Abstract:
Provided is a liquid chromatograph system and method configured to accurately obtain measurements by minimizing deviations in measurements due to a transfer from one measurement method to another measurement method. An aspect of the system and method includes minimizing deviations in measurements when a measurement method from a measurement system of a liquid chromatograph is transferred to measurement system under high pressure and high velocity. Such a transfer includes deviations due to differences in analysis conditions. The present subject matter uses a dwell volume value so as to minimize a deviation of measurement result due to methods before and after transfer. Another aspect includes calculating a correction value when there is a deviation in the measurement result, and automatically reflecting the correction value for the method transfer.

Description:
CLAIM OF PRIORITY 
     The present application claims priority from Japanese Patent Application No. 2008-134904 filed on May 23, 2008, the content of which is hereby incorporated by reference into this application. 
     BACKGROUND OF THE INVENTION 
     1. Field of the Invention 
     The present invention relates to a way of method transfer of liquid chromatograph and a liquid chromatograph system. 
     2. Description of the Related Art 
     An analytic technology utilizing a liquid chromatograph system (herein below will be called as liquid chromatography is required to be highly accurate. 
     In order to obtain highly accurate data of liquid chromatograph, a transfer of method is enumerated. 
     The method implies the technical conditions set in an liquid chromatograph, when liquid chromatograph is measured and includes, for example, such as flow rate, injection amount and pressure limit. 
     Conventionally, as disclosed in Japanese patent document JP-A-2003-194795, a transfer of method was performed in such a manner that after correcting time axis, local data are caused to match with respect to a reference value having a same time scale or after transferring time axis, the data are caused to correspond to a reference value based on a different time scale. 
     However, a transfer of the method, when an analysis is performed under a condition where a linear velocity (which represents a velocity when a certain component passes through a column) is faster than a conventional one (for example, a linear velocity of a few times faster than a conventional velocity), has been performed according to know-how and the like based on experiences until now, and no considerations with regard to improving accuracy have been given particularly. 
     SUMMARY OF THE INVENTION 
     A feature of the present invention is to transfer a certain liquid chromatograph method (first method) to another method (second method) under a condition in which the linear velocity is faster than that in the first method. 
     Another aspect of the present invention is to use data of a column (for example, such as an inner diameter of the column, length of the column and diameter of particle) for the transfer of the method. 
     Still another aspect of the present invention is to use a dwell volume (a volume representing that of from the portion where eluent is mixed to a column inlet) for the transfer of the method in order to reduce a deviation of measurement results by the methods before and after the transfer. 
     Further aspect of the present invention is to calculate a correction value from measurement data for correcting the measurement result and to use the correction value for the transfer of the method. 
     Still further aspect of the present invention is to use at least one of a linear velocity (which represents a velocity when a certain component passes through a column) and a pressure (which represents a hydrostatic pressure applied at a pump outlet) of the method after transfer that is set in advance for the transfer of the method. 
     According to the present invention, a certain method of liquid chromatograph can be transferred in high accuracy to another method that is operated under a further high velocity condition. 
    
    
     
       BRIEF DESCRIPTION OF THE DRAWINGS 
         FIG. 1  is a system configuration diagram showing embodiment 1 of the present invention; 
         FIG. 2  is a flow line diagram of the system showing embodiment 1 of the present invention; 
         FIG. 3  is a operating panel for a method transfer showing embodiment 1 of the present invention; 
         FIG. 4  is a operating panel for a method transfer showing embodiment 1 of the present invention; 
         FIG. 5  is a measurement example before and after transfer for explaining embodiment 1 of the present invention; and 
         FIG. 6  is a flowchart of an operation according to embodiment 2 of the present invention. 
     
    
    
     DESCRIPTION OF THE PREFERRED EMBODIMENTS 
     At first, a way of method transfer will be explained and then a mode for performing the transfer in high accuracy will be explained. 
     Embodiment 1 
     Herein below, embodiment 1 of the present invention will be explained with reference to the drawings. 
       FIG. 1  shows a system configuration of the present invention. A liquid chromatograph device  1  is constituted by a pump  2 , an auto sampler  3 , a column oven  4 , a detector  5 , a data processing device  6 , a method transfer processing computer  7 , an input device  8  and an output device  9 . From the input device  8  parameters of a method that is an object for transfer are input from the input device  8  to the method transfer processing computer  7  and the method transfer is performed therein. At the time of analysis, commands calculated and set by the method transfer processing computer  7  are issued from the data processing device  6 , and a group of parameters are transmitted to the pump  2 , the auto sampler  3 , the column oven  4  and the detector  5 . Measured values of respective components detected by the detector  5  are fetched by the data processing device  6  and an analysis result is transmitted to the output device  9 . 
     Further, the function of the method transfer processing computer  7  can be incorporated into the data processing device  6 . 
       FIG. 2  shows an example of flow line configurations of the present invention applied to the gradient analysis. Eluent  10 A and  10 B are respectively sucked by pumps  11 A and  11 B and are transferred after mixed to a column oven  13  via an auto sampler  13 . A sample is injected from the auto sampler  13  and transferred to an column  15 . Respective solutes in the sample are separated and developed by the eluent (mobile phase)  10 A or  10 B in the column (stationary phase)  15 . Detention time of these solutes are different depending on separation ratio thereof existing in the mobile phase or the stationary phases. In order to stabilize the detention time of the respective solute, the column  15  is held in a constant temperature by utilizing the column oven  14 . The respective solutes separated and developed reach a cell  17  in a detector  13  while having differences with regard to the detention times and are wasted to a waste tank  18 . 
     Lists of parameters used for the measurement transfer are shown in Tables 1 and 2. Now, a calculation of method transfer will be explained. 
     
       
         
               
               
               
             
               
               
               
               
               
             
           
               
                   
                 TABLE 1 
               
             
             
               
                   
                   
               
               
                   
                 Input 
                   
               
             
          
           
               
                   
                   
                   
                 Ultra high-speed 
                   
               
               
                   
                   
                 liquid 
                 liquid 
               
               
                 No. 
                 Parameters 
                 chromatograph 
                 chromatograph 
                 Output 
               
               
                   
               
               
                 1 
                 Column inner 
                 D 0   
                 D 1   
                   
               
               
                   
                 diameter 
               
               
                 2 
                 Column length 
                 L 0   
                 L 1   
               
               
                 3 
                 Particle 
                 d 0   
                 d 1   
               
               
                   
                 diameter 
               
               
                 4 
                 Flow rate 
                 F 0   
                   
                 F 
               
               
                 5 
                 Injection 
                 V 0   
                   
                 V 
               
               
                   
                 amount 
               
               
                 6 
                 Pressure 
                 P 0   
                 P limit   
                 P 
               
               
                 7 
                 Linear velocity 
                   
                 f 
               
               
                 8 
                 Time program 
                 Table 2 
                   
                 Table 2 
               
               
                   
               
             
          
         
       
     
     
       
         
               
               
               
             
               
               
               
               
               
             
           
               
                   
                 TABLE 2 
               
             
             
               
                   
                   
               
               
                   
                 Input 
                   
               
             
          
           
               
                   
                   
                   
                 Ultra high-speed 
                   
               
               
                   
                   
                   
                 liquid 
               
               
                 No 
                 Parameters 
                 liquid chromatograph 
                 chromatograph 
                 Output 
               
               
                   
               
               
                 1 
                 Time 
                 T 0   
                   
                 T 
               
               
                 2 
                 % B 
                 B 0   
                   
                 B 
               
               
                   
               
             
          
         
       
     
     At first, when shifting an analysis method from a liquid chromatograph column to a ultra high-speed liquid chromatograph column, a flow rate is calculated so that a linear velocity of the ultra high-speed liquid chromatograph column becomes equal to that of the liquid chromatograph. Since even when column particle diameters are different, porosity is generally constant, and although the column length has a correlation with the pressure loss and the theoretical plate number, but has no direct correlation with the linear velocity. 
     Subsequently, a primary pressure value of the ultra high-speed liquid chromatograph column is calculated based on the column length, particle diameter and the pressure value of the liquid chromatograph column. Then, by using the pressure limit value (P limit  in Table 1) of the ultra high-speed liquid chromatograph as a target, the flow rate is pulled up. In the present invention, as the pressure limit value 80% of a set value is selected. For example, when 50 MPa is set for the pressure limit, the flow rate is pulled up to 40 MPa corresponding to 80% thereof as the target. 
     Subsequently, calculation of gradient time program is performed. In this invention, the term “gradient time program” means the control program of eluent mixing ratio as a function of time. When the linear velocity is constant, time required when the sample passes through the column is proportional to the column length, the gradient time program also assumes a proportional relationship with the column length. When the linear velocity is pulled up, the time for the gradient time program becomes to anti-proportional to the linear velocity. 
     Further, when a volume inside a column becomes small, since a delay of gradient elution cannot be neglected, a value of a dwell volume is incorporated in a calculation of time program. 
     Herein below, output items for the method transfer and equations for the calculation will be explained. 
     (1) Flow Rate F 
     The flow rate F in the method for the ultra high-speed liquid chromatograph is calculated from a product of a square of inner diameter ratio of the columns of the ultra high-speed liquid chromatograph and the liquid chromatograph and the flow rate of the method for the liquid chromatograph. This is shown in equation (1). 
     
       
         
           
             
               
                 
                   F 
                   = 
                   
                     
                       
                         F 
                         0 
                       
                       ⁡ 
                       
                         ( 
                         
                           
                             D 
                             1 
                           
                           
                             D 
                             0 
                           
                         
                         ) 
                       
                     
                     2 
                   
                 
               
               
                 
                   ( 
                   1 
                   ) 
                 
               
             
           
         
       
     
     Herein, F 0  is the flow rate in the method for the liquid chromatograph, D 0  is the column inner diameter for the liquid chromatograph and D 1  is the column inner diameter for the ultra high-speed liquid chromatograph. 
     Herein below, the equation (2) for calculation when the flow rate is pulled up while considering the pressure limit is shown below. 
                   F   =         (       D   1       D   0       )     2     ×     F   0     ×   f             (   2   )               
(2) Sample Injection Volume V
 
     The sample injection volume V in the method for the ultra high-speed liquid chromatograph is calculated from a product of a square of inner diameter ratio of the columns of the ultra high-speed liquid chromatograph and the liquid chromatograph and the sample injection volume of the method for the liquid chromatograph. This is shown in equation (3). 
     
       
         
           
             
               
                 
                   V 
                   = 
                   
                     
                       
                         ( 
                         
                           
                             D 
                             1 
                           
                           
                             D 
                             0 
                           
                         
                         ) 
                       
                       2 
                     
                     × 
                     
                       V 
                       0 
                     
                   
                 
               
               
                 
                   ( 
                   3 
                   ) 
                 
               
             
           
         
       
     
     Herein, V 0  shows the sample injection volume of the method for the liquid chromatograph, D 0  is the column inner diameter for the liquid chromatograph and D 1  is the column inner diameter for the ultra high-speed liquid chromatograph. 
     (3) Pressure P 
     The pressure P in the method for the ultra high-speed liquid chromatograph is calculated from a product of a square of inner diameter ratio of the columns of the ultra high-speed liquid chromatograph and the liquid chromatograph, a flow rate ratio thereof, a column length ratio thereof and a square of column particle diameter ratio thereof. This is shown in equation (4). 
     
       
         
           
             
               
                 
                   P 
                   = 
                   
                     
                       P 
                       0 
                     
                     × 
                     
                       
                         ( 
                         
                           
                             D 
                             0 
                           
                           
                             D 
                             1 
                           
                         
                         ) 
                       
                       2 
                     
                     × 
                     
                       
                         F 
                         1 
                       
                       
                         F 
                         0 
                       
                     
                     × 
                     
                       
                         L 
                         1 
                       
                       
                         L 
                         0 
                       
                     
                     × 
                     
                       
                         ( 
                         
                           
                             d 
                             0 
                           
                           
                             d 
                             1 
                           
                         
                         ) 
                       
                       2 
                     
                   
                 
               
               
                 
                   ( 
                   4 
                   ) 
                 
               
             
           
         
       
     
     Herein, P 0  is a pressure of the method for the liquid chromatograph, D 0  is the column inner diameter for the liquid chromatograph, D 1  is the column inner diameter for the ultra high-speed liquid chromatograph, F 0  is the flow rate for the liquid chromatograph, F 1  is the flow rate for the ultra high-speed liquid chromatograph, L 0  the column length for the liquid chromatograph, d 0  is the particle diameter for the liquid chromatograph and d 1  is the particle diameter for the ultra high-speed liquid chromatograph. 
     (4) Time Program T 
     First, the case wherein the pressure limit and the dwell volume are not considered will be explained in equation (5). The value of the time program is in a proportional relationship with the column length. 
     
       
         
           
             
               
                 
                   T 
                   = 
                   
                     
                       T 
                       0 
                     
                     ⁡ 
                     
                       ( 
                       
                         
                           L 
                           1 
                         
                         
                           L 
                           0 
                         
                       
                       ) 
                     
                   
                 
               
               
                 
                   ( 
                   5 
                   ) 
                 
               
             
           
         
       
     
     Next, the case when only the dwell volume is considered is shown in equation (6). 
     
       
         
           
             
               
                 
                   
                     ( 
                     
                       T 
                       + 
                       
                         T 
                         
                           delay 
                           ⁢ 
                           
                               
                           
                           ⁢ 
                           1 
                         
                       
                     
                     ) 
                   
                   = 
                   
                     
                       ( 
                       
                         
                           T 
                           0 
                         
                         + 
                         
                           T 
                           
                             delay 
                             ⁢ 
                             
                                 
                             
                             ⁢ 
                             0 
                           
                         
                       
                       ) 
                     
                     × 
                     
                       
                         L 
                         1 
                       
                       
                         L 
                         0 
                       
                     
                   
                 
               
               
                 
                   ( 
                   6 
                   ) 
                 
               
             
           
         
       
     
     Herein, T shows a time program for the ultra high-speed liquid chromatograph, T 0  is a time program for the liquid chromatograph, T delay0  is a dwell volume for the liquid chromatograph and T delay1  is a dwell volume for ultra high-speed liquid chromatograph. T delay0  is calculated according to the following equation (7). 
     
       
         
           
             
               
                 
                   
                     T 
                     
                       delay 
                       ⁢ 
                       
                           
                       
                       ⁢ 
                       0 
                     
                   
                   = 
                   
                     
                       
                         
                           
                             The 
                             ⁢ 
                             
                                 
                             
                             ⁢ 
                             volume 
                             ⁢ 
                             
                                 
                             
                             ⁢ 
                             of 
                             ⁢ 
                             
                                 
                             
                             ⁢ 
                             the 
                             ⁢ 
                             
                                 
                             
                             ⁢ 
                             mixer 
                           
                         
                       
                       
                         
                           
                             of 
                             ⁢ 
                             
                                 
                             
                             ⁢ 
                             the 
                             ⁢ 
                             
                                 
                             
                             ⁢ 
                             original 
                             ⁢ 
                             
                                 
                             
                             ⁢ 
                             method 
                             ⁢ 
                             
                                 
                             
                             ⁢ 
                             
                               ( 
                               µl 
                               ) 
                             
                           
                         
                       
                     
                     
                       
                         F 
                         0 
                       
                       × 
                       1000 
                     
                   
                 
               
               
                 
                   ( 
                   7 
                   ) 
                 
               
             
           
         
       
     
     In the equation (7), “The volume of the mixer of the original method” is a value of dwell volume for the liquid chromatograph. F 0  is the flow rate for the liquid chromatograph. T delay1  is calculated according to the following equation (8). 
     
       
         
           
             
               
                 
                   
                     T 
                     
                       delay 
                       ⁢ 
                       
                           
                       
                       ⁢ 
                       1 
                     
                   
                   = 
                   
                     
                       
                         
                           
                             The 
                             ⁢ 
                             
                                 
                             
                             ⁢ 
                             volume 
                             ⁢ 
                             
                                 
                             
                             ⁢ 
                             of 
                             ⁢ 
                             
                                 
                             
                             ⁢ 
                             the 
                             ⁢ 
                             
                                 
                             
                             ⁢ 
                             mixer 
                           
                         
                       
                       
                         
                           
                             of 
                             ⁢ 
                             
                                 
                             
                             ⁢ 
                             the 
                             ⁢ 
                             
                                 
                             
                             ⁢ 
                             new 
                             ⁢ 
                             
                                 
                             
                             ⁢ 
                             method 
                             ⁢ 
                             
                                 
                             
                             ⁢ 
                             
                               ( 
                               µl 
                               ) 
                             
                           
                         
                       
                     
                     
                       F 
                       × 
                       1000 
                     
                   
                 
               
               
                 
                   ( 
                   8 
                   ) 
                 
               
             
           
         
       
     
     In the equation (8), “The volume of the mixer of the new method” is a value of dwell volume for the ultra high-speed liquid chromatograph. F is a flow rate for the ultra high-speed liquid chromatograph. 
     Then, the case wherein only the pressure limit is considered will be explained. A value of the time program is proportional to the column length and is anti-proportional to the pulled up linear velocity. This is shown in equation (9). 
     
       
         
           
             
               
                 
                   T 
                   = 
                   
                     
                       T 
                       0 
                     
                     × 
                     
                       1 
                       f 
                     
                     × 
                     
                       ( 
                       
                         
                           L 
                           1 
                         
                         
                           L 
                           0 
                         
                       
                       ) 
                     
                   
                 
               
               
                 
                   ( 
                   9 
                   ) 
                 
               
             
           
         
       
     
     At last, the case wherein the pressure limit and the dwell volume are considered will be explained. The value of the time program is affected by the dwell volume as well as is anti-proportional to the pulled up linear velocity. The formula for the calculation when assumed the linear velocity as f is shown in equation (10). 
     
       
         
           
             
               
                 
                   
                     ( 
                     
                       T 
                       + 
                       
                         T 
                         
                           delay 
                           ⁢ 
                           
                               
                           
                           ⁢ 
                           1 
                         
                       
                     
                     ) 
                   
                   = 
                   
                     
                       ( 
                       
                         
                           T 
                           0 
                         
                         + 
                         
                           T 
                           
                             delay 
                             ⁢ 
                             
                                 
                             
                             ⁢ 
                             0 
                           
                         
                       
                       ) 
                     
                     × 
                     
                       1 
                       f 
                     
                     × 
                     
                       
                         L 
                         1 
                       
                       
                         L 
                         0 
                       
                     
                   
                 
               
               
                 
                   ( 
                   10 
                   ) 
                 
               
             
           
         
       
     
     The T delay0  and T delay1  are those shown in the previous equations. 
       FIGS. 3 and 4  show the operating panel representing a computer program tool used for the method transfer that automatically perform the above process (1)˜(4). The tool includes a form portion as shown in  FIG. 3  in which parameters such as a flow rate and an injection volume are input, and a sheet portion as shown in  FIG. 4  in which the gradient time program is input. 
     In the form portion as shown in  FIG. 3 , set values of the method before transfer are input in the corresponding dialog boxes such as a column inner diameter  19 , a column length  20 , a particle diameter  21 , a flow rate  22 , an injection volume  23  and a pressure  24 . The values of a column used in the measurement system after the transfer are set in the dialog boxes for a column diameter  25 , a column length  26  and a particle diameter  27 . A flow rate  28 , an injection amount  29  and a pressure  30  are also provided in these dialog boxes. 
     When the linear velocities before and after transfer are set equal, a radio button  31  for “linear velocity is constant” is selected. 
     When the linear velocity is pulled up while considering the pressure limit, a radio button  32  for “pressure limit is considered” is selected, and a limit value of the pressure is set at a pressure limit box  33 . A target linear velocity is pulled up to 80% of the value set at the pressure limit box  33 . 
     When directly designating a linear velocity multiplying factor, a radio button  35  for “linear velocity factor is set” is selected and the multiplying factor is set at a linear velocity factor box  34 . 
     When performing a correction with regard to the dwell volume, a check box  36  for “transfer considering mixer delay” is selected and a dwell volume in the measurement system before transfer is set at a original mixer volume box  37 . Further, a dwell volume in the measurement system after transfer is set at a new mixer volume box  38 . 
     Settings of time programs are performed at a sheet portion as shown in  FIG. 4 . A time program of the method before transfer is set at a reference Time Program Table  40 . 
     After completing the setting, when a transfer execution button  39  is pressed, a flow rate  28 , an injection volume  29  and a pressure  30  in the measurement system after transfer are calculated. Further, transferred values of time program are output at a new Time Program Table  41 . 
       FIG. 5  shows an example of measurement data (chromatogram) obtained by using methods before and after transfer. Columns having a same performance were used before and after transfer and the measurement was performed at 3 times higher velocity (linear velocity “3”). 
     The gradient corresponding to the peak in  FIG. 5  are as follows. 
     1: Acetanilide 
     2: Acetophenone 
     3: Propiophenone 
     4: Butirophenone 
     5: Benzophenone 
     6: Valerophenone 
     7: Hexanophenone 
     8: Heptanophenone 
     9: Octanophenone 
     A list of parameters of the method is shown in Table 3. Settings of gradient time program before transfer is shown in Table 4 and settings of gradient time program after transfer is shown in Table 5. Further, retention time ratio of respective peeks are shown in Table 6. 
     
       
         
               
               
               
               
             
               
               
               
               
             
           
               
                   
                 TABLE 3 
               
               
                   
                   
               
               
                   
                   
                 Method before 
                 Method after 
               
               
                   
                 Item to be set 
                 transfer 
                 transfer 
               
               
                   
                   
               
             
             
               
                   
               
             
          
           
               
                   
                 Column inner 
                 2 
                 2 
               
               
                   
                 diameter [mm] 
               
               
                   
                 Column length [mm] 
                 50 
                 50 
               
               
                   
                 Particle diameter 
                 2 
                 2 
               
               
                   
                 [mμ] 
               
               
                   
                 Flow rate [ml/min] 
                 0.2 
                 0.6 
               
               
                   
                 Injection volume 
                 2 
                 2 
               
               
                   
                 [μl] 
               
               
                   
                 Pressure [Mpa] 
                 9 
                 27 
               
               
                   
                 Linear velocity 
                   
                 3 
               
               
                   
                 Mixer volume [μl] 
                 700 
                 300 
               
               
                   
                   
               
             
          
         
       
     
     
       
         
               
               
               
             
               
               
               
             
           
               
                   
                 TABLE 4 
               
               
                   
                   
               
               
                   
                 Time 
                   
               
               
                   
                 [min] 
                 % B 
               
               
                   
                   
               
             
             
               
                   
               
             
          
           
               
                   
                 0.0 
                 65 
               
               
                   
                 5.0 
                 5 
               
               
                   
                 5.1 
                 65 
               
               
                   
                 8.0 
                 65 
               
               
                   
                   
               
             
          
         
       
     
     
       
         
               
               
               
             
               
               
               
             
           
               
                   
                 TABLE 5 
               
               
                   
                   
               
               
                   
                 Time 
                   
               
               
                   
                 [min] 
                 % B 
               
               
                   
                   
               
             
             
               
                   
               
             
          
           
               
                   
                 0.0 
                 65 
               
               
                   
                 1.7 
                 5 
               
               
                   
                 1.8 
                 65 
               
               
                   
                 3.0 
                 65 
               
               
                   
                   
               
             
          
         
       
     
     
       
         
               
               
               
             
           
               
                 TABLE 6 
               
               
                   
               
               
                   
                 Method before 
                 Method after 
               
               
                 Retention time ratio 
                 transfer 
                 transfer 
               
               
                   
               
             
             
               
                 t 2 /t 1   
                 2.02 
                 2.02 
               
               
                 t 3 /t 2   
                 1.42 
                 1.45 
               
               
                 t 4 /t 3   
                 1.21 
                 1.20 
               
               
                 t 5 /t 4   
                 1.06 
                 1.07 
               
               
                 t 6 /t 5   
                 1.08 
                 1.08 
               
               
                 t 7 /t 6   
                 1.11 
                 1.12 
               
               
                 t 8 /t 7   
                 1.09 
                 1.09 
               
               
                 t 9 /t 8   
                 1.08 
                 1.09 
               
               
                   
               
             
          
         
       
     
     The retention time ratio t 2 /t 1  shows a retention time ratio of No. 1 and No. 2 peeks. Under a same analysis condition, it is considered as desirable that an accuracy of retention time value in a measurement of a certain component is below 3%. Although since the measurement systems are different with regard to the methods before and after transfer in the present invention, it is not said that the measurement is performed under a same analysis condition, however, the above value is used as an index for an accuracy evaluation of the retention time. In the methods before and after transfer, since the accuracy of the retention time ratios between respective peeks are all below 3%, a good result is maintained. 
     Embodiment 2 
     As embodiment 2, an embodiment is shown wherein when the retention time ratios differ, the flow rate and the time for the gradient time program are shifted in order to correct the deviation. 
     A flowchart of an operation performed according to the present embodiment is shown in  FIG. 6 . 
     By the measurement with the method before transfer, the retention times of the measurement components become clear. When assuming a retention time of a certain component before transfer as tx and a retention time of the same component obtained by the method after transfer as ty, the flow rate is corrected as follows so as to match the retention times.
 
 F =( f×ty )÷ tx  
 
     Wherein, f shows a linear velocity. In association with this, the gradient time program is also shifted by the flow rate correction component from a formula for the calculation. 
     In Table 3, for example, an instance when the holding time ratio of No. 2 peek is matched will be considered. The holding time of No. 2 peek with the method before transfer is 2.65. That with the method after transfer is 0.85. Thereby, the value of the flow rate is corrected to 0.85×3/2.65 times. The values of the time program are respectively shifted by the flow rate correction component from the equation for the calculation of the time program. 
     Although the present invention is particularly advantageous for a transfer and optimization of method from a liquid chromatograph to a super high speed liquid chromatograph, but not limited to the above embodiments and can be modified other than the above within the spirit of the present invention. For example, through setting the linear velocity f to a value below 1 and setting the items such as column length and the particle diameter properly, a transfer from a method under a condition of a high velocity and a high pressure to a method under a general purpose condition can be effected.