Analysis of Ibuprofen in Tablets According to the US Pharmacopoiea using a Varian 920-LC Analytical HPLC and Pursuit®XRs column

By Phuong TruongVarian Australia Pty Ltd

679 Springvale Rd Mulgrave VIC Australia

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Varian 920-LC

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Introduction

• Assays of active pharmaceutical ingredients (API) in medications are common in the pharmaceutical industry

• Often they are to quantitate the API and contaminants• Ibuprofen is a NSAID in widespread use around the world• 4-isobutylacetophenone (Ibuprofen related compound C) is a

breakdown product of Ibuprofen• It can adversely affect the central nervous system• The USP requires Ibuprofen related compound C to be

determined at < 0.1% per tablet• USP proscribe

• a 250 mm x 4.6 mm ID x 5 m L1 type (C18) column• Valerophenone internal standard

• In this work the recommended column was compared to a 100 x 4.6 x 3 m column

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Instrumentation

• Varian 920-LC Analytical HPLC (part no 00100xxx00)• Quaternary gradient pump with 4 channel degasser• 200 position autosampler with 100 L syringe• Thermostated column compartment• Diode Array detector

• Columns• Varian Pursuit®XRs columns feature 100Å silica, high

sample loadability, extended pH range, outstanding resolution and excellent column lifetime

– Varian Pursuit® XRs 100 x 4.6 mm x 3m column (part no AXXXX100X046)

– Varian Pursuit® XRs 250 x 4.6 mm x 5m column (part no AXXXX100X046)

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Instrumental Conditions

Mobile Phase 1% chloroacetic acid in water pH 3/Acetonitrile 40:60 v/v

Flow rate 2 ml/min

Wavelength 254 nm

Temperature Ambient

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Definitions – Resolution and Selectivity ()

'Bk

mAU

rt

mt 'Ak

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Chromatographic Resolution and Selectivity

• Resolution R is similar to selectivity but takes into account peak width

• Baseline resolution is when R=1.5

• Capacity factor • Selectivity

m

mrA t

ttk

'

BA

ArBr

WW

ttR

])()[(2'

Ak

'

'

B

A

k

k

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Standards - Pursuit®XRs 250 x 4.6 x 5m Column

• Ibuprofen and Internal Std with 250 mm x 5 m column

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Standards – Pursuit®XRs 250 x 4.6 x 5m Column

• Internal Std and Ibuprofen related compound C with 250 mm x 5 m column

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Results – Pursuit®XRs 250 x 4.6 x 5m

Resolution

(USP > 2.5)

Assymetry

(USP < 2.5)

Selectivity

Ibuprofen 1.29

I/S in Ibuprofen solution

7.3 1.00 1.29

I/S 1.06

Ibuprofen related C solution

5.1 1.01 1.18

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Standards – Pursuit®XRs 100 x 4.6 x 3m Column

• Ibuprofen and Internal Std with Pursuit® XRs 100 mm x 3 m column

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Standards –Pursuit®XRs 100 x 4.6 x 3m Column

• Internal Std and Ibuprofen related compound C with Pursuit® XRs 100 mm x 3 m column

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Results – Pursuit® XRs 100 x 4.6 x 3m

Resolution

(USP > 2.5)

Assymetry

(USP < 2.5)

Selectivity

Ibuprofen 1.27

I/S in Ibuprofen solution

5.3 1.01 1.29

I/S 1.13

Ibuprofen related C solution

4.0 1.10 1.18

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Ibuprofen Tablet

Chromatogram of Ibuprofen tablet sample spiked with I/S using a Pursuit® XRs 100 x 3m column

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Spectral Confirmation using PDA Detector

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Data for Ibuprofen Tablets

% of labelled Concentration of Ibuprofen

Assymetry of Ibuprofen

Assymetry of I/S

Resolution between Ibuprofen and Valerophenone I/S

101.9% 1.27 1.08 5.4

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Conclusion

• The Varian 920-LC and Pursuit® XRs 3m columns significantly improve throughput of an Ibuprofen assay compared to the USP recommended columns

• The calculated concentration of Ibuprofen in the tablet complies with USP requirements of nominal + 10%

• The sensitivity of 920-LC PDA detector ensures the LOD for the Ibuprofen related C compound is 10 fold lower than USP

• The PDA detector allowed positive confirmation the unknown peak in the tablet was Ibuprofen related compound C (4-isobutylacetophenone)