Alternatives to amino acid analysis for the purity control of pharmaceutical grade L‐alanine

Abstract

The quality control of drugs is important for safety of patients and consumers. International pharmacopoeias mostly employed HPLC with UV detection for this purpose. This is always a problem when the drugs, such as most amino acids, are lacking a chromophor. Instead of UV detection, the impurity control of alanine was performed using charged aerosol detector, evaporative light-scattering detector, nano quantity analyte detector, MS detector, and as an orthogonal method, quantitative NMR spectroscopy. The charged aerosol detector, MS detector, and quantitative NMR spectroscopy provided similar and precise results, whereas the evaporative light-scattering detector and nano quantity analyte detector revealed some problems regarding sensitivity, linearity, and robustness.

Quantitative NMR spectroscopy of biologically active substances and excipients

“…Owing to the widespread medical care of amino acids their quality control is of crucial importance. However, due to the absence of the essential chromophor required for an UV-detection in most of the amino acids, the determination of low level impurities is an analytical challenge [19,88]. Since amino acids are produced by various manufacturing processes, i.e.…”

“…In a comparative case study using L-alanine (Ala) as a representative amino acid a quantitative analysis of potential impurities was carried out using HPLC equipped with different evaporation based detectors and, as an orthogonal method, the non-separating technique 1 H qNMR spectroscopy [19]. The industrial scale production of Ala utilizes chemical and enzymatic synthesis as well as extraction of protein hydrolysates [90]; thereby, fumaric acid (FA), maleic acid (MA), aspartic acid (Asp), and glutamic acid (Glu) were identified as potential impurities in Ala. 1 H NMR spectroscopy yields at least one baseline separated signal for each impurity except for Asp.…”

“…Using qNMR spectroscopy it is sufficient to find, out of the multitude of NMR signals, a single baseline separated resonance for each component of interest. Besides the application of elaborative pulse sequences and line shape fitting techniques [7] an optimal separation of overlapping resonances can be achieved by changing the kind of solvent [8][9][10][11][12][13][14] or the pH value of the test solution [15][16][17][18][19], by applying different sample concentrations [20][21][22], or by adding auxiliary reagents such as cyclodextrins [23][24][25] or lanthanide shift reagents [23,26]. In some cases, the temperature also affects the signal separation [27,28].…”

Effects of Densities of Brominated Flame Retardants on the Detection Response for HPLC Analysis with a Corona-charged Aerosol Detector

“…[9][10] The universal response is a prominent feature that enables us to make quantitative analyses without having to prepare individual calibrations even for newly synthesized or unknown compounds. 1,10 From the comparison of these detectors, 9,[11][12][13] the reproducibility of the response from corona CAD is better than two other detectors. 14 The sensitivity of corona CAD is comparable to that of NQAD and better than that of ELSD.…”

Quantification of Triacylglycerol Molecular Species in Cocoa Butter Using High-Performance Liquid Chromatography Equipped with Nano Quantity Analyte Detector

“…The WCPC condenses water vapor onto the particles and increases their size so that they could be detected individually using a laser-based optical sensor. This detection method has a linear response to macrolides 27 , amino acids 28 , aromatic compounds 29 , vitamin E 29 , fatty acids 29 , etc. Therefore, we applied HPLC-NQAD to the quantification of TAG molecular species and confirmed the linearity of the calibration curves.…”