Aripiprazole

Aripiprazole USP Monograph Methods

Overview

Aripiprazole is an atypical antipsychotic and a partial dopamine agonist. It is primarily used in the treatment of schizophrenia, bipolar disorder, major depressive disorder, tic disorders, and irritability associated with autism. Aripiprazole was first approved by the U.S. Food and Drug Administration in November 2002 for schizophrenia and by the European Medicines Agency in June 2004 for acute manic and mixed episodes associated with bipolar disorder.

Common commercial brand Names:
Abilify and Aripiprex

Aripiprazole was developed by Otsuka in Japan. In the United States, Otsuka America markets it jointly with Bristol-Myers Squibb. In 2010, sales were $4.6 billion globally; the patent expired in 2015.

In this Compilation, we have used the USP 40–NF 35 experimental Conditions for Aripiprazole in the following Areas:

  • Identification — FTIR
  • Assay — HPLC (gradient method)
  • Related Substances — HPLC (gradient method)

The HPLC methods are gradient methods, thus they are nonscalable. The same chromatographic conditions are used for methods in both the assay and related substances, and a full validation protocol can be found using these USP Reference Standards: USP Aripiprazole RS and USP Aripiprazole Related Compound F RS.

 

Identification and Assay

DEFINITION

Aripiprazole contains not less than (NLT) 98.0% and not more than (NMT) 102.0% of aripiprazole (C23H27Cl2N3O2), calculated on the dried basis.


IDENTIFICATION—FTIR <197K>

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


ASSAY—HPLC (gradient method)
Procedure (protect the solutions from light):

Diluent: Acetonitrile, methanol, water, and acetic acid (30:10:60:1)

Solution A: Acetonitrile and 0.05% trifluoroacetic acid (10:90)
Solution B: Acetonitrile and 0.05% trifluoroacetic acid (90:10)

Gradient: See table.

We have used a Purospher® STAR RP-18 endcapped (3 µm) 100 x 4.6 mm (Catalogue Number 1.50469).
This is a gradient method and can therefore not be changed.

 

Assay and Related Substances data

Aripiprazole USP Monograph Methods

 

Suitability Requirements

Resolution:
NLT 2.0 between aripiprazole and aripiprazole related compound F

Tailing factor:
NMT 1.5 for aripiprazole

Relative retention time (RRT):
1.0 for aripiprazole and
1.1 for aripiprazole related compound F

Chromatogram

Chromatographic Data (System Suitability Solution)

Compound Retention Time (min) RRT Tailing Factor Resolution
Aripiprazole 12.0 1.0 1.4 -
Aripiprazole related compound F 12.5 1.05 1.3 2.8

Recommended Products

  • Acetic acid (glacial) 100% anhydrous for analysis—EMSURE® ACS, ISO, Reag. Ph. Eur. (CATALOGUE NUMBER 1.00063)
  • Acetonitrile (gradient grade for liquid chromatography)—LiChrosolv® Reag. Ph. Eur. (CATALOGUE NUMBER 1.00030)
  • Methanol (gradient grade for liquid chromatography)—LiChrosolv® Reag. Ph. Eur. (CATALOGUE NUMBER 1.06007)
  • Potassium bromide for IR spectroscopy—Uvasol® (CATALOGUE NUMBER 1.04907)
  • Purospher® STAR RP-18 endcapped (3 µm) 100 x 4.6 mm (CATALOGUE NUMBER 1.50469)
  • Trifluoroacetic acid for spectroscopy—Uvasol® (CATALOGUE NUMBER 1.08262)  
  • Water for chromatography (LC-MS grade)—LiChrosolv® (CATALOGUE NUMBER 1.15333) or fresh water from the Milli-Q® system
  • Aripiprazole United States Pharmacopeia (USP) Reference Standard (CATALOGUE NUMBER 1042634 USP)
  • Aripiprazole Related Compound F United States Pharmacopeia (USP) Reference Standard (CATALOGUE NUMBER 1042689 USP)

For more information, please download the compendium.

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