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

A7250

Sigma-Aldrich

N-Acetyl-L-cysteine, Sigma Grade, ≥99% (TLC), powder

A9165

Sigma-Aldrich

N-Acetyl-L-cysteine, BioReagent, suitable for cell culture

A8380

Sigma-Aldrich

5α-Androstan-17β-ol-3-one, ≥97.5%

A8199

Sigma-Aldrich

N-Acetyl-L-cysteine, BioXtra, ≥99% (TLC)

D2650

Sigma-Aldrich

Dimethyl sulfoxide, Hybri-Max^™, sterile-filtered, BioReagent, suitable for hybridoma, ≥99.7%

721964

Supelco

Methanol solution, NMR reference standard, 4% in methanol-d₄ (99.8 atom % D), NMR tube size 5 mm × 8 in.

PHR1098

Supelco

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

736201

Supelco

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

733466

Sigma-Aldrich

Acetonitrile, electronic grade, 99.999% trace metals basis

551384

Supelco

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

487031

Sigma-Aldrich

Sodium bicarbonate-¹²C, 99.9 atom % ¹²C

437557

Sigma-Aldrich

Acetonitrile, ≥99.5%, ACS reagent

10300

Sigma-Aldrich

5α-Androstan-17β-ol-3-one, purum, ≥99.0% (TLC)

276855

Sigma-Aldrich

Dimethyl sulfoxide, anhydrous, ≥99.9%

295426

Sigma-Aldrich

Hydrogen chloride, ReagentPlus^®, ≥99%

262552

Sigma-Aldrich

Potassium fluoride on Celite^®, extent of labeling: 50 wt. % loading, technical grade

278475

Sigma-Aldrich

2-Propanol, anhydrous, 99.5%

714690

Supelco

Ammonium formate solution, 10 mM in H₂O, suitable for HPLC

613339

Supelco

Formamide solution, NMR reference standard, 90% in DMSO-d₆ (99.9 atom % D), NMR tube size 3 mm × 8 in.

612707

Supelco

Formamide solution, NMR reference standard, 45% in DMSO-d₆ (99.9 atom % D), NMR tube size 3 mm × 8 in.

611891

Supelco

Formamide solution, NMR reference standard, 45% in DMSO-d₆ (99.9 atom % D), NMR tube size 5 mm × 8 in.

606723

Sigma-Aldrich

Methanol-¹²C, 99.95 atom % ¹²C

31573

Supelco

5α-Androstan-17β-ol-3-one, VETRANAL^®, analytical standard

437522

Sigma-Aldrich

2-Propanol, ACS reagent, ≥99.5%

673439

Sigma-Aldrich

Dimethyl sulfoxide solution, 50 wt. % in H₂O

PHR1072

Supelco

2-Propanol, Pharmaceutical Secondary Standard; Certified Reference Material

41640

Sigma-Aldrich

Dimethyl sulfoxide, puriss. p.a., ACS reagent, ≥99.9% (GC)

60004

Sigma-Aldrich

Acetonitrile, ≥99.5% (GC)

11625

Sigma-Aldrich

Sodium tetraborate decahydrate, puriss., meets analytical specification of Ph. Eur., BP, NF, 99.0-103.0%

673773

Sigma-Aldrich

2-Propanol, ACS reagent, ≥99.5%