# US 12,222,334 B2 · Use of low-bind surface coatings for analysis of tyrosine kinase inhibitors

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- Number: US 12,222,334 B2
- Document ID: US12222334B2
- Status: Granted
- Kind: B2
- Application number: 17/730,271
- Filed: 2022-04-27
- Published: 2022-10-27
- Granted: 2025-02-11
- Earliest claimed: 2021-04-27
- Assignees: Micromass UK Limited
- Applicants: Micromass UK Limited
- Inventors: Stephen Balloch; Lisa Jane Calton; Gareth Hammond
- Web page: https://patentgrep.com/patent/US12222334B2

## CPC

- G01N 30/16: Injection (G01N30/24 takes precedence)
- G01N 30/88: Integrated analysis systems specially adapted therefor, not covered by a single one of the groups G01N30/04 - G01N30/86
- G01N 30/7233: {interfaced to liquid or supercritical fluid chromatograph (interfaces in general for introducing or extracting samples to be analysed with specially adapted mass spectrometer, see H01J49/04)}
- G01N 33/94: involving narcotics {or drugs or pharmaceuticals, neurotransmitters or associated receptors}
- G01N 30/72: Mass spectrometers {(mass spectrometers per se H01J49/00)}
- G01N 2030/027: {Liquid chromatography}
- G01N 2030/524: {structural properties}
- 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)

## Abstract

The present disclosure discusses a method of separating a sample of tyrosine kinase inhibitors or metabolites of tyrosine kinase inhibitors which includes injecting the sample into the chromatographic system having one or more low-bind coated surfaces along the flow path; flowing the sample through the chromatographic system; separating the sample; and analyzing the separated sample. Consequently, the sample does not bind to the low-binding surface coatings (e.g., alkylsilyl coatings) of the flow path. The applied coating can reduce peak tailing and decrease carryover for tyrosine kinase inhibitor samples during chromatographic analysis.

## Claims

### Claim 1

A method of separating and analyzing tyrosine kinase inhibitors, the method comprising:
injecting a sample comprising one or more tyrosine kinase inhibitors into a chromatographic system, wherein the sample is prepared from plasma or serum obtained from a subject, and wherein the chromatographic system comprises a metallic flow path, wherein at least a portion of the metallic flow path is coated with a low-bind surface coating;
flowing the sample through the chromatographic system;
separating the one or more tyrosine kinase inhibitors from other components in the plasma or serum; and
passing the separated tyrosine kinase inhibitors to a detector.

### Claim 2 (depends on 1)

The method of claim 1, wherein the method further comprises analyzing the separated tyrosine kinase inhibitors to determine an identity and/or amount of tyrosine kinase inhibitors present in the plasma or serum.

### Claim 3 (depends on 1)

The method of claim 1, wherein the sample comprises two or more tyrosine kinase inhibitors, and wherein the method further comprises separating the two or more tyrosine kinase inhibitors from each other and determining an identity and/or amount of each separated tyrosine kinase inhibitor.

### Claim 4 (depends on 1)

The method according to claim 1, wherein the one or more tyrosine kinase inhibitors comprise at least one of imatinib, norimatinib (N-desmethyl imatinib), dasatinib, and nilotinib.

### Claim 5 (depends on 1)

The method according to claim 1, wherein the metallic flow path of the chromatographic system comprises interior wetted surfaces of a sample injector, a pre-column heater coupled to the sample injector and a chromatography column coupled to the pre-column heater, wherein injecting the sample comprises drawing the sample into the chromatographic system through a sample needle of the sample injector and passing the sample through the pre-column heater before the sample enters the chromatography column.

### Claim 6 (depends on 5)

The method according to claim 5, wherein the portion of the metallic flow path coated with the low-bind surface coating comprises the interior wetted surfaces of the sample needle.

### Claim 7 (depends on 5)

The method according to claim 5, wherein the portion of the metallic flow path coated with the low-bind surface coating comprises the interior wetted surfaces of a needle port of the sample injector.

### Claim 8 (depends on 5)

The method according to claim 5, wherein the portion of the metallic flow path coated with the low-bind surface coating comprises the interior wetted surfaces of the pre-column heater.

### Claim 9 (depends on 5)

The method according to claim 5, wherein the portion of the metallic flow path coated with the low-bind surface coating comprises the interior wetted surfaces of: a needle port, the sample needle, and the pre-column heater.

### Claim 10 (depends on 1)

The method according to claim 1, wherein the low-bind surface coating comprises an alky-silyl coating.

### Claim 11 (depends on 10)

The method according to claim 10, wherein the alkylsilyl coating comprises bis(trimethoxysilyl)ethane or bis(tirchlorosilyl)ethane.

### Claim 12 (depends on 10)

The method according to claim 10, wherein the alky-silyl coating comprises a first alkylsilyl coating layer in contact with the portion of the metallic flow path and a second alkylsilyl coating layer formed on the first alkylsilyl coating layer.

### Claim 13 (depends on 12)

The method according to claim 12, wherein the first coating layer comprises bis(trimethoxysilyl)ethane or bis(tirchlorosilyl)ethane, and wherein the second coating layer comprises n-decyltrichlorosilane.

### Claim 14 (depends on 1)

The method of claim 1, wherein the detector is a mass spectrometer.