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Team TFS

Magnesium Oxide Determination.jpg



Magnesium is the fourth most abundant cation in the human body and plays a key role in many physiological processes, including regulating nerve and muscle function and supporting energy production. To maintain adequate magnesium levels, many people take magnesium oxide (MgO) as a dietary supplement. MgO is also found in over-the-counter medications to treat headaches, constipation, and indigestion. However, consuming large doses of magnesium can cause harm. Therefore, to ensure pharmaceuticals and nutraceuticals contain the stated dose, precise and reproducible methods for assaying MgO in these products are essential.


Determination of magnesium oxide in pharmaceutical products


Several techniques are available for assaying MgO content in pharmaceutical products, including titrimetric and ion chromatography (IC) based methods. Until recently, the United States Pharmacopoeia (USP) monograph method for MgO assay in pharmaceuticals was based on titration. However, while effective and widely used, this method is less quantitative than modern instrumental methods and is subject to interferences, leading to inaccurate results.


Monograph modernization: Keeping pace with improvements in IC


The USP-NF seeks to ensure monographs reflect modern laboratory methods, and regularly revises outdated or less accurate techniques. As part of these modernization efforts, the USP proposed an IC method to replace the titration procedure used for the MgO assay. The same method also replaces a wet chemical method used for the Limit of Calcium test. This method was validated using a Thermo Scientific™ Dionex™ IonPac™ CS16 column, which incorporates a high-capacity, weak cation-exchange stationary phase functionalized with carboxylic acid groups, well suited for this application. The new method will ensure pharmaceutical manufacturers benefit from more accurate results.


Advanced IC columns: Putting the revised USP monograph method to the test


We recently evaluated the revised IC method for the MgO assay and Limit of Calcium test using a Dionex IonPac CS16 column and Thermo Scientific™ Dionex™ ICS-6000 HPIC™ system. Full details of the method are reported in this application note.


First, we assessed the performance of the setup against the revised monograph’s system suitability requirements. The resolution between the magnesium and calcium ion peaks for the system suitability standard solution must not be less than 3.0. A chromatogram showing the separation of the system suitability standard containing MgO and calcium carbonate is presented in Figure 1. The measured peak resolution was 5.04, meeting this requirement.


Additionally, the magnesium peak tailing factor for a 33 μg/mL standard solution of MgO must not be greater than 2.0, and the relative standard deviation (RSD) for replicate injections of the same standard solution must not be greater than 0.73%. Retention time, peak area, and peak height RSDs were determined for two separate Dionex IonPac CS16-5 mm columns from different lots. The retention times of the magnesium and calcium peaks on the two columns differed by 0.05% and 0.80% respectively, highlighting the reproducibility of this approach. Tailing factors were in close agreement and within the required limit for the two columns, and all RSDs were below the 0.73% threshold.


Method robustness was also assessed by examining how ±10% variations in flow rate, column temperature, and eluent concentration affected peak asymmetry, resolution, and retention times. These variations did not result in substantial changes, and the method was found to be suitable for the MgO assay.


An accurate and reliable method for determining MgO and calcium


Given the suitability and robustness of the system and monograph method, this approach was used to analyze two commercial MgO drug products (one tablet and one capsule formulation). According to the USP acceptance criteria, the tablets or capsules should contain between 90% and 110% of the labeled amount of MgO. Here, the samples were found to contain 106% and 104% of the labeled amount of MgO, both within the acceptable range stated in the monograph.


The accuracy of the method was also evaluated by measuring recoveries of magnesium and calcium at two concentrations. Recovery of the two spiked levels in both samples was within the acceptable range.


In the revised USP monograph for MgO, the atomic absorption procedure for the Limit of Calcium test is replaced by an IC procedure. Using the eluent conditions as reported in the revised method, the retention time for calcium was 11.26 mins, in good agreement with the retention time stated in the monograph. System suitability requirements for the Limit of Calcium test were the same as for the MgO assay, and were all met, underlining the reliability of the method.


Improving accuracy and reproducibility in pharmaceutical analysis


Ongoing advances in IC technology are pushing the limits of performance for this important analytical technique. The Dionex IonPac CS16 column used in the revised USP monograph method highlighted here is highly effective for the MgO assay and Limit of Calcium test, providing excellent separation, linearity, reproducibility, and sensitivity in accordance with, or better than, the method requirements.


Read more about this method for MgO determination here.

Figure 1. IC chromatogram of a system suitability standard (33 μg/mL of USP MgO and 5 μg/mL of USP calcium carbonate), obtained using a Thermo Scientific Dionex ICS-6000 HPIC system.Figure 1. IC chromatogram of a system suitability standard (33 μg/mL of USP MgO and 5 μg/mL of USP calcium carbonate), obtained using a Thermo Scientific Dionex ICS-6000 HPIC system.





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