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Agilent in Pharmaceutical Analysis, Issue 26 

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Agilent in Pharmaceutical Analysis

Issue 26 | March 2009

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What technologies from Agilent address melamine contamination in dairy products?

By Rong An
Agilent LC Senior Application Engineer

Melamine is a nitrogen-rich chemical that was illegally added to raw milk to boost apparent protein content, causing serious health problems. To monitor melamine levels in food matrices, government labs in China developed three analysis methods (the China GB methods). These methods incorporate a variety of technologies, including solid phase extraction (SPE), various LC equipment and columns, triple quadrupole LC/MS, and GC/MS. Despite the diversity of these technologies, Agilent offers complete solutions to successfully meet requirements of the Chinese National Standards, as well as United States Food and Drug Administration (FDA) guidelines.

Solid phase extraction (SPE) to clean up and concentrate trace melamine

Agilent SampliQ SCX SPE cartridges have been successfully used in sample preparation of milk and milk-derived products, as required in China GB/T 22388-2008. This cartridge contains sulfonic acid-modified divinyl benzene polymer with a mixed-mode retention mechanism (cation exchange and reverse phase), and it retains both basic and neutral compounds. By using a simple SPE protocol, Agilent SampliQ SCX cartridges (3 mL/60 mg) selectively extract the basic melamine with excellent recovery and remove milk matrix interferences, which improves data quality. SampliQ SCX cartridges can clean up milk or milk-derived ingredients and make them amenable to further LC, LC/MS or GC/MS analysis.

LC system for routine quantitation

HPLC with ultraviolet (UV) detection is a simple, popular, and affordable solution for routine quantitation of melamine. There are two LC methods based on two different separation mechanisms. One is a reverse phase method in ion-pair mode, while the other is an ion-exchange method.

Figure 1. The ZORBAX 300SCX column delivers excellent separation of melamine in raw milk after only protein precipitation. (Click here to see this image larger.)

The Agilent 1200 Series LC system with an Agilent ZORBAX SB-C8 column is a good choice for routine analysis of melamine in dairy products by reverse phase LC. [1] Optimized separation conditions produce good resolution between melamine and matrix interferences.

An Agilent ZORBAX 300SCX column is also an excellent column for melamine analysis when using a cation-exchange method. [1] Phosphate or ammonium acetate buffer can be used as the mobile phase. The latter is also used for LC/MS analysis of melamine with good selectivity of separation. The ion-exchange method is simpler and faster than the reverse phase method, but currently is validated only for limited matrices – raw milk (Figure 1) and liquid milk without additives.

Figure 2. Rapid separation of melamine standard and positive yogurt sample by RRLC after SPE. (Click here to see this image larger.)

LC system for high throughput analyses

Agilent 1200 Series Rapid Resolution LC (RRLC) systems, equipped with second-generation Agilent ZORBAX Rapid Resolution High Throughput (RRHT) columns with 1.8 µm particle size, deliver significantly faster results and higher data quality than conventional LC. RRLC is a most effective tool for method development and optimization, and for high-throughput fast LC analyses (Figure 2). A short RRHT column (4.6 x 50 mm, 1.8 µm) and RRLC instrumentation increase the speed of melamine analysis five- to six-fold without losing resolution. [1]

Triple quadrupole LC/MS for screening, confirmation, and quantitation

The Agilent 6410 Triple Quadrupole LC/MS system is one of the most sensitive and selective tools for trace amounts of melamine in complex food matrices. You can choose either a hydrophilic interaction chromatography (HILIC) column (Agilent ZORBAX Rx-SIL) or an Agilent ZORBAX 300SCX column for separation. The HILIC column is suitable for simultaneous determination of melamine and its derivatives, such as cyanuric acid, ammeline, and ammelide, and the ion-exchange column is referenced by a China GB method for the analysis of melamine in dairy products.

By using the Agilent 6410 Triple Quadrupole LC/MS system and ZORBAX columns, it is easy to obtain reproducible results with excellent sensitivity. [2] The LOQ for the 6410 is well below the requirement in China GB/T 22388-2008 (0.01 mg/kg) and the FDA method (0.25 µg/g).

GC/MS and GC/MS/MS with reduced analysis time

For melamine analysis in infant formula, GC/MS is a more popular tool than LC/MS/MS. GC/MS is also used for analysis of melamine and related compounds after derivatization. SIM/Scan on the Agilent 5975C Series GC/MSD can be used for simultaneous confirmation and quantitation, and the backflush function helps reduce run time dramatically. [3] In addition, the Agilent 7000A Triple Quadrupole GC/MS system will enable high-throughput analyses of complex samples with sensitivity and selectivity.

Total solution for melamine analysis

From sample preparation to analysis, Agilent offers complete solutions to successfully analyze melamine in dairy products or dairy-containing products. These include:

For specifics on analysis conditions and results, download the Agilent Application Notes listed below.

References

  1. “Quantitative Liquid Chromatography Analysis of Melamine in Dairy Products Using Agilent's 1120 Compact LC and 1200 Rapid Resolution LC,” Agilent publication number 5989-9949EN, 2008.
  2. “Rapid Screening and Confirmation of Melamine Residues in Milk and Its Products by Liquid Chromatography Tandem Mass Spectrometry,” Agilent publication number 5989-9950EN, 2008.
  3. “Rapid Screening of Melamine and Cyanuric Acid in Milk Products Using Agilent J&W HP-5ms GC Column and Agilent 7890A/5975C GC/MSD with Column Backflushing,” Agilent publication number 5989-9866EN, 2008.
 
 
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