Olmesartan Medoxomil Identification and Assay by HPLC

Olmesartan Medoxomil USP Monograph Methods

Olmesartan medoxomil is an angiotensin II receptor antagonist that is used to treat high blood pressure. Furthermore, it is an ester prodrug that is completely and rapidly hydrolyzed into the active acid form, olmesartan. Olmesartan medoxomil was developed by Daiichi Sankyo in 1995.

Common commercial brand names:
Benicar (U.S.); Olmetec (E.U., Canada, and Japan); and WinBP, Olsar, and Golme (India)

In 2010, sales were $2.5 billion globally; the patent expired in 2016.

olmesartan medoxomil

In this compilation, we 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 were 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.

In this compilation, we have used the USP 40–NF 35 experimental conditions for olmesartan medoxomil in the following areas:

  • Identification — FTIR
  • Assay — HPLC and UHPLC (isocratic methods)
  • Related Substances — HPLC (gradient method)
  • Water Determination — Karl Fischer

The assay and reference standards methods were carried out with HPLC using RP-8 and RP-18 endcapped columns. In addition, the assay method was scaled to two shorter column dimensions with different particle sizes (3 and 2 µm particles).

We also included a new proposal for UHPLC analysis of olmesartan medoxomil related substances using LC-MS conditions (in-house method) and a proposal for heavy metal analysis (using ICP-OES or ICP-MS analysis) per suggestions in the new USP General Chapters 232 and 233, which will become active in 2018.

 

Identification

DEFINITION

Olmesartan medoxomil contains not less than (NLT) 98.5% and not more than (NMT) 101.5% of C29H30N6O6, calculated on the anhydrous and solvent-free basis.

Assay and Related Substances data

Purospher® STAR RP-18 Endcapped (5 µm)

Column: Purospher® STAR RP-18 endcapped (5 µm) 150 x 4.6 mm (Catalog No. 1.51455)

Injection: 10 µL

Detection UV 250 nm

Cell: 11 µL

Flow rate: 1 mL/min

Solution A: 15 mM monobasic potassium phosphate (pH = 3.4)

Solution B: Acetonitrile—gradient grade (Catalog No. 1.00030)

Mobile phase: Buffer and acetonitrile (33:17 v/v)

Temperature: 40 °C

Diluent 1: Acetonitrile and water (4:1)

Diluent 2: Acetonitrile and water (2:3)

Standard solution: 0.05 mg/mL of USP Olmesartan Medoxomil RS of the Standard Stock solution and 0.025 mg/mL of p-hydroxybenzoic acid isobutyl ester from the Internal standard solution in Diluent 2

Standard stock solution: 1 mg/mL of USP Olmesartan Medoxomil RS in Diluent 1

Internal standard solution: 0.5 mg/mL of p-hydroxybenzoic acid isobutyl ester in Diluent 2

Pressure drop: 63 Bar (907 psi)


Suitability Requirements

Resolution: NLT 4 between olmesartan medoxomil and p-hydroxybenzoic acid isobutyl ester

Materials

     
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