOR SPECIFIED MICROORGANISMS (62): The total aerobic microbial count does not exceed 10³ cfu/g or mL, and the total combined molds and yeasts count does not exceed 102 cfu/g or mL. It meets the requirements of the tests for absence of Staphylococcus aureus and Pseudomonas aeruginosa.

PH (791): 4.0-6.0

OSMOLALITY AND OSMOLARITY (785): 252-292 mOsmol/kg

6 ADDITIONAL REQUIREMENTS

PACKAGING AND STORAGE: Preserve in tight containers at controlled room temperature. Store at 25°; excursions permitted between 15° and 30°.

USP REFERENCE STANDARDS (11)

USP Butorphanol Tartrate RS