# US 2023/0408461 A1 · Lc/ms adduct mitigation by vapor deposition coated surfaces

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- Number: US 2023/0408461 A1
- Document ID: US20230408461A1
- Status: Published application
- Kind: A1
- Application number: 18/216,064
- Filed: 2023-06-29
- Published: 2023-12-21
- Earliest claimed: 2020-01-31
- Assignees: Waters Technologies Corporation
- Applicants: Waters Technologies Corporation
- Inventors: Kerri M. Smith; Paul Rainville
- Web page: https://patentgrep.com/patent/US20230408461A1

## CPC

- G01N 30/56: Packing methods or coating methods
- G01N 30/72: Mass spectrometers {(mass spectrometers per se H01J49/00)}
- C23C 14/046: {Coating cavities or hollow spaces, e.g. interior of tubes; Infiltration of porous substrates}
- C23C 14/12: Organic material
- G01N 2030/027: {Liquid chromatography}
- G01N 2030/567: {coating}
- G01N 2030/8831: {involving peptides or proteins}
- G01N: INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES (measuring or testing apparatus or processes other than immunoassay, involving enzymes or microorganisms C12M, C12Q)
- C23C: COATING METALLIC MATERIAL; COATING MATERIAL WITH METALLIC MATERIAL; SURFACE TREATMENT OF METALLIC MATERIAL BY DIFFUSION INTO THE SURFACE, BY CHEMICAL CONVERSION OR SUBSTITUTION; COATING BY VACUUM EVAPORATION, BY SPUTTERING, BY ION IMPLANTATION OR BY CHEMICAL VAPOUR DEPOSITION, IN GENERAL (making metal-coated products by extrusion B21C23/22; covering with metal by connecting pre-existing layers to articles, see the relevant places, e.g. B21D39/00, B23K; metallising of glass C03C; metallising mortars, concrete, artificial stone, ceramics or natural stone C04B41/00; enamelling of, or applying a vitreous layer to, metals C23D; treating metal surfaces or coating of metals by electrolysis or electrophoresis C25D; single-crystal film growth C30B; by metallising textiles D06M11/83; decorating textiles by locally metallising D06Q1/04)

## Abstract

The present disclosure discusses a method of separating a sample (e.g., small organic acid metabolite) including coating a flow path of a chromatographic system. The coating along the flow path is vapor deposited and prevents or severely decreases metal interactions between the metallic chromatographic system and the sample.

## Claims

### Claim at position 1

1-20. (canceled)

### Claim 21

A method of separating and analyzing critical pairs in a sample comprising:
injecting the sample into a chromatographic system having a fluid-contacting coating on a metallic surface defining a sample flow path, wherein the coating comprises an alkylsilyl coating made using vapors of bis(trichlorosilyl)ethane or bis(trimethoxysilyl)ethane, and the sample comprises two or more structural isomers defining the critical pairs;
flowing the injected sample through the chromatographic system along the sample flow path;
separating the flowing sample with the chromatographic system; and
analyzing separated critical pairs with a mass spectrometer.

### Claim 22 (depends on 21)

The method of claim 21, wherein the separated critical pairs consist of isocitric acid and citric acid.

### Claim 23 (depends on 21)

The method of claim 21, wherein the separated critical pairs consist of methylmalonic acid and succinic acid.

### Claim 24 (depends on 21)

The method of claim 21, wherein the separated critical pairs consist of itaconic acid, 2-hydroxyglutaric acid, and cis-aconitic acid.

### Claim 25 (depends on 21)

The method of claim 21, wherein the separated critical pairs consist of malic acid and fumaric acid.

### Claim 26 (depends on 21)

The method of claim 21, wherein separating the sample comprises using a mixed mode anion exchange chromatographic method.

### Claim 27 (depends on 26)

The method of claim 26, wherein using a mixed mode anion exchange chromatographic method comprises using a phenyl-hexyl chromatographic column.

### Claim 28 (depends on 21)

The method of claim 21, wherein the metallic surface comprises column walls and frit surfaces.

### Claim 29 (depends on 22)

The method of claim 22, wherein resolution at 10% height of the separated critical pairs is increased over 20% as compared to a separation on a non-coated, standard chromatographic system.

### Claim 30 (depends on 21)

The method of claim 21, wherein peak areas of individual separated critical pairs increased from 1.2× to 4.2× as compared to separations on a non-coated, standard chromatographic system.