	US 12,488,971 B2
	Computer implemented method for calibrating a customer mass spectrometry instrument for quantifier-qualifier-ratio check
Daniel Intelmann, München Süd (DE)
Assigned to Roche Diagnostics Operations, Inc., Indianapolis, IN (US)
Filed by Roche Diagnostics Operations, Inc., Indianapolis, IN (US)
Filed on Nov. 22, 2022, as Appl. No. 17/992,510.
Application 17/992,510 is a continuation of application No. PCT/EP2021/063820, filed on May 25, 2021.
Claims priority of application No. 20176542 (EP), filed on May 26, 2020.
Prior Publication US 2023/0079433 A1, Mar. 16, 2023
Int. Cl. H01J 49/00 (2006.01); G01N 33/68 (2006.01)

CPC H01J 49/0009 (2013.01)

9 Claims

1. A computer-implemented method for calibrating a customer mass spectrometry instrument for quantifier-qualifier-ratio check, the method comprising:

a) performing at least one manufacturer-site standardization, wherein a set of samples of a subject and a set of calibrator samples are measured in multiple replicates on a plurality of mass spectrometry instruments which constitute multiple measurements, wherein each measurement comprises multiple reaction monitoring with quantifier and qualifier transition for analyte and internal standard, wherein at least three adjustment factors are determined from the measurements of the set of samples of a subject and the set of calibrator samples,

wherein a first adjustment factor α depends on a difference between analyte and internal standard, wherein the first adjustment factor α is determined by α=R_mean,AQN/AQL/R_mean,IQN/IQL, wherein R_mean,AQN/AQLis a mean of the analyte quantifier-qualifier-ratios of the multiple measurements of step a) and R_mean,IQN/IQLis a mean of the internal standard quantifier-qualifier-ratios of the multiple measurements of step a),

wherein a second adjustment factor β depends on a difference between samples of a subject and calibrator samples for analyte quantifier-qualifier-ratio, wherein the second adjustment factor β is determined by β=R_{mean,patient,AQN/AQL}/R_{mean,calibrate,AQN/AQL}, wherein R_{mean,patient,AQN/AQL}is a mean of the analyte quantifier-qualifier-ratios of the multiple measurements of the samples of a subject of step a) and R_{mean,calibrator,AQN/AQL}is a mean of analyte quantifier-qualifier-ratios of the multiple measurements of the calibrator samples of step a), and

wherein a third adjustment factor γ depends on a difference between samples of a subject and calibrator samples for the internal standard quantifier-qualifier-ratio, wherein the third adjustment factor γ is determined by γ=R_{mean,patient,IQN/IQL}/R_{mean,calibrator,IQN/IQL}, wherein R_{mean,patient,IQN/IQL}is a mean of the internal standard quantifier-qualifier-ratios of the multiple measurements of the samples of a subject of step a) and R_{mean,calibrator,IQN/IQL}is a mean of internal standard quantifier-qualifier-ratios of the multiple measurements of the calibrator samples of step a),

b) performing at least one transfer step in which the adjustment factors are electronically transferred to a customer mass spectrometry instrument, and

c) performing at least one customer-site calibration, wherein the customer-site calibration comprises at least one calibration measurement, wherein a set of calibrator samples is measured on the customer mass spectrometry instrument and quantifier-qualifier-ratios are determined therefrom, wherein target values for quantifier-qualifier-ratios for analyte and for internal standard are set by applying the adjustment factors on the determined quantifier-qualifier-ratios, wherein the target value for the quantifier-qualifier-ratio R for analyte quantifier AQN and analyte qualifier AQL is set by

with R being a quantifier-qualifier peak area ratio of a single measurement, IQN being an internal standard quantifier, IQL being an internal standard qualifier, and N being a total number of quantifier-qualifier-ratios used for calculation, wherein the target value for a quantifier-qualifier-ratio R for internal standard quantifier ION and internal standard qualifier IQL is set by

with R being a quantifier-qualifier peak area ratio of a single measurement, AQN being an analyte quantifier, AQL being an analyte qualifier, and N being a total number of quantifier-qualifier-ratios used for calculation.