Detecting lithium ions in prescription drugs utilizing MALDI-TOF

Utilizing alkali-metal cation recognition of α-cyclodextrin to detect lithium ions by MALDI-TOF


Posted: 22 February 2023 | Ahmad Amini, Johan Carlsson |

Right here, Ahmad Amini and Johan Carlsson from the Swedish Medical Merchandise Company focus on using matrix‑assisted laser desorption/ionisation time-of-flight mass spectrometry (MALDI-TOF MS) for identification of lithium in pharmaceutical preparations.

Lithium (Li) is the third aspect within the periodic desk that belongs to the group of alkali metals. It was found by Johann August Arfwedson within the early 1800s within the mineral petalite. That is thought to elucidate the origin of the aspect’s identify; from lithos (Greek for stone). It’s discovered as completely different salts reminiscent of sulphate, acetate and chloride. Lithium has 9 recognized isotopes, of which two are secure – 6Li and 7Li, which have abundances of seven.5 % and 92.5 %, respectively.1

Lithium at excessive concentrations is poisonous to people, animals and crops, eg, ingestion of 5g of LiCl could cause deadly toxicity”

Lithium, relying on its focus or publicity, may very well be biologically necessary to dwelling organisms.2,3 Lithium at low-to-intermediate focus has been used as a therapeutic agent for greater than 50 years for the therapy of bipolar dysfunction.4 Nonetheless, lithium at excessive concentrations is poisonous to people, animals and crops, eg, ingestion of 5g of LiCl could cause deadly toxicity.5 Lithium has additionally demonstrated to be an efficient cathionising agent for MALDI-analysis of, eg, pure wax esters, sphingolipids, carbohydrates, lipids and polymers.6-8

Cyclodextrins are a household of cyclic oligomers produced from starch via enzymatic digestion.9 Essentially the most ample pure cyclodextrins are α-CD, β-CD and γ-CD, together with respectively six, seven and eight glucopyranose items. They current a form just like a hole torus with completely different polarities of their inside and exterior surfaces; ie, hydrophobic interior cavity and hydrophilic exterior.10

The inside of the cyclodextrins readily associates with varied natural molecules to kind inclusion complexes.10,11 The hydroxyl teams on the mouth of the CD cavity kind supramolecular complexes by hydrogen bonding or electrostatic interactions.12 Such properties allow the formation of host-guest complexation, with inorganic metallic salts.13,14 The driving forces behind the host-guest inclusion complexation of the CD and particular person visitor molecule embrace electrostatic, hydrogen bonding, van der Waals and hydrophobic interactions.15-17

Tender ionisation methods, reminiscent of MALDI-TOF MS and electrospray ionisation, have supplied the opportunity of exploring the noncovalent CD complexes.9,18,19

Within the current research adduct formation between α-CD and lithium ions has been exploited to detect lithium in prescription drugs.

Outcomes and dialogue

α-cyclodextrin, like different cyclodextrins reminiscent of β-CD, has a excessive affinity to pair with varied alkali metals within the pattern matrix to kind quite a lot of adducts. As illustrated in Determine 1 the constructive ion mode MALDI evaluation of α-CD and β-CD generate ion types of alkali metallic adducts, eg, [α-CD-Li]+, [α-CD-Na]+ and [α-CD-K]+. α-CD (MW = 792.8 g/mol), α-CD versus β-CD, has excessive aqueous solubility, ie, greater than 100 g per litre of water at 25oC. CD is a co-matrix and features as an alkali metallic sink capturing metallic ions, ie, Li+, Na+ and Okay+. That is because of the excessive affinity of sugars to kind alkali-metal ion adducts in mass spectrometry.20

Affiliation with the alkali metallic ions, and thereby formation of the cathionised CD, is dependent upon the affinity of the CD for these metallic ions, the CD/metallic ratio in addition to metallic cation properties reminiscent of ion radius and electron configuration.13

Subsequently, an answer of fifty mg/ml (51mM) α-CD in water was used as solvent to have an extra of α-CD molecules for the adduct formation.

Lithium, because of its smaller radius and excessive polarising energy, can exchange Na+ and Okay+ in α-CD.

Totally different lithium salts, ie, lithium sulphate, lithium chloride, lithium acetate and lithium trifluoro acetate, at completely different concentrations within the vary of 10-200 µg/ml dissolved in 50mM α-CD have been analysed. As Determine 2 illustrates the bottom focus that may very well be detected was lower than 0.3 µg/ml.

Lithium, because of its smaller radius and excessive polarising energy, can exchange Na+ and Okay+ in α-CD.22 The relative abundance ratio of 6Li+ and 7Li+ was decided to be 95.2 ± 1.0% (94-96 %) and 4.7% ± 1.0% (3-6 %) from the height areas (A) or peak intensities by the next formulation:

ALi (7 or 6) /(ALi (6) +ALi (7) )

The decided values deviate considerably from the reported isotopic ratios, ie, 92.5 % and seven.5= %.1,7 It could depend upon the competitors between 6Li and 7Li, current at a lot greater focus, to be ionised. As anticipated, the 6Li+ isotope is just not detected when lithium focus is near the restrict of detection (LOD). Determine 3 depicts spectrum from MALDI-TOF MS evaluation of lithium in a lithium pill.

Conclusions: MALDI-TOF MS evaluation of lithium

Alpha-cyclodextrin doped MALDI-TOF MS supplies a quick process for the identification of lithium in numerous analyte samples. The extent of LOD was discovered to be depending on the complexity of the pattern matrix, ie, the LOD will increase when pattern matrix was concerned. The isotopic abundance ratio of 7Li was decided to be 95% ± 1%.

Concerning the authors Ahmad Amini is a pharmaceutical assessor on the Swedish Medical Merchandise Company. He acquired his PhD in analytical pharmaceutical chemistry in 1998 at Uppsala College. Following post-doctoral research on proteomics at Purdue College, underneath supervision of Professor Fred E Regnier, Ahmad joined the SMPA laboratory in 2001. At the moment, he’s concerned in supervising graduate and undergraduate college students and methodology improvement for characterisation of monoclonal antibodies. Johan Carlsson is a laboratory assessor on the Swedish Medical Merchandise Company. He graduated from Stockholm College with a Grasp of Science with a minor in diet in 2010. The subsequent 12 months he labored as a service technician of laboratory devices. Johan’s PhD research on the College of Gothenburg have been targeted on meals and allergy, and the impact of fatty acids on immune cells. Following employment on the R&D division of a biotechnology firm in Uppsala he joined the SMPA in 2020. Centered primarily on peptides and proteins, widespread methods have been CE, gel electrophoresis and ELISA, in addition to MALDI targeted on small molecules. Disclaimer: The manuscript presents the private opinions of the authors and doesn’t essentially characterize the views or insurance policies of SMPA.