Method and device for automatic peak integration

1 . A computer implemented method for automatic peak integration of at least one chromatogram of at least one sample, wherein the sample comprises at least one analyte and at least one chemical related substance, wherein the method comprises the following steps:

a) retrieving at least one chromatogram of the chemical related substance and at least one chromatogram of the analyte, wherein retrieving the at least one chromatogram comprises pretreating the sample by adding the chemical related substance at a predefined concentration that is higher than a concentration of the analyte and performing at least one chromatography run on the sample by a mass spectrometry device that includes a detector and a mass filter, wherein the mass spectrometry device is coupled to a liquid chromatography device configured to separate the analyte of the sample from other components of the sample for detection, and wherein the mass spectrometry device is coupled to the liquid chromatography device through an interface that includes an ionization source configured to generate molecular ions and transfer the molecular ions to a gas phase;

b) evaluating the chromatogram of the chemical related substance, wherein the evaluating comprises

b1) determining at least one initial value for analyte retention time by determining retention time of the chemical related substance, including determining a local intensity maximum within a predefined retention time interval based on a quantifier-to-qualifier ratio that is determined to be a characteristic quantifier-to-qualifier ratio of the analyte of the sample and one or both of adding the retention time of the chemical related substance with a pre-determined or pre-defined constant offset or multiplying the retention time of the chemical related substance with a pre-determined or pre-defined constant factor based on a retention time shift of the retention time of the chemical related substance,

b2) determining at least one initial value for analyte peak shape parameters by determining peak shape parameters of at least one peak of the chemical related substance chromatogram; and

c) evaluating the chromatogram of the analyte, wherein the evaluating comprises

c1) at least one position determining step, wherein the analyte retention time is determined by applying a tolerance interval based on the initial value of the retention time of the chemical related substance, and

c2) at least one peak integration step, wherein analyte peak area and analyte peak shape are determined by applying at least one fitting analysis to the chromatogram of the analyte by considering the initial value for analyte peak shape parameters and the analyte retention time.

2 . The method according to claim 1 , wherein the method steps a) to c) are performed fully automatic.

3 . The method according to claim 1 , wherein the determining of the retention time of the chemical related substance comprises determining of patterns of multiple local maxima within the predefined retention time interval, wherein the patterns have a predefined distance between the maxima.

4 . The method according to claim 3 , wherein the determining of the patterns of multiple local maxima is performed considering a predefined interval for the quantifier-to-qualifier ratio at the position of the maximum.

5 . The method according to claim 1 , wherein the initial value for analyte retention time is further determined by adjusting the predefined retention time interval according to the determined local maximum corrected by one or both of the pre-determined or pre-defined constant offset or the pre-determined or pre-defined constant factor.

6 . The method according to claim 1 , wherein the analyte retention time t is determined using the tolerance interval and the tolerance interval is determined from the chemical related substance chromatogram as domain, wherein the tolerance interval t±ε for analyte peak retention time t comprises an error interval of the analyte peak retention time ε, which is set to the respective error interval of peak retention time of the chemical related substance.

7 . The method according to claim 1 , wherein the determining of the at least one initial value for analyte peak shape parameters comprises fitting at least one peak of the chemical related substance chromatogram, wherein the fitting comprises using at least one curve fitting technique selected from polynomial interpolation, Gauss-Newton algorithm, and Fourier-Transformation.

8 . The method according to claim 1 , wherein the analyte retention time is determined by using at least one curve fitting technique, wherein the initial value for analyte retention time is used as start value for the curve fitting.

9 . The method according to claim 8 , wherein the curve fitting technique comprises using at least one fit selected from the group consisting of polynomial interpolation, Gauss-Newton algorithm, and Fourier-Transformation.

10 . The method according to claim 1 , wherein the tolerance interval is a first tolerance interval and the method comprises determining a second tolerance interval, wherein the second tolerance interval p±ε is given by the respective determined initial value p for analyte peak shape parameters and an error interval±ε.

11 . The method according to claim 10 , wherein the error interval of the analyte peak shape parameters±ε is set to the error interval of the peak shape parameters of the chemical related substance.

12 . The method according to claim 1 , wherein in the peak integration step the analyte chromatogram is fitted using at least one exponentially modified Gaussian function.

13 . The method according to claim 1 , wherein the evaluating one or both of the chromatogram of the chemical related substance or of the chromatogram of the analyte comprises at least one preprocessing step, wherein the preprocessing comprises one or more of: selecting at least one region of interest in the chromatogram; at least one smoothing step comprising applying one or more of a moving average filter, a Gaussian filter, a discrete wavelet denoising, a Savitzky-Golay smoothing, a Loess smoothing; at least one background subtraction step comprising one or more of an asymmetric weighted least squares fit with regularization, applying a morphological top hat filter, a discrete or continuous wavelet base background determination, and/or determining a moving average minima.

14 . The method of claim 1 , further comprising determining the predefined retention time interval based on a chromatographic noise level.

15 . The method of claim 14 , further comprising determining the predefined retention time interval based further on a determined level of chemical similarity of the chemical related substance and the analyte of the sample.

16 . A computer-implementable processing line for automatic peak integration of at least one chromatogram of at least one sample, wherein the sample comprises at least one analyte and at least one chemical related substance, and wherein the processing line comprises:

at least one data collector configured for retrieving at least one chromatogram of the chemical related substance and at least one chromatogram of the analyte; and

at least one evaluation device configured for evaluating the chromatogram of the chemical related substance and the chromatogram of the analyte;

wherein the evaluation device comprises at least one retention time hardware processor configured for determining at least one initial value for analyte retention time by determining retention time of the chemical related substance, including determining a local intensity maximum within a predefined retention time interval based on a quantifier-to-qualifier ratio that is determined to be a characteristic quantifier-to-qualifier ratio of the analyte of the sample,

wherein the evaluation device comprises one or both of at least one adder digital circuit configured for adding the retention time of the chemical related substance with a pre-determined or pre-defined constant offset or at least one multiplier digital circuit configured for multiplying the retention time of the chemical related substance with a pre-determined or pre-defined constant factor based on a retention time shift of the retention time of the chemical related substance,

wherein the evaluation device comprises at least one position determining device configured for determining the analyte retention time by applying a tolerance interval based on the initial value of the retention time of the chemical related substance,

wherein the evaluation device furthermore comprises at least one peak hardware processor configured for determining at least one initial value for analyte peak shape parameters by determining peak shape parameters of at least one peak of the chemical related substance chromatogram, and

wherein the evaluation device comprises at least one fitting device configured for determining analyte peak area and analyte peak shape by applying at least one fitting analysis to the chromatogram of the analyte by considering the initial value for analyte peak shape parameters and the analyte retention time,

wherein the processing line is integrated into a mass spectrometry device that is coupled to a liquid chromatography device configured to separate the analyte of the sample from other components of the sample for detection, and the mass spectrometry device is coupled to the liquid chromatography device through an interface that includes an ionization source configured to generate molecular ions and transfer the molecular ions to a gas phase.

17 . A mass spectrometry system comprising at least one mass spectrometry device comprising at least one mass filter and at least one detector; and at least one computer-implementable processing line according to claim 16 .