Evaluation of enantiomeric purity of magnesium-L-aspartate dihydrate.

Evaluation of enantiomeric purity of magnesium-L-aspartate dihydrate.

Journal of pharmaceutical and biomedical analysis (2014-09-30)

Oliver Wahl, Ulrike Holzgrabe

ABSTRACT

Magnesium supplementation in form of organic magnesium salts is a very popular practice. We examined the enantiomeric purity of "Magnesium aspartate dihydrate" monographed in the European Pharmacopeia. A chiral capillary zone electrophoresis using (2-hydroxypropyl)-β-cyclodextrin coupled to laser induced fluorescence detection and a HPLC-fluorescence method with chiral derivatization using o-phthaldialdehyde and N-acetyl-L-cysteine as an orthogonal method were developed and validated. Two batch samples of this substance and three drug products containing the salt were analyzed by means of both methods. The concentration of the D-enantiomer of aspartic acid ranged from 0.03 to 0.12%. Simulations of the synthesis revealed that the d-aspartic acid content is elevated if the dissolution of L-aspartic acid was performed at acidic pH values.

MATERIALS

Product Number

Brand

Product Description

I9030

Sigma-Aldrich

Isopropyl alcohol, meets USP testing specifications

110086

Sigma-Aldrich

Acetonitrile, ReagentPlus^®, 99%

S9640

Sigma-Aldrich

Sodium tetraborate decahydrate, ACS reagent, ≥99.5%

190764

Sigma-Aldrich

2-Propanol, ACS reagent, ≥99.5%

109827

Sigma-Aldrich

2-Propanol, Laboratory Reagent, ≥99.5%

494445

Sigma-Aldrich

Acetonitrile, biotech. grade, ≥99.93%

360457

Sigma-Aldrich

Acetonitrile, ACS reagent, ≥99.5%

59300

Sigma-Aldrich

2-Propanol, puriss. p.a., ACS reagent, ≥99.8% (GC)

L010300

Sigma-Aldrich

Ultrapure Acetonitrile

B9876

Sigma-Aldrich

Sodium tetraborate decahydrate, ReagentPlus^®, ≥99.5%

733466

Sigma-Aldrich

Acetonitrile, electronic grade, 99.999% trace metals basis

733784

Sigma-Aldrich

Formamide solution, NMR reference standard, 90% in DMSO-d₆ (99.9 atom % D), NMR tube size 10 mm × 8 in.

736201

Supelco

Formamide solution, NMR reference standard, 90% in DMSO-d₆ (99.9 atom % D), NMR tube size 5 mm × 8 in.

1601340

USP

Residual Solvent Class 2 - Acetonitrile, United States Pharmacopeia (USP) Reference Standard

1570428

USP

2-Propanol, United States Pharmacopeia (USP) Reference Standard

PHR1551

Supelco

Acetonitrile, Pharmaceutical Secondary Standard; Certified Reference Material

1005706

USP

Glacial acetic acid, United States Pharmacopeia (USP) Reference Standard

PHR1072

Supelco

2-Propanol, Pharmaceutical Secondary Standard; Certified Reference Material

PHR1107

Supelco

L-Glutamic acid, Pharmaceutical Secondary Standard; Certified Reference Material

95436

Supelco

L-Glutamic acid, certified reference material, TraceCERT^®, Manufactured by: Sigma-Aldrich Production GmbH, Switzerland

M0088000

Magnesium aspartate dihydrate, European Pharmacopoeia (EP) Reference Standard

PHR1098

Supelco

N-Acetyl-L-cysteine, Pharmaceutical Secondary Standard; Certified Reference Material

34851

Sigma-Aldrich

Acetonitrile, suitable for HPLC, gradient grade, ≥99.9%

650447

Sigma-Aldrich

2-Propanol, HPLC Plus, for HPLC, GC, and residue analysis, 99.9%

439134

Sigma-Aldrich

Acetonitrile, suitable for HPLC, gradient grade, ≥99.9%

34998

Sigma-Aldrich

Acetonitrile, HPLC Plus, ≥99.9%

31457

Sigma-Aldrich

Sodium tetraborate decahydrate, puriss. p.a., ACS reagent, reag. ISO, buffer substance, ≥99.5%

34442

Sigma-Aldrich

Acetonitrile, suitable for DNA synthesis, ≥99.9% (GC)

34863

Sigma-Aldrich

2-Propanol, suitable for HPLC, 99.9%

45983

Supelco

Acetonitrile, analytical standard