Analysis of Ibuprofen in Tablets According to the US Pharmacopoiea using a Varian 920-LC Analytical...
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Transcript of Analysis of Ibuprofen in Tablets According to the US Pharmacopoiea using a Varian 920-LC Analytical...
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)