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Detection of quality deviations in paracetamol products

Fusion of Mass Spectrometry and Raman Spectroscopy Data

Ricardo Cunha

01 August, 2024

Source: vignettes/articles/demo_paracetamol.Rmd
demo_paracetamol.Rmd



Pre-processing

MS

Overview of MS analyses and respective analysis replicate groups and blanks.
analysis replicate blank description
20240415_Paracetamol_4152024_Paracetamol-Coffein-Aspirin_20240415-39-1_091 ass_1 blank Aspirin standard
20240415_Paracetamol_4152024_Paracetamol-Coffein-Aspirin_20240415-39-1_092 ass_1 blank Aspirin standard
20240415_Paracetamol_4152024_Paracetamol-Coffein-Aspirin_20240415-39-1_093 ass_1 blank Aspirin standard
20240415_Paracetamol_4152024_Paracetamol-Coffein-Aspirin_20240415-39-2_094 ass_2 blank Aspirin standard
20240415_Paracetamol_4152024_Paracetamol-Coffein-Aspirin_20240415-39-2_095 ass_2 blank Aspirin standard
20240415_Paracetamol_4152024_Paracetamol-Coffein-Aspirin_20240415-39-2_096 ass_2 blank Aspirin standard
20240415_Paracetamol_4152024_Paracetamol-Coffein-Aspirin_20240415-39-3_097 ass_3 blank Aspirin standard
20240415_Paracetamol_4152024_Paracetamol-Coffein-Aspirin_20240415-39-3_098 ass_3 blank Aspirin standard
20240415_Paracetamol_4152024_Paracetamol-Coffein-Aspirin_20240415-39-3_099 ass_3 blank Aspirin standard
20240415_Paracetamol_4152024_Paracetamol-Coffein-Aspirin_Blank_100 blank blank Reference background
20240415_Paracetamol_4152024_Paracetamol-Coffein-Aspirin_Blank_101 blank blank Reference background
20240415_Paracetamol_4152024_Paracetamol-Coffein-Aspirin_Blank_111 blank blank Reference background
20240415_Paracetamol_4152024_Paracetamol-Coffein-Aspirin_Blank_112 blank blank Reference background
20240516_Paracetamol_5162024_Paracetamol-Coffein-Aspirin_Blank_009 blank_e blank_e Reference background
20240516_Paracetamol_5162024_Paracetamol-Coffein-Aspirin_Blank_010 blank_e blank_e Reference background
20240516_Paracetamol_5162024_Paracetamol-Coffein-Aspirin_Blank_020 blank_e blank_e Reference background
20240516_Paracetamol_5162024_Paracetamol-Coffein-Aspirin_Blank_021 blank_e blank_e Reference background
20240516_Paracetamol_5162024_Paracetamol-Coffein-Aspirin_Blank_031 blank_e blank_e Reference background
20240516_Paracetamol_5162024_Paracetamol-Coffein-Aspirin_Blank_032 blank_e blank_e Reference background
20240516_Paracetamol_5162024_Paracetamol-Coffein-Aspirin_Blank_042 blank_e blank_e Reference background
20240516_Paracetamol_5162024_Paracetamol-Coffein-Aspirin_Blank_043 blank_e blank_e Reference background
20240516_Paracetamol_5162024_Paracetamol-Coffein-Aspirin_Blank_053 blank_e blank_e Reference background
20240516_Paracetamol_5162024_Paracetamol-Coffein-Aspirin_Blank_054 blank_e blank_e Reference background
20240415_Paracetamol_4152024_Paracetamol-Coffein-Aspirin_20240415-40-1_102 caff_1 blank Caffeine standard
20240415_Paracetamol_4152024_Paracetamol-Coffein-Aspirin_20240415-40-1_103 caff_1 blank Caffeine standard
20240415_Paracetamol_4152024_Paracetamol-Coffein-Aspirin_20240415-40-1_104 caff_1 blank Caffeine standard
20240415_Paracetamol_4152024_Paracetamol-Coffein-Aspirin_20240415-40-2_105 caff_2 blank Caffeine standard
20240415_Paracetamol_4152024_Paracetamol-Coffein-Aspirin_20240415-40-2_106 caff_2 blank Caffeine standard
20240415_Paracetamol_4152024_Paracetamol-Coffein-Aspirin_20240415-40-2_107 caff_2 blank Caffeine standard
20240415_Paracetamol_4152024_Paracetamol-Coffein-Aspirin_20240415-40-3_108 caff_3 blank Caffeine standard
20240415_Paracetamol_4152024_Paracetamol-Coffein-Aspirin_20240415-40-3_109 caff_3 blank Caffeine standard
20240415_Paracetamol_4152024_Paracetamol-Coffein-Aspirin_20240415-40-3_110 caff_3 blank Caffeine standard
20240415-31-1_003 fiz_a1 blank Paracetamol product
20240415-31-1_004 fiz_a1 blank Paracetamol product
20240415-31-1_005 fiz_a1 blank Paracetamol product
20240415-31-2_006 fiz_a2 blank Paracetamol product
20240415-31-2_007 fiz_a2 blank Paracetamol product
20240415-31-2_008 fiz_a2 blank Paracetamol product
20240415-31-3_009 fiz_a3 blank Paracetamol product
20240415-31-3_010 fiz_a3 blank Paracetamol product
20240415-31-3_011 fiz_a3 blank Paracetamol product
20240415-37-1_069 fiz_acid1 blank Paracetamol with acetic acid
20240415-37-1_070 fiz_acid1 blank Paracetamol with acetic acid
20240415-37-1_071 fiz_acid1 blank Paracetamol with acetic acid
20240415-37-2_072 fiz_acid2 blank Paracetamol with acetic acid
20240415-37-2_073 fiz_acid2 blank Paracetamol with acetic acid
20240415-37-2_074 fiz_acid2 blank Paracetamol with acetic acid
20240415-37-3_075 fiz_acid3 blank Paracetamol with acetic acid
20240415-37-3_076 fiz_acid3 blank Paracetamol with acetic acid
20240415-37-3_077 fiz_acid3 blank Paracetamol with acetic acid
20240415-35-1_047 fiz_ass1 blank Paracetamol with aspirin
20240415-35-1_048 fiz_ass1 blank Paracetamol with aspirin
20240415-35-1_049 fiz_ass1 blank Paracetamol with aspirin
20240415-35-2_050 fiz_ass2 blank Paracetamol with aspirin
20240415-35-2_051 fiz_ass2 blank Paracetamol with aspirin
20240415-35-2_052 fiz_ass2 blank Paracetamol with aspirin
20240415-35-3_053 fiz_ass3 blank Paracetamol with aspirin
20240415-35-3_054 fiz_ass3 blank Paracetamol with aspirin
20240415-35-3_055 fiz_ass3 blank Paracetamol with aspirin
20240415-32-1_014 fiz_b1 blank Paracetamol product
20240415-32-1_015 fiz_b1 blank Paracetamol product
20240415-32-1_016 fiz_b1 blank Paracetamol product
20240415-32-2_017 fiz_b2 blank Paracetamol product
20240415-32-2_018 fiz_b2 blank Paracetamol product
20240415-32-2_019 fiz_b2 blank Paracetamol product
20240415-32-3_020 fiz_b3 blank Paracetamol product
20240415-32-3_021 fiz_b3 blank Paracetamol product
20240415-32-3_022 fiz_b3 blank Paracetamol product
20240415-33-1_025 fiz_c1 blank Paracetamol product
20240415-33-1_026 fiz_c1 blank Paracetamol product
20240415-33-1_027 fiz_c1 blank Paracetamol product
20240415-33-2_028 fiz_c2 blank Paracetamol product
20240415-33-2_029 fiz_c2 blank Paracetamol product
20240415-33-2_030 fiz_c2 blank Paracetamol product
20240415-33-3_031 fiz_c3 blank Paracetamol product
20240415-33-3_032 fiz_c3 blank Paracetamol product
20240415-33-3_033 fiz_c3 blank Paracetamol product
20240415-34-1_036 fiz_caff1 blank Paracetamol with caffeine
20240415-34-1_037 fiz_caff1 blank Paracetamol with caffeine
20240415-34-1_038 fiz_caff1 blank Paracetamol with caffeine
20240415-34-2_039 fiz_caff2 blank Paracetamol with caffeine
20240415-34-2_040 fiz_caff2 blank Paracetamol with caffeine
20240415-34-2_041 fiz_caff2 blank Paracetamol with caffeine
20240415-34-3_042 fiz_caff3 blank Paracetamol with caffeine
20240415-34-3_043 fiz_caff3 blank Paracetamol with caffeine
20240415-34-3_044 fiz_caff3 blank Paracetamol with caffeine
20240415-36-1_058 fiz_d1 blank Paracetamol product
20240415-36-1_059 fiz_d1 blank Paracetamol product
20240415-36-1_060 fiz_d1 blank Paracetamol product
20240415-36-2_061 fiz_d2 blank Paracetamol product
20240415-36-2_062 fiz_d2 blank Paracetamol product
20240415-36-2_063 fiz_d2 blank Paracetamol product
20240415-36-3_064 fiz_d3 blank Paracetamol product
20240415-36-3_065 fiz_d3 blank Paracetamol product
20240415-36-3_066 fiz_d3 blank Paracetamol product
20240516_Paracetamol_5162024_Paracetamol-Coffein-Aspirin_12-1-1-1_011 fiz_e01 blank_e Paracetamol product
20240516_Paracetamol_5162024_Paracetamol-Coffein-Aspirin_12-1-1-2_012 fiz_e01 blank_e Paracetamol product
20240516_Paracetamol_5162024_Paracetamol-Coffein-Aspirin_12-1-1-3_013 fiz_e01 blank_e Paracetamol product
20240516_Paracetamol_5162024_Paracetamol-Coffein-Aspirin_12-1-2-1_014 fiz_e02 blank_e Paracetamol product
20240516_Paracetamol_5162024_Paracetamol-Coffein-Aspirin_12-1-2-2_015 fiz_e02 blank_e Paracetamol product
20240516_Paracetamol_5162024_Paracetamol-Coffein-Aspirin_12-1-2-3_016 fiz_e02 blank_e Paracetamol product
20240516_Paracetamol_5162024_Paracetamol-Coffein-Aspirin_12-1-3-1_017 fiz_e03 blank_e Paracetamol product
20240516_Paracetamol_5162024_Paracetamol-Coffein-Aspirin_12-1-3-2_018 fiz_e03 blank_e Paracetamol product
20240516_Paracetamol_5162024_Paracetamol-Coffein-Aspirin_12-1-3-3_019 fiz_e03 blank_e Paracetamol product
20240516_Paracetamol_5162024_Paracetamol-Coffein-Aspirin_12-2-1-1_022 fiz_e04 blank_e Paracetamol product
20240516_Paracetamol_5162024_Paracetamol-Coffein-Aspirin_12-2-1-2_023 fiz_e04 blank_e Paracetamol product
20240516_Paracetamol_5162024_Paracetamol-Coffein-Aspirin_12-2-1-3_024 fiz_e04 blank_e Paracetamol product
20240516_Paracetamol_5162024_Paracetamol-Coffein-Aspirin_12-2-2-1_025 fiz_e05 blank_e Paracetamol product
20240516_Paracetamol_5162024_Paracetamol-Coffein-Aspirin_12-2-2-2_026 fiz_e05 blank_e Paracetamol product
20240516_Paracetamol_5162024_Paracetamol-Coffein-Aspirin_12-2-2-3_027 fiz_e05 blank_e Paracetamol product
20240516_Paracetamol_5162024_Paracetamol-Coffein-Aspirin_12-2-3-1_028 fiz_e06 blank_e Paracetamol product
20240516_Paracetamol_5162024_Paracetamol-Coffein-Aspirin_12-2-3-2_029 fiz_e06 blank_e Paracetamol product
20240516_Paracetamol_5162024_Paracetamol-Coffein-Aspirin_12-2-3-3_030 fiz_e06 blank_e Paracetamol product
20240516_Paracetamol_5162024_Paracetamol-Coffein-Aspirin_12-3-1-1_033 fiz_e07 blank_e Paracetamol product
20240516_Paracetamol_5162024_Paracetamol-Coffein-Aspirin_12-3-1-2_034 fiz_e07 blank_e Paracetamol product
20240516_Paracetamol_5162024_Paracetamol-Coffein-Aspirin_12-3-1-3_035 fiz_e07 blank_e Paracetamol product
20240516_Paracetamol_5162024_Paracetamol-Coffein-Aspirin_12-3-2-1_036 fiz_e08 blank_e Paracetamol product
20240516_Paracetamol_5162024_Paracetamol-Coffein-Aspirin_12-3-2-2_037 fiz_e08 blank_e Paracetamol product
20240516_Paracetamol_5162024_Paracetamol-Coffein-Aspirin_12-3-2-3_038 fiz_e08 blank_e Paracetamol product
20240516_Paracetamol_5162024_Paracetamol-Coffein-Aspirin_12-3-3-1_039 fiz_e09 blank_e Paracetamol product
20240516_Paracetamol_5162024_Paracetamol-Coffein-Aspirin_12-3-3-2_040 fiz_e09 blank_e Paracetamol product
20240516_Paracetamol_5162024_Paracetamol-Coffein-Aspirin_12-3-3-3_041 fiz_e09 blank_e Paracetamol product
20240516_Paracetamol_5162024_Paracetamol-Coffein-Aspirin_12-4-1-1_044 fiz_e10 blank_e Paracetamol product
20240516_Paracetamol_5162024_Paracetamol-Coffein-Aspirin_12-4-1-2_045 fiz_e10 blank_e Paracetamol product
20240516_Paracetamol_5162024_Paracetamol-Coffein-Aspirin_12-4-1-3_046 fiz_e10 blank_e Paracetamol product
20240516_Paracetamol_5162024_Paracetamol-Coffein-Aspirin_12-4-2-1_047 fiz_e11 blank_e Paracetamol product
20240516_Paracetamol_5162024_Paracetamol-Coffein-Aspirin_12-4-2-2_048 fiz_e11 blank_e Paracetamol product
20240516_Paracetamol_5162024_Paracetamol-Coffein-Aspirin_12-4-3-1_050 fiz_e11 blank_e Paracetamol product
20240516_Paracetamol_5162024_Paracetamol-Coffein-Aspirin_12-4-3-2_051 fiz_e12 blank_e Paracetamol product
20240516_Paracetamol_5162024_Paracetamol-Coffein-Aspirin_12-4-3-3_052 fiz_e12 blank_e Paracetamol product
20240516_Paracetamol_5162024_Paracetamol-Coffein-Aspirin_12-42-3_049 fiz_e12 blank_e Paracetamol product
20240415_Paracetamol_4152024_Paracetamol-Coffein-Aspirin_20240415-41-1_113 par_1 blank Paracetamol standard
20240415_Paracetamol_4152024_Paracetamol-Coffein-Aspirin_20240415-41-1_114 par_1 blank Paracetamol standard
20240415_Paracetamol_4152024_Paracetamol-Coffein-Aspirin_20240415-41-1_115 par_1 blank Paracetamol standard
20240415_Paracetamol_4152024_Paracetamol-Coffein-Aspirin_20240415-41-2_116 par_2 blank Paracetamol standard
20240415_Paracetamol_4152024_Paracetamol-Coffein-Aspirin_20240415-41-2_117 par_2 blank Paracetamol standard
20240415_Paracetamol_4152024_Paracetamol-Coffein-Aspirin_20240415-41-2_118 par_2 blank Paracetamol standard
20240415_Paracetamol_4152024_Paracetamol-Coffein-Aspirin_20240415-41-3_119 par_3 blank Paracetamol standard
20240415_Paracetamol_4152024_Paracetamol-Coffein-Aspirin_20240415-41-3_120 par_3 blank Paracetamol standard
20240415_Paracetamol_4152024_Paracetamol-Coffein-Aspirin_20240415-41-3_121 par_3 blank Paracetamol standard 


ms_workflow_settings <- list(
  MassSpecSettings_BinSpectra_StreamFind(bins = list("rt" = 5, "mz" = 2), refBinAnalysis = 1),
  MassSpecSettings_NormalizeSpectra_minmax(),
  MassSpecSettings_AverageSpectra_StreamFind(),
  MassSpecSettings_SubtractBlankSpectra_StreamFind(negativeToZero = TRUE),
  MassSpecSettings_NormalizeSpectra_blockweight()
)

ms$add_settings(ms_workflow_settings)

ms$print_workflow()

Workflow
 1: BinSpectra (StreamFind)
 2: NormalizeSpectra (minmax)
 3: AverageSpectra (StreamFind)
 4: SubtractBlankSpectra (StreamFind)
 5: NormalizeSpectra (blockweight)
ms$run_workflow()
ms$plot_spectra()

Pre-processed spectra for each analysis. Retention time dimension in he created bins is collapsed for each mass-to-charge ratio 

ms$get_spectra()[1:10, ]
    analysis replicate polarity    rt    mz    intensity   bins     blank
      <char>    <char>    <int> <num> <num>        <num> <char>     <num>
 1:    ass_1     ass_1        1     0    56 7.223730e-04   0-56 0.4806362
 2:    ass_1     ass_1        1     5    56 0.000000e+00   5-56 0.2783423
 3:    ass_1     ass_1        1    10    56 8.938603e-04  10-56 0.2396827
 4:    ass_1     ass_1        1    15    56 7.981044e-04  15-56 0.4825239
 5:    ass_1     ass_1        1    20    56 5.882682e-04  20-56 0.5144360
 6:    ass_1     ass_1        1    25    56 7.743778e-04  25-56 0.6433077
 7:    ass_1     ass_1        1    30    56 4.271764e-04  30-56 0.9462764
 8:    ass_1     ass_1        1    35    56 0.000000e+00  35-56 0.8639968
 9:    ass_1     ass_1        1    40    56 0.000000e+00  40-56 0.5787367
10:    ass_1     ass_1        1    45    56 3.947558e-05  45-56 0.5303741

Raman

Overview of MS analyses and respective analysis replicate groups and blanks.
analysis replicate blank description
240411_1mgmLASS_200mW_OD3_2s_36n_pos1_r1 ass_1 blank Aspirin standard
240411_1mgmLASS_200mW_OD3_2s_36n_pos1_r2 ass_1 blank Aspirin standard
240411_1mgmLASS_200mW_OD3_2s_36n_pos1_r3 ass_1 blank Aspirin standard
240411_1mgmLASS_200mW_OD3_2s_36n_pos2_r1 ass_2 blank Aspirin standard
240411_1mgmLASS_200mW_OD3_2s_36n_pos2_r2 ass_2 blank Aspirin standard
240411_1mgmLASS_200mW_OD3_2s_36n_pos2_r3 ass_2 blank Aspirin standard
240411_1mgmLASS_200mW_OD3_2s_36n_pos3_r1 ass_3 blank Aspirin standard
240411_1mgmLASS_200mW_OD3_2s_36n_pos3_r2 ass_3 blank Aspirin standard
240411_1mgmLASS_200mW_OD3_2s_36n_pos3_r3 ass_3 blank Aspirin standard
240411_blank_200mW_OD3_2s_36n_pos1_r1 blank blank Reference background
240411_blank_200mW_OD3_2s_36n_pos1_r2 blank blank Reference background
240411_blank_200mW_OD3_2s_36n_pos1_r3 blank blank Reference background
240411_blank_200mW_OD3_2s_36n_pos2_r1 blank blank Reference background
240411_blank_200mW_OD3_2s_36n_pos2_r2 blank blank Reference background
240411_blank_200mW_OD3_2s_36n_pos2_r3 blank blank Reference background
240411_blank_200mW_OD3_2s_36n_pos3_r1 blank blank Reference background
240411_blank_200mW_OD3_2s_36n_pos3_r2 blank blank Reference background
240411_blank_200mW_OD3_2s_36n_pos3_r3 blank blank Reference background
240412_BlankH2O_200mW_OD3_2s_36n_pos1_r1 blank_e blank_e Reference background
240412_BlankH2O_200mW_OD3_2s_36n_pos1_r2 blank_e blank_e Reference background
240412_BlankH2O_200mW_OD3_2s_36n_pos1_r3 blank_e blank_e Reference background
240412_BlankH2O_200mW_OD3_2s_36n_pos2_r1 blank_e blank_e Reference background
240412_BlankH2O_200mW_OD3_2s_36n_pos2_r2 blank_e blank_e Reference background
240412_BlankH2O_200mW_OD3_2s_36n_pos2_r3 blank_e blank_e Reference background
240412_BlankH2O_200mW_OD3_2s_36n_pos3_r1 blank_e blank_e Reference background
240412_BlankH2O_200mW_OD3_2s_36n_pos3_r2 blank_e blank_e Reference background
240412_BlankH2O_200mW_OD3_2s_36n_pos3_r3 blank_e blank_e Reference background
240411_1mgmLCoffein_200mW_OD3_2s_36n_pos1_r1 caff_1 blank Caffeine standard
240411_1mgmLCoffein_200mW_OD3_2s_36n_pos1_r2 caff_1 blank Caffeine standard
240411_1mgmLCoffein_200mW_OD3_2s_36n_pos1_r3 caff_1 blank Caffeine standard
240411_1mgmLCoffein_200mW_OD3_2s_36n_pos2_r1 caff_2 blank Caffeine standard
240411_1mgmLCoffein_200mW_OD3_2s_36n_pos2_r2 caff_2 blank Caffeine standard
240411_1mgmLCoffein_200mW_OD3_2s_36n_pos2_r3 caff_2 blank Caffeine standard
240411_1mgmLCoffein_200mW_OD3_2s_36n_pos3_r1 caff_3 blank Caffeine standard
240411_1mgmLCoffein_200mW_OD3_2s_36n_pos3_r2 caff_3 blank Caffeine standard
240411_1mgmLCoffein_200mW_OD3_2s_36n_pos3_r3 caff_3 blank Caffeine standard
240411_Fizamol-11gealtert_200mW_OD3_2s_36n_pos1_r1 fiz_a1 blank Paracetamol product
240411_Fizamol-11gealtert_200mW_OD3_2s_36n_pos1_r2 fiz_a1 blank Paracetamol product
240411_Fizamol-11gealtert_200mW_OD3_2s_36n_pos1_r3 fiz_a1 blank Paracetamol product
240411_Fizamol-11gealtert_200mW_OD3_2s_36n_pos2_r1 fiz_a2 blank Paracetamol product
240411_Fizamol-11gealtert_200mW_OD3_2s_36n_pos2_r2 fiz_a2 blank Paracetamol product
240411_Fizamol-11gealtert_200mW_OD3_2s_36n_pos2_r3 fiz_a2 blank Paracetamol product
240411_Fizamol-11gealtert_200mW_OD3_2s_36n_pos3_r1 fiz_a3 blank Paracetamol product
240411_Fizamol-11gealtert_200mW_OD3_2s_36n_pos3_r2 fiz_a3 blank Paracetamol product
240411_Fizamol-11gealtert_200mW_OD3_2s_36n_pos3_r3 fiz_a3 blank Paracetamol product
240412_Fizamol-11+2prozentEssig_200mW_OD3_2s_36n_pos1_r1 fiz_acid1 blank Paracetamol with acetic acid
240412_Fizamol-11+2prozentEssig_200mW_OD3_2s_36n_pos1_r2 fiz_acid1 blank Paracetamol with acetic acid
240412_Fizamol-11+2prozentEssig_200mW_OD3_2s_36n_pos1_r3 fiz_acid1 blank Paracetamol with acetic acid
240412_Fizamol-11+2prozentEssig_200mW_OD3_2s_36n_pos2_r1 fiz_acid2 blank Paracetamol with acetic acid
240412_Fizamol-11+2prozentEssig_200mW_OD3_2s_36n_pos2_r2 fiz_acid2 blank Paracetamol with acetic acid
240412_Fizamol-11+2prozentEssig_200mW_OD3_2s_36n_pos2_r3 fiz_acid2 blank Paracetamol with acetic acid
240412_Fizamol-11+2prozentEssig_200mW_OD3_2s_36n_pos3_r1 fiz_acid3 blank Paracetamol with acetic acid
240412_Fizamol-11+2prozentEssig_200mW_OD3_2s_36n_pos3_r2 fiz_acid3 blank Paracetamol with acetic acid
240412_Fizamol-11+2prozentEssig_200mW_OD3_2s_36n_pos3_r3 fiz_acid3 blank Paracetamol with acetic acid
240411_Fizamol-11+1mgmLASS2_200mW_OD3_2s_36n_pos1_r1 fiz_ass1 blank Paracetamol with aspirin
240411_Fizamol-11+1mgmLASS2_200mW_OD3_2s_36n_pos1_r2 fiz_ass1 blank Paracetamol with aspirin
240411_Fizamol-11+1mgmLASS2_200mW_OD3_2s_36n_pos1_r3 fiz_ass1 blank Paracetamol with aspirin
240411_Fizamol-11+1mgmLASS2_200mW_OD3_2s_36n_pos2_r1 fiz_ass2 blank Paracetamol with aspirin
240411_Fizamol-11+1mgmLASS2_200mW_OD3_2s_36n_pos2_r2 fiz_ass2 blank Paracetamol with aspirin
240411_Fizamol-11+1mgmLASS2_200mW_OD3_2s_36n_pos2_r3 fiz_ass2 blank Paracetamol with aspirin
240411_Fizamol-11+1mgmLASS2_200mW_OD3_2s_36n_pos3_r1 fiz_ass3 blank Paracetamol with aspirin
240411_Fizamol-11+1mgmLASS2_200mW_OD3_2s_36n_pos3_r2 fiz_ass3 blank Paracetamol with aspirin
240411_Fizamol-11+1mgmLASS2_200mW_OD3_2s_36n_pos3_r3 fiz_ass3 blank Paracetamol with aspirin
240411_Fizamol-12gealtert_200mW_OD3_2s_36n_pos1_r1 fiz_b1 blank Paracetamol product
240411_Fizamol-12gealtert_200mW_OD3_2s_36n_pos1_r2 fiz_b1 blank Paracetamol product
240411_Fizamol-12gealtert_200mW_OD3_2s_36n_pos1_r3 fiz_b1 blank Paracetamol product
240411_Fizamol-12gealtert_200mW_OD3_2s_36n_pos2_r1 fiz_b2 blank Paracetamol product
240411_Fizamol-12gealtert_200mW_OD3_2s_36n_pos2_r2 fiz_b2 blank Paracetamol product
240411_Fizamol-12gealtert_200mW_OD3_2s_36n_pos2_r3 fiz_b2 blank Paracetamol product
240411_Fizamol-12gealtert_200mW_OD3_2s_36n_pos3_r1 fiz_b3 blank Paracetamol product
240411_Fizamol-12gealtert_200mW_OD3_2s_36n_pos3_r2 fiz_b3 blank Paracetamol product
240411_Fizamol-12gealtert_200mW_OD3_2s_36n_pos3_r3 fiz_b3 blank Paracetamol product
240411_Fizamol-11_200mW_OD3_2s_36n_pos1_r1 fiz_c1 blank Paracetamol product
240411_Fizamol-11_200mW_OD3_2s_36n_pos1_r2 fiz_c1 blank Paracetamol product
240411_Fizamol-11_200mW_OD3_2s_36n_pos1_r3 fiz_c1 blank Paracetamol product
240411_Fizamol-11_200mW_OD3_2s_36n_pos2_r1 fiz_c2 blank Paracetamol product
240411_Fizamol-11_200mW_OD3_2s_36n_pos2_r2 fiz_c2 blank Paracetamol product
240411_Fizamol-11_200mW_OD3_2s_36n_pos2_r3 fiz_c2 blank Paracetamol product
240411_Fizamol-11_200mW_OD3_2s_36n_pos3_r1 fiz_c3 blank Paracetamol product
240411_Fizamol-11_200mW_OD3_2s_36n_pos3_r2 fiz_c3 blank Paracetamol product
240411_Fizamol-11_200mW_OD3_2s_36n_pos3_r3 fiz_c3 blank Paracetamol product
240411_Fizamol-11+1mgmLcoffein_200mW_OD3_2s_36n_pos1_r1 fiz_caff1 blank Paracetamol with caffeine
240411_Fizamol-11+1mgmLcoffein_200mW_OD3_2s_36n_pos1_r2 fiz_caff1 blank Paracetamol with caffeine
240411_Fizamol-11+1mgmLcoffein_200mW_OD3_2s_36n_pos1_r3 fiz_caff1 blank Paracetamol with caffeine
240411_Fizamol-11+1mgmLcoffein_200mW_OD3_2s_36n_pos2_r1 fiz_caff2 blank Paracetamol with caffeine
240411_Fizamol-11+1mgmLcoffein_200mW_OD3_2s_36n_pos2_r2 fiz_caff2 blank Paracetamol with caffeine
240411_Fizamol-11+1mgmLcoffein_200mW_OD3_2s_36n_pos2_r3 fiz_caff2 blank Paracetamol with caffeine
240411_Fizamol-11+1mgmLcoffein_200mW_OD3_2s_36n_pos3_r1 fiz_caff3 blank Paracetamol with caffeine
240411_Fizamol-11+1mgmLcoffein_200mW_OD3_2s_36n_pos3_r2 fiz_caff3 blank Paracetamol with caffeine
240411_Fizamol-11+1mgmLcoffein_200mW_OD3_2s_36n_pos3_r3 fiz_caff3 blank Paracetamol with caffeine
240411_Fizamol-12_200mW_OD3_2s_36n_pos1_r1 fiz_d1 blank Paracetamol product
240411_Fizamol-12_200mW_OD3_2s_36n_pos1_r2 fiz_d1 blank Paracetamol product
240411_Fizamol-12_200mW_OD3_2s_36n_pos1_r3 fiz_d1 blank Paracetamol product
240411_Fizamol-12_200mW_OD3_2s_36n_pos2_r1 fiz_d2 blank Paracetamol product
240411_Fizamol-12_200mW_OD3_2s_36n_pos2_r2 fiz_d2 blank Paracetamol product
240411_Fizamol-12_200mW_OD3_2s_36n_pos2_r3 fiz_d2 blank Paracetamol product
240411_Fizamol-12_200mW_OD3_2s_36n_pos3_r1 fiz_d3 blank Paracetamol product
240411_Fizamol-12_200mW_OD3_2s_36n_pos3_r2 fiz_d3 blank Paracetamol product
240411_Fizamol-12_200mW_OD3_2s_36n_pos3_r3 fiz_d3 blank Paracetamol product
240412_Fizamol12-1_200mW_OD3_2s_36n_pos1_r1 fiz_e01 blank_e Paracetamol product
240412_Fizamol12-1_200mW_OD3_2s_36n_pos1_r2 fiz_e01 blank_e Paracetamol product
240412_Fizamol12-1_200mW_OD3_2s_36n_pos1_r3 fiz_e01 blank_e Paracetamol product
240412_Fizamol12-1_200mW_OD3_2s_36n_pos2_r1 fiz_e02 blank_e Paracetamol product
240412_Fizamol12-1_200mW_OD3_2s_36n_pos2_r2 fiz_e02 blank_e Paracetamol product
240412_Fizamol12-1_200mW_OD3_2s_36n_pos2_r3 fiz_e02 blank_e Paracetamol product
240412_Fizamol12-1_200mW_OD3_2s_36n_pos3_r1 fiz_e03 blank_e Paracetamol product
240412_Fizamol12-1_200mW_OD3_2s_36n_pos3_r2 fiz_e03 blank_e Paracetamol product
240412_Fizamol12-1_200mW_OD3_2s_36n_pos3_r3 fiz_e03 blank_e Paracetamol product
240412_Fizamol12-2_200mW_OD3_2s_36n_pos1_r1 fiz_e04 blank_e Paracetamol product
240412_Fizamol12-2_200mW_OD3_2s_36n_pos1_r2 fiz_e04 blank_e Paracetamol product
240412_Fizamol12-2_200mW_OD3_2s_36n_pos1_r3 fiz_e04 blank_e Paracetamol product
240412_Fizamol12-2_200mW_OD3_2s_36n_pos2_r1 fiz_e05 blank_e Paracetamol product
240412_Fizamol12-2_200mW_OD3_2s_36n_pos2_r2 fiz_e05 blank_e Paracetamol product
240412_Fizamol12-2_200mW_OD3_2s_36n_pos2_r3 fiz_e05 blank_e Paracetamol product
240412_Fizamol12-2_200mW_OD3_2s_36n_pos3_r1 fiz_e06 blank_e Paracetamol product
240412_Fizamol12-2_200mW_OD3_2s_36n_pos3_r2 fiz_e06 blank_e Paracetamol product
240412_Fizamol12-2_200mW_OD3_2s_36n_pos3_r3 fiz_e06 blank_e Paracetamol product
240412_Fizamol12-3_200mW_OD3_2s_36n_pos1_r1 fiz_e07 blank_e Paracetamol product
240412_Fizamol12-3_200mW_OD3_2s_36n_pos1_r2 fiz_e07 blank_e Paracetamol product
240412_Fizamol12-3_200mW_OD3_2s_36n_pos1_r3 fiz_e07 blank_e Paracetamol product
240412_Fizamol12-3_200mW_OD3_2s_36n_pos2_r1 fiz_e08 blank_e Paracetamol product
240412_Fizamol12-3_200mW_OD3_2s_36n_pos2_r2 fiz_e08 blank_e Paracetamol product
240412_Fizamol12-3_200mW_OD3_2s_36n_pos2_r3 fiz_e08 blank_e Paracetamol product
240412_Fizamol12-3_200mW_OD3_2s_36n_pos3_r1 fiz_e09 blank_e Paracetamol product
240412_Fizamol12-3_200mW_OD3_2s_36n_pos3_r2 fiz_e09 blank_e Paracetamol product
240412_Fizamol12-3_200mW_OD3_2s_36n_pos3_r3 fiz_e09 blank_e Paracetamol product
240412_Fizamol12-4_200mW_OD3_2s_36n_pos1_r1 fiz_e10 blank_e Paracetamol product
240412_Fizamol12-4_200mW_OD3_2s_36n_pos1_r2 fiz_e10 blank_e Paracetamol product
240412_Fizamol12-4_200mW_OD3_2s_36n_pos1_r3 fiz_e10 blank_e Paracetamol product
240412_Fizamol12-4_200mW_OD3_2s_36n_pos2_r1 fiz_e11 blank_e Paracetamol product
240412_Fizamol12-4_200mW_OD3_2s_36n_pos2_r2 fiz_e11 blank_e Paracetamol product
240412_Fizamol12-4_200mW_OD3_2s_36n_pos2_r3 fiz_e11 blank_e Paracetamol product
240412_Fizamol12-4_200mW_OD3_2s_36n_pos3_r1 fiz_e12 blank_e Paracetamol product
240412_Fizamol12-4_200mW_OD3_2s_36n_pos3_r2 fiz_e12 blank_e Paracetamol product
240412_Fizamol12-4_200mW_OD3_2s_36n_pos3_r3 fiz_e12 blank_e Paracetamol product
240412_Paracetamol-10mgmL_200mW_OD3_2s_36n_pos1_r1 par_1 blank Paracetamol standard
240412_Paracetamol-10mgmL_200mW_OD3_2s_36n_pos1_r2 par_1 blank Paracetamol standard
240412_Paracetamol-10mgmL_200mW_OD3_2s_36n_pos1_r3 par_1 blank Paracetamol standard
240412_Paracetamol-10mgmL_200mW_OD3_2s_36n_pos4_r1 par_2 blank Paracetamol standard
240412_Paracetamol-10mgmL_200mW_OD3_2s_36n_pos4_r2 par_2 blank Paracetamol standard
240412_Paracetamol-10mgmL_200mW_OD3_2s_36n_pos4_r3 par_2 blank Paracetamol standard
240412_Paracetamol-10mgmL_200mW_OD3_2s_36n_pos3_r1 par_3 blank Paracetamol standard
240412_Paracetamol-10mgmL_200mW_OD3_2s_36n_pos3_r2 par_3 blank Paracetamol standard
240412_Paracetamol-10mgmL_200mW_OD3_2s_36n_pos3_r3 par_3 blank Paracetamol standard 
raman_workflow_settings <- list(
  RamanSettings_AverageSpectra_StreamFind(),
  RamanSettings_SubtractBlankSpectra_StreamFind(),
  RamanSettings_SmoothSpectra_savgol(fl = 21, forder = 4, dorder = 0),
  RamanSettings_DeleteSpectraSection_StreamFind(list("shift" = c(-100, 350))),
  RamanSettings_DeleteSpectraSection_StreamFind(list("shift" = c(1800, 2500))),
  RamanSettings_CorrectSpectraBaseline_airpls(lambda = 45, differences = 1, itermax = 30),
  RamanSettings_NormalizeSpectra_minmax(),
  RamanSettings_NormalizeSpectra_blockweight()
)

raman$add_settings(raman_workflow_settings)

raman$print_workflow()

Workflow
 1: AverageSpectra (StreamFind)
 2: SubtractBlankSpectra (StreamFind)
 3: SmoothSpectra (savgol)
 4: DeleteSpectraSection (StreamFind)
 5: DeleteSpectraSection (StreamFind)
 6: CorrectSpectraBaseline (airpls)
 7: NormalizeSpectra (minmax)
 8: NormalizeSpectra (blockweight)
raman$run_workflow()
raman$plot_spectra()

Pre-processed Raman spectra for analysis replicate. 

raman$get_spectra()[1:10, ]
    analysis replicate    shift   intensity    blank baseline      raw
      <char>    <char>    <num>       <num>    <num>    <num>    <num>
 1:    ass_1     ass_1 350.3578 0.000000000 47160.00 9148.558 8954.093
 2:    ass_1     ass_1 353.3808 0.000000000 47245.78 9152.879 9038.648
 3:    ass_1     ass_1 356.4008 0.000000000 47054.00 9159.943 9080.207
 4:    ass_1     ass_1 359.4177 0.000000000 46981.00 9168.890 9106.521
 5:    ass_1     ass_1 362.4336 0.000000000 47145.78 9179.299 9176.353
 6:    ass_1     ass_1 365.4485 0.002669691 46989.00 9189.776 9229.674
 7:    ass_1     ass_1 368.4604 0.004423876 46941.89 9199.360 9265.474
 8:    ass_1     ass_1 371.4691 0.005247175 46765.00 9208.944 9287.362
 9:    ass_1     ass_1 374.4769 0.006030455 47019.67 9218.528 9308.653
10:    ass_1     ass_1 377.4838 0.007325727 46920.44 9228.112 9337.595

Fusion 

ms_spec_mat <- ms$get_spectra_matrix()
raman_spec_mat <- raman$get_spectra_matrix()
fused_mat <- cbind(ms_spec_mat, raman_spec_mat)
# The matrix is mean centered using the mdatools R package
fused_mat <- mdatools::prep.autoscale(fused_mat, center = TRUE, scale = FALSE)

Statistic analysis

Unsupervised

Principle Components Analysis (PCA) can be used for unsupervised evaluation, meaning that we assume that the main (or train) set of analyses are of good quality and we test new analyses to evaluate the proximity to the main set. One could say that it is a supervised approach but in the sense that we assume the quality of the main set. Yet, we are not classifying the possible deviation of the new analyses which would be a clear supervised approach, as we show in the next sub chapter.

main_set <- fused_mat[c(7:9, 16:21, 25:33), ]
rownames(main_set)
 [1] "fiz_a1"  "fiz_a2"  "fiz_a3"  "fiz_b1"  "fiz_b2"  "fiz_b3"  "fiz_c1" 
 [8] "fiz_c2"  "fiz_c3"  "fiz_d1"  "fiz_d2"  "fiz_d3"  "fiz_e01" "fiz_e02"
[15] "fiz_e03" "fiz_e04" "fiz_e05" "fiz_e06"
test_set <- fused_mat[c(1:6, 10:15, 22:24, 34:42), ]
rownames(test_set)
 [1] "ass_1"     "ass_2"     "ass_3"     "caff_1"    "caff_2"    "caff_3"   
 [7] "fiz_acid1" "fiz_acid2" "fiz_acid3" "fiz_ass1"  "fiz_ass2"  "fiz_ass3" 
[13] "fiz_caff1" "fiz_caff2" "fiz_caff3" "fiz_e07"   "fiz_e08"   "fiz_e09"  
[19] "fiz_e10"   "fiz_e11"   "fiz_e12"   "par_1"     "par_2"     "par_3"    
stat <- StatisticEngine$new(data = main_set)
# The alpha and gamma parameters are used to evaluate the model limits
stat$process(StatisticSettings_MakeModel_pca_mdatools(ncomp = 3, alpha = 1E-4, gamma = 1E-5))
# Original plot from mdatools R package
plot(stat$model)
PCA model (native plot from mdatools R package).

PCA model (native plot from mdatools R package). 

stat$predict(test_set)
stat$plot_predicted_distances()

PCA model prediction distances. For more information about the distances plese consult the mdatools guide in https://mdatools.com/docs/pca--distances-and-limits.html.

Supervised (classification)

The k-nearest neighbors (KNN) can be used for classification of analyses based on pre-classified training analyses.

train_set <- fused_mat[unique(c(grep("1", rownames(fused_mat)), grep("2", rownames(fused_mat)))), ]
train_set <- train_set[order(rownames(train_set)), ]
rownames(train_set)
 [1] "ass_1"     "ass_2"     "caff_1"    "caff_2"    "fiz_a1"    "fiz_a2"   
 [7] "fiz_acid1" "fiz_acid2" "fiz_ass1"  "fiz_ass2"  "fiz_b1"    "fiz_b2"   
[13] "fiz_c1"    "fiz_c2"    "fiz_caff1" "fiz_caff2" "fiz_d1"    "fiz_d2"   
[19] "fiz_e01"   "fiz_e02"   "fiz_e10"   "fiz_e11"   "fiz_e12"   "par_1"    
[25] "par_2"    
test_set <- fused_mat[unique(grep("3|4|5|6|7|8|9", rownames(fused_mat))), ]
rownames(test_set)
 [1] "ass_3"     "caff_3"    "fiz_a3"    "fiz_acid3" "fiz_ass3"  "fiz_b3"   
 [7] "fiz_c3"    "fiz_caff3" "fiz_d3"    "fiz_e03"   "fiz_e04"   "fiz_e05"  
[13] "fiz_e06"   "fiz_e07"   "fiz_e08"   "fiz_e09"   "par_3"    
labels <- c(rep("ass", 2), rep("caff", 2), rep("fiz", 2), rep("fiz_acid", 2), rep("fiz_ass", 2),
  rep("fiz", 2), rep("fiz", 2), rep("fiz_caff", 2), rep("fiz", 7), rep("par", 2))
stat2 <- StatisticEngine$new(data = train_set)
stat2$add_classes(labels)
stat2$process(StatisticSettings_PrepareClassification_knn(k = 3))
stat2$classify(test_set)
stat2$classification_results
     analysis    class probability
       <char>   <fctr>       <num>
 1:     ass_3      ass         0.7
 2:    caff_3     caff         0.7
 3:    fiz_a3      fiz         1.0
 4: fiz_acid3 fiz_acid         0.7
 5:  fiz_ass3  fiz_ass         0.7
 6:    fiz_b3      fiz         0.7
 7:    fiz_c3      fiz         1.0
 8: fiz_caff3 fiz_caff         0.7
 9:    fiz_d3      fiz         1.0
10:   fiz_e03      fiz         1.0
11:   fiz_e04      fiz         1.0
12:   fiz_e05      fiz         1.0
13:   fiz_e06      fiz         1.0
14:   fiz_e07      fiz         1.0
15:   fiz_e08      fiz         1.0
16:   fiz_e09      fiz         1.0
17:     par_3      par         0.7

Only MS 

ms_spec_mat <- mdatools::prep.autoscale(ms_spec_mat, center = TRUE, scale = FALSE)
main_set_ms <- ms_spec_mat[c(7:9, 16:21, 25:33), ]
test_set_ms <- ms_spec_mat[c(1:6, 10:15, 22:24, 34:42), ]
stat_ms <- StatisticEngine$new(data = main_set_ms)
stat_ms$process(StatisticSettings_MakeModel_pca_mdatools(ncomp = 3, alpha = 1E-4, gamma = 1E-5))
plot(stat_ms$model)
PCA model for MS data only (native plot from mdatools R package).

PCA model for MS data only (native plot from mdatools R package). 

stat_ms$predict(test_set_ms)
stat_ms$plot_predicted_distances()

PCA model prediction distances for only MS data.

Using MS data only for evaluation of quality deviations would not separate completely the analyses when compared to fused MS and Raman data. Thus, the contribution of Raman spectroscopy to explain structural deviations brings an advantage for routine quality evaluation of paracetamol and other pharmaceuticals.

Only Raman 

raman_spec_mat <- mdatools::prep.autoscale(raman_spec_mat, center = TRUE, scale = FALSE)
main_set_raman <- raman_spec_mat[c(7:9, 16:21, 25:33), ]
test_set_raman <- raman_spec_mat[c(1:6, 10:15, 22:24, 34:42), ]
stat_raman <- StatisticEngine$new(data = main_set_raman)
stat_raman$process(StatisticSettings_MakeModel_pca_mdatools(ncomp = 3, alpha = 1E-4, gamma = 1E-5))
plot(stat_raman$model)
PCA model for Raman data only (native plot from mdatools R package).

PCA model for Raman data only (native plot from mdatools R package). 

stat_raman$predict(test_set_raman)
stat_raman$plot_predicted_distances()

PCA model prediction distances for only Raman data.

In the case of only using Raman data for evaluation of quality deviations, the separation of the analyses is clearer than when using fused MS and Raman data. This is due to the fact that the Raman data is more sensitive to structural deviations in the analyses. The lack of aspirin and acetic acid signals in the MS data probably contributed to the less clear separation of the analyses when using only MS data. On the contrary, because the signal of caffeine (m/z 194 Da) was visible in the MS data, a separation of the caffeine contaminated analyses was obtained also for MS only data. MS data is more precise when the goal is identification of the active product ingredient (i.e, paracetamol) therefore, the fusion of MS and Raman data is recommended for quality evaluation of pharmaceuticals as both techniques are complementary.

Quantification with Raman 

raman_quant$plot_spectra(colorBy = "replicates")

Raw averaged Raman spectra for each analysis replicate. 

raman_workflow_settings <- list(
  RamanSettings_AverageSpectra_StreamFind(),
  RamanSettings_SubtractBlankSpectra_StreamFind(),
  RamanSettings_SmoothSpectra_savgol(fl = 21, forder = 4, dorder = 0),
  RamanSettings_DeleteSpectraSection_StreamFind(list("shift" = c(-100, 350))),
  RamanSettings_DeleteSpectraSection_StreamFind(list("shift" = c(1800, 2500))),
  RamanSettings_CorrectSpectraBaseline_airpls(lambda = 45, differences = 1, itermax = 30)
)

raman_quant$add_settings(raman_workflow_settings)

raman_quant$print_workflow()

Workflow
 1: AverageSpectra (StreamFind)
 2: SubtractBlankSpectra (StreamFind)
 3: SmoothSpectra (savgol)
 4: DeleteSpectraSection (StreamFind)
 5: DeleteSpectraSection (StreamFind)
 6: CorrectSpectraBaseline (airpls)
raman_quant$run_workflow()
raman_quant$plot_spectra()

Pre-processed Raman spectra for analysis replicate.

Applying MCR-ALS

The quantification of paracetamol from the Raman spectra is performed using the Multivariate Curve Resolution (MCR) with Alternating Least Squares (ALS) method via integration of the mdatools R package.

stat3 <- StatisticEngine$new(data = raman_quant$get_spectra_matrix())
stat3$add_concentrations(c(1, 2.5, 5.0, 7.5, 15.0, NA_real_)) # add concentrations, with NA for unknown
stat3$process(StatisticSettings_MakeModel_mcrals_mdatools(ncomp = 3))
summary(stat3$model)

Summary for MCR ALS case (class mcrals)

Constraints for spectra:
 - none


Constraints for contributions:
 - none

       Expvar Cumexpvar
Comp 1  21.44     21.44
Comp 2  60.73     82.17
Comp 3  17.80     99.97
stat3$plot_model_resolved_spectra()

Resolved spectra for each component and the spectra for each analysis replicate (i.e., each concentration). 

stat3$plot_model_contributions()

Contributions for each analysis replicate.

The quantify method can be used to estimate the concentration of the paracetamol analyses with unknown concentration. The quantification is applied to each component, returning a list with the r square of the linear model and the estimated concentration as data.table. Note that the explained variance for each component is important to evaluate the calculated concentration. The best estimation is from the component with the combined explained variance and r square closer to 100 and 1, respectively.

stat3$quantify()
$`Comp 1`
$`Comp 1`$r_squared
[1] 0.989119

$`Comp 1`$quantification
        analysis  mcr_value concentration
          <char>      <num>         <num>
1: cali_010_mgml   2.833177       1.00000
2: cali_025_mgml   0.000000       2.50000
3: cali_050_mgml 196.055198       5.00000
4: cali_075_mgml 310.359083       7.50000
5: cali_150_mgml 711.390475      15.00000
6:         par_3 888.288779      18.25022


$`Comp 2`
$`Comp 2`$r_squared
[1] 0.9735507

$`Comp 2`$quantification
        analysis  mcr_value concentration
          <char>      <num>         <num>
1: cali_010_mgml    0.00000      1.000000
2: cali_025_mgml   16.13659      2.500000
3: cali_050_mgml  380.34701      5.000000
4: cali_075_mgml  566.07595      7.500000
5: cali_150_mgml 1846.37336     15.000000
6:         par_3  815.00755      8.015858


$`Comp 3`
$`Comp 3`$r_squared
[1] 0.9632655

$`Comp 3`$quantification
        analysis mcr_value concentration
          <char>     <num>         <num>
1: cali_010_mgml  145.2248      1.000000
2: cali_025_mgml  340.0791      2.500000
3: cali_050_mgml  410.6169      5.000000
4: cali_075_mgml  642.4244      7.500000
5: cali_150_mgml  942.9335     15.000000
6:         par_3  684.2477      9.514703