Supporting Information

Rapid Discrimination of Malaria and Dengue Infected Patient Sera using Raman Spectroscopy

Sandip K. Patel1, Nishant Rajora1, Saurabh Kumar1, Aditi Sahu2, Sanjay K. Kochar3, C. Murali Krishna2* and Sanjeeva Srivastava1*

1 Department of Biosciences and Bioengineering, Indian Institute of Technology Bombay, Powai, Mumbai 400076, India

2 Chilakapati lab, ACTREC, Tata Memorial Center, Kharghar, Navi Mumbai-410210, India

3 Department of Medicine, Malaria Research Center, S.P. Medical College, Bikaner 334003, India

*Correspondence: 1. Professor Sanjeeva Srivastava, Department of Biosciences and Bioengineering, Indian Institute of Technology Bombay, Powai, Mumbai 400076, India E-mail: [email protected]; Phone: +91-22-2576-7779, Fax: +91-22-2572-3480

2. Professor Chilakapati Murali Krishna, Chilakapati lab, ACTREC, Tata Memorial Center, Kharghar, Navi Mumbai-410210, India E-mail: [email protected], [email protected]

1. SI Materials and Methods (pn:2)

2. TableS1: Investigation of hematological and biochemical parameters of the dengue and malaria patient sera and healthy subjected included in the study (pn:4)

3. Table S2: Complete details of all statistically significant (p < 0.05 and fold change <1.5) altered metabolites in malaria and dengue obtained from mass spectrometry (Q-TOF) analysis. (pn:5)

SI Materials and Methods Subject Recruitment and Sample Collection. Blood samples were collected from 37 malaria (27 for model generation, 12 for validation; 2 samples were overlapping) and 39 dengue (29 for model generation and 12 for validation; 2 samples were overlapping) patients and 54 HC patients. Malaria cases were confirmed by the thick blood smear microscopy method and RDT, while dengue infections were diagnosed by an IgM antibody capture enzyme-linked immunosorbent assay. Raman spectroscopy Spectra acquisition: After passive thawing, samples were subjected to Raman spectroscopy by placing 30 μl volume on calcium fluoride (CaF2) window and spectra were recorded using fiber optic Raman microprobe (Horiba-Jobin-Yvon, France). This system consists of laser (785 nm, Process Instruments) as an excitation source and a HE 785 spectrograph (Horiba-Jobin-Yvon, France) coupled with CCD (Synapse, Horiba-Jobin-Yvon) as dispersion and detection elements, respectively. Optical filtering of unwanted noise, including Rayleigh signals, is accomplished through ‘Superhead’, the other component of the system. Optical fibers were employed to carry the incident light from the excitation source to the sample and to collect the Raman scattered light from the sample to the detection system. The Raman microprobe was assembled by coupling a 40× microscope objective (Nikon, Japan) to the superhead. Spectra were acquired in the range of 500−3500 cm−1 for 20 s and averaged over three accumulations, acquisition details, laser power = 30 mW, and excitation wavelength (λex) = 785 nm. Eight spectra were recorded from each sample 1. Data analysis: Raman data analysis was performed following previously described protocol 2. Briefly, Raman spectra were corrected for CCD-response and background spectral contaminations from substrate and fiber signals. For multivariate data analysis, first derivative of the spectra was computed using the Savitzky-Golay method (window size 3). Derivatized spectra were interpolated in the region of 800-1800 cm-1 and subjected to supervised principal components linear discriminant (PC-LDA) analysis. For supervised PC-LDA approach, standard models of pathologically certified groups: malaria, dengue, and HC were developed, and analysis was carried out in 2- and 3-model systems. PC- LDA was followed by leave-one-out cross validation (LOOCV). Test predictions were carried out on the 3-model system. PC-LDA, LOOCV, and test prediction analyses were performed using a MATLAB (Mathworks Inc.) based in-house software 3. The resulting PC-LDA analysis was presented as scatter plots and confusion matrix, where the diagonal elements represent the true positive predictions while non-diagonal elements represent misclassifications across groups. The efficiency of the RS model for discriminating malaria and dengue with HC was analysed using ROC [plot of true positives (sensitivity) vs. false positives (1- speciﬁcity)] plotted using GraphPad Prism software package (version 6.02). For spectral comparisons, the background-subtracted spectra were baseline-corrected by fitting a fifth order polynomial function, smoothed (Savitzky–Golay, 3) and vector-normalized to compute the average representative spectra of each pathological group.

Mass spectrometry Metabolite extraction: Serum samples were extracted in methanol in a ratio of 1: 4 (v/v) following previously described protocol 4. Mass spectrometry runs parameters and data acquisitions: Metabolites were analyzed using an Agilent 1260 Infinity HPLC system coupled to an Agilent 6550 HRLC system. Metabolite (1µl) was separated at a gradient of 5% mobile phase B increasing linearly to 100% B in 50 min and was held at until 60 min, mobile phase A: 0.1 % formic acid in water, mobile phase B: 0.1 % formic acid in 90% acetonitrile, flow-rate 0.3 ml/min, temperature 40°C. Agilent MassHunterTM software was used for untargeted data acquisition in centroid mode over the mass range m/z 50–1000 with a scan rate of 1.5 spectra/sec. Data processing and analysis: Data was deconvoluted into individual chemical peaks in Agilent MassHunter™ Qualitative Analysis B.05.01 using molecular feature extractor (MFE) with an absolute height filter set to 5,000 counts. A separate, complementary “targeted” data mining approach was used that was based on a list of annotated compounds with empirical formulas. An algorithm, “Find by Mass” was used to find compounds in LC/MS data files. The list of compounds and their associated formulas was derived from METLIN. Results of the analyses was a series of extracted ion chromatograms (EICs) that were saved as CEF files and were used for subsequent statistical analysis and data visualization in mass profiler professional (MPP) version 12.6 software (Agilent Technologies, Santa Clara, CA). A complete list of metabolites expressed differentially (fold change > 2; p < 0.05) in malaria and dengue as compared to HC is tabulated in Table S2.

TableS1: Investigation of hematological and biochemical parameters of the dengue and malaria patient sera and healthy subjected included in the study

Healthy (n=54) Malaria (n=37) p-value Dengue (n=39) p-value Mean ± SD (Max - Min) Mean ± SD (Max - Min) Mean ± SD (Max - Min)

Sex F=12; M=42 F=6; M=31 F=7; M=32

Age 21.5±4.6(35-18) 29.1±10.8(56-15) 28.7±9.7(55-16)

Haematological parameters Hemoglobin (g/dl) 12.3±1.6(14.3-8.1) 9.4±3.0(14.2-3.2) 1.00E-05 12.8±2.4(18.8-5.0) 0.242 56191.9±29025.1(122000- Platelets/μl 68805.6±40651.7(200000-39300) 0.1052 30843.6±28085.3(104000-2700) 1.00E-05 2600) Biochemical parameters Creatinine (mg/dl) 0.8 0.1(1.07-0.51) 2.0±1.4(4.6-0.0) 1.00E-05 5.5±15.4(85. -0.7) 1.00E-04

Total bilirubin (mg%) 1.5±2.4(9.0-0.25) 1.5±1.0(4.6-0.6) 1.00E-05 1.3±1.1(6.6-0.6) 6.94E-4

Urea (mg/dl) 33.6±9.0(55.4-21.2) 70.6±46.1(156.38-21.0) 4.2E-04 47.6±25.4(126.0-22.0) 0.141

AST (1U/l) 25.6±7.5(40.0-12.38) 32.9±7.7(51.0-17.6) 6.00E-05 39.5±21.6(89.0-13.0) 4.00E-04

ALT (1U/l) 28.8±10.3(50-12.38) 49.3±47.0(201-12.4) 3.6E-05 46.5±31.5(194.2-20.0) 1.00E-05

ALP (µkat/l) 67.5±28.6(110.0-17.21) 168.8±137.8(501-12.0) 1.00E-05 121.4±69.9(400.0-59.0) 1.00E-05

Table S2: Complete details of all statistically significant (p < 0.05 and fold change > 2) altered metabolites in malaria and dengue obtained from mass spectrometry (Q-TOF) analysis.

Regulation Regulation Compound FC (D vs H) FC (M vs H) Mass CAS Number KEGG ID (D vs H) (M vs H) (+/-)14,15-EpETrE 7.22706 up 1.09E+07 up 383.0678 72509-76-3 C06995 Phosphoric acid -1 down 962662.7 up 176.0437 923-37-5 D-Glucose 15.772747 up 860830.8 up 200.0315 57728-59-3 Leucine -1 down 817288.44 up 614.1229 153-18-4 C05625 D-Galactose 30.251202 up 770244.25 up 449.3047 126-27-2 C12552 Histidine 139.3417 up 746023.5 up 244.0571 54955-36-1 myo-Inositol -1 down 695352.44 up 310.15 60-99-1 C07192 Asparagine 24.431307 up 694322.7 up 365.0577 103237-52-1 Acetoacetic acid 158917.64 up 641903.1 up 208.0848 487-90-1 C00931 Benzoic acid -1 down 641887 up 776.5494 473-32-5 Dihydroxyacetone (glycerone) 98.77884 up 431303.44 up 445.0632 19046-78-7 C03794 Ethanolamine -1 down 404604.28 up 384.2424 116285-37-1 Ceramide (d18:1/12:0) -1 down 377302.47 up 262.0682 2627-69-2 Maltose 16.973713 up 366541.22 up 190.0025 34875-87-1 Glyceric acid 91836.63 up 360219.6 up 258.0363 54955-32-7 Hypoxanthine -1 down 337194.22 up 187.0237 6061-96-7 Glycolaldehyde 1069.2494 up 313634.8 up 427.0613 80210-62-4 C08114 Inosine -1 down 292967.16 up 356.1999 83-43-2 C07197 Creatine 1195.8191 up 272420.75 up 199.0262 4432-31-9 Canavanine -1 down 271589.72 up 477.2118 C11131 Pyridoxine (Vitamin B6) -1 down 260782.05 up 908.6259 31867-59-1 C03543 Kynurenine -1 down 230422.62 up 292.1772 51781-06-7 C06874 Glucosamine 3.7021706 up 225207.48 up 462.2861 483-18-1 C09421

L-DOPA 4.486463 up 203769.89 up 506.3114 C11999 QH2 -1 down 193540.36 up 135.0542 21768-45-6 C06056 Dipalmitoylphosphatidic acid 61.05689 up 193439.83 up 775.5522 98677-33-9 Ethanol 3.7754045 up 189612.4 up 487.3262 C03640 Bilirubin 61.97075 up 184579.55 up 299.1878 549-91-7 C11816 Biliverdin IX -1 down 184297.17 up 298.1259 159126-30-4 Homogentisic acid -1 down 177600.52 up 327.2341 C11898 Trimethylamine -1 down 163461.58 up 375.3042 29560-24-5 C05440 N-Acetyl-L-glutamic acid -1 down 160658.12 up 762.4624 110671-78-8 Indoleacetaldehyde -1 down 152178.64 up 228.0737 04-05-5627 p-Hydroxyphenylacetic acid -1 down 150685.14 up 374.1189 9005-82-7 C00718 5-Formiminotetrahydrofolic acid -1 down 149412.17 up 701.1946 92137-84-3 gamma-L-Glutamyl-L-cysteine -1 down 143023.11 up 374.2358 357-56-2 Amylose -1 down 142041.17 up 360.2204 309-29-5 Acetoin -1 down 139204.97 up 465.3025 1256-86-6 Dihydrosphingosine -1 down 134185.98 up 301.2186 301-02-0 Deoxycytidine -1 down 128443.78 up 607.2541 30783-27-8 tartaric acid -1 down 125408.82 up 322.1497 1240-15-9 Porphobilinogen 3.5441656 up 117297.08 up 545.2386 67368-29-0 3-Dehydroquinic acid -1 down 116367.84 up 591.2348 139481-59-7 Indole-3-ethanol 13.332219 up 115564.016 up 764.511 2394-68-5 L-Fucose 5.492009 up 106403.94 up 297.0827 68498-25-9 Dimethylglycine -1 down 103165.57 up 245.0554 35607-35-3 2-Methylbutyryl CoA 9.407067 up 101408.42 up 485.1694 22135-79-1 L-3,5-Diiodotyrosine -1 down 99026.016 up 423.2664 116666-60-5 Protoporphyrinogen IX -1 down 97958.8 up 668.3989 C01946 N(pai)-Methyl-L-histidine -1 down 97010.62 up 182.0876 70052-12-9 C07997 Dihydrostreptomycin 6-phosphate 533.8753 up 96749.97 up 356.2284 24353-18-2 Neamine (Neomycin A) -1 down 95421.61 up 581.1878 C11663

Ouabain 3.5833495 up 89564.28 up 462.3272 C01943 Octanal -1 down 88078.38 up 224.9871 66266-75-9 Allantoin -1 down 76969.87 up 470.8226 300-39-0 C01060 5alpha-androstane 17.322834 up 74055.984 up 308.2126 70805-84-4 Piroxicam -1 down 72275.266 up 285.1295 613-11-6 C05721 Cilastatin -1 down 72072.12 up 479.1408 136665-44-6 Ribonic acid -1 down 70599.5 up 370.0869 126702-18-9 Aldosterone -1 down 70284.164 up 426.2292 116285-36-0 Deoxyribose -1 down 70039.836 up 628.2316 478-61-5 pentanamide -1 down 69290.77 up 606.2461 635-65-4 C00486 4,4-Dimethyl-14a-hydroxymethyl-5a-cholesta-8,24- dien-3b-ol -1 down 67143.836 up 543.1 107187-86-0 Oleandomycin -1 down 66254.984 up 583.2283 67030-59-5 Pyrazinamide -1 down 65082.008 up 571.4176 1065-31-2 Trimethoprim -1 down 63527.824 up 494.1338 522-53-2 Staurosporine -1 down 63297.945 up 280.0857 104328-21-4 Mefenamic acid -1 down 62767.406 up 517.1966 76630-71-2 protoporphyrin IX -1 down 62695.25 up 218.0927 64111-04-2 Thromboxane -1 down 61362.973 up 314.1632 105115-77-3 3-Aminopropanal -1 down 61022.46 up 132.0538 70-47-3 C00152 2-Hydroxyadipic acid -1 down 61001.125 up 392.2086 42595-88-0 4-Methylpentanal -1 down 60799.84 up 348.1959 562-26-5 6-Mercaptopurine -1 down 60759.78 up 223.0789 80983-35-3 Phenylethylamine -1 down 60602.14 up 471.3136 50679-08-8 C07463 1-Methyladenosine -1 down 59819.336 up 275.1282 101948-35-0 N-Acetylarylamine 226.7527 up 56755.7 up 357.198 20594-83-6 C07251 N1-Acetylspermine 10.344573 up 55526.324 up 436.1176 54143-55-4 C07001 Lithocholic acid taurine conjugate -1 down 54987.375 up 652.2493 86154-18-9 Pimelic acid 1549.0315 up 54837.53 up 175.0624 42013-20-7

Lauric acid -1 down 54813.688 up 335.1765 118-42-3 C07043 Ne-Methyl-L-lysine 48.77337 up 54651.453 up 415.2687 89365-50-4 C07241 Anhydrotetracycline -1 down 53943.09 up 329.1759 32501-12-5 Cytarabine 3.0757234 up 52705.473 up 78.0111 62-74-8 Cholic acid glucuronide -1 down 52379.3 up 444.1956 66164-07-6 4-Guanidinobutanamide 3.585405 up 52234.25 up 327.2186 53016-31-2 Glucosylsphingosine -1 down 51171.3 up 652.4448 71065-87-7 C00416 Guanidinosuccinic Acid 16.01151 up 50947.863 up 252.1512 37242-41-4 D-Leucic acid 1393.9375 up 50827.066 up 310.1918 3591-17-1 N-Glycolylneuraminic acid 73634.03 up 49321.746 up 137.0444 100937-53-9 Adenosine tetraphosphate -1 down 47701.504 up 610.3379 162518-57-2 Undecaprenyl diphosphate -1 down 47058.42 up 340.1804 81276-03-1 C14771 20-hydroxy-LTE4 -1 down 46962.645 up 220.1573 721-50-6 C07531 SM(d18:1/0:0) 11.055705 up 46618.58 up 409.3312 1973-61-1 Taurolithocholic acid 3-sulfate 13.190237 up 44665.66 up 303.0477 43210-67-9 Glucosaminic acid -1 down 43252.89 up 116.0468 533-67-5 C01801 Deoxystreptomycin 3.4970624 up 42008.832 up 569.2382 34097-34-2 C03755 N6-(1,2-dicarboxyethyl)-AMP -1 down 41071.54 up 351.0416 26049-94-5 Octopine 16.685959 up 40842.496 up 511.2489 118448-54-7 Tetrahydropteroyltri-L-glutamate -1 down 40602.082 up 313.218 1164-98-3 C05485 3-Carboxy-4-methyl-2-oxopentanoate -1 down 40496.125 up 580.3878 66551-60-8 C05313 6,7-Dimethyl-8-(1-D-ribityl) lumazine -1 down 40274.867 up 340.1006 84692-89-7 5-Methyltetrahydropteroyltri-L-glutamate 3.7074554 up 40251.203 up 340.1657 53-03-2 C07370 a-N-Acetylneuraminyl-2,6-b-D-galactosyl-1,4-N- acetyl-b-D-glucosamine -1 down 39417.695 up 459.2521 199875-69-9 Norethindrone -1 down 35241.348 up 293.2141 514-65-8 C07941 3-Hexaprenyl-4,5-Dihydroxybenzoic acid -1 down 34533.69 up 236.0989 337-47-3 19-Oxotestosterone -1 down 34417.215 up 199.0622 484-29-7 C10660 3-Hexaprenyl-4-hydroxy-5-methoxybenzoic acid 3.6370614 up 33926.08 up 296.1772 4245-41-4

Galactosylglycerol -4.8210998 down 33732.152 up 129.054 585-23-9 Ergosta-5,7,22,24(28)-tetraene-3beta-ol -1 down 33628.246 up 527.178 76155-56-1 5beta-Cyprinolsulfate -1 down 33118.207 up 322.1456 99473-17-3 21-Hydroxypregnenolone -1 down 33036.215 up 255.1618 42576-09-0 Aerobactin 515.668 up 32784.77 up 357.2295 5633-20-5 C07360 Vanillylmandelic acid -1 down 31890.777 up 306.1735 130-95-0 C06526 3-Methoxy-4-hydroxyphenylethylene glycol -1 down 31041.984 up 330.1505 2064-15-5 Rutin -1 down 30880.545 up 382.1521 19216-56-9 C07368 4-Hydroxystyrene -1 down 30626.695 up 328.1288 84166-50-7 Tetrahydropteridine -1 down 30017.479 up 182.0688 710-77-0 Leucomethylene blue (Reduced Methylene Blue) 14.396367 up 29902.748 up 252.1147 51481-61-9 D00295 Vitamin K1 2,3-epoxide -1 down 29593.076 up 211.0408 13255-50-0 4-Hydroxy-L-threonine -1 down 29400.607 up 350.1993 42971-09-5 D01371 3-O-Sulfogalactosylceramide -1 down 28670.352 up 299.1851 24379-94-0 Galabiosylceramide (d18:1/20:0) -1 down 28540.803 up 294.1385 434-22-0 C07254 Galabiosylceramide (d18:1/25:0) -1 down 27495.596 up 315.2335 6724-53-4 Terephthalic acid -3.526455 down 27171.973 up 490.2205 129518-39-4 Cuscohygrine -4.716697 down 27090.854 up 873.1572 03-02-6712 C01033 Quinine 18.67019 up 26895.912 up 281.1064 66357-25-3 Cinchonine 3.8019311 up 26846.586 up 338.2234 69557-95-5 C12859 alpha-Erythroidine -1 down 26492.957 up 472.2492 68780-73-4 Ajmaline -1 down 26413.865 up 448.1166 73322-71-1 C11315 Tetracycline -1 down 25767.586 up 426.1427 C02811 Erythromycin B -1 down 25285.594 up 410.1745 93957-54-1 C07014 Ceftriaxone -1 down 24944.941 up 520.3165 03-06-6990 C06694 Fusidic acid -1 down 24856.5 up 354.1338 6620-60-6 D01818 Diethanolamine -1 down 24710.822 up 528.8673 534-51-0 Acebutolol 3.841703 up 24631.418 up 391.212 66575-29-9 Astemizole -1 down 23756.922 up 388.1561 83881-51-0 C07778

Atorvastatin -1 down 23668.375 up 249.0808 71320-77-9 Beclomethasone -1 down 22843.15 up 249.9873 301-12-2 Bromocriptine -1 down 22824.857 up 724.535 115681-40-8 Buspirone -1 down 22352.531 up 416.1365 102623-18-7 Captopril 3.797065 up 21019.111 up 562.1456 C11646 Carteolol -1 down 20956.943 up 381.3001 82950-64-9 Clofibrate -1 down 20955.807 up 438.1337 741632-17-7 Diltiazem -1 down 20521.209 up 465.3059 52050-17-6 C03108 Disopyramide -1 down 20377.098 up 619.2655 7542-37-2 Etretinate -1 down 20277.986 up 340.0938 1245-15-4 Felodipine -3.045996 down 20214.467 up 190.0734 343-65-7 C00328 Flecainide -1 down 20133.572 up 249.0731 951-77-9 C00881 Flunisolide -1 down 19909.928 up 455.227 139332-94-8 Fluvastatin -1 down 19554.316 up 264.1832 94-24-6 C07526 Hydroxychloroquine -3.9904215 down 19541.045 up 417.1772 66322-66-5 Imipramine -1 down 19519.201 up 442.1041 88378-23-8 Indinavir -1 down 19092.828 up 637.2 64947-41-7 Phenylacetic acid 4.397052 up 18983.967 up 104.0596 1119-16-0 C02373 Tamoxifen -1 down 18923.877 up 289.1464 99473-15-1 Metaproterenol -1 down 18524.145 up 288.1281 4298-15-1 Triamcinolone -1 down 18502.03 up 497.2386 756791-18-1 Methotrimeprazine -1 down 18459.42 up 266.1657 897-06-3 Methylprednisolone -1 down 18393.57 up 329.9027 1861-32-1 Salmeterol -1 down 18086.49 up 358.1239 24560-70-1 Nadolol 52.973804 up 17960.688 up 395.2085 985-13-7 Nalbuphine -1 down 17717.172 up 715.1756 103960-56-1 Nandrolone -1 down 17670.947 up 862.4534 C11967 Nedocromil -1 down 17661.207 up 315.2338 567-03-3 C13713 SILDENAFIL -1 down 17449.043 up 374.1695 58185-99-2

Nifedipine -1 down 17411.344 up 472.1608 106916-15-8 Limonene-1,2-epoxide -1 down 17176.945 up 353.0569 74011-42-0 Stanozolol -3.507238 down 16952.646 up 597.3812 63597-44-4 Olsalazine -1 down 16787.746 up 380.1499 64-86-8 C07592 Oxybutynin -1 down 16525.566 up 598.2662 90650-44-5 Prazosin 3.093966 up 16367.827 up 311.2013 36557-05-8 Prednisone -1 down 16362.818 up 269.1105 2095-20-7 Probucol -1 down 16281.282 up 550.2966 7412-77-3 C01079 Propanolol 267.8809 up 15995.281 up 169.0847 368-16-1 C01152 Pentamidine -1 down 15751.474 up 290.1429 50-33-9 C07440 Phenylbutazone -1 down 15322.978 up 406.2248 122647-31-8 C07753 Terfenadine -1 down 15271.315 up 280.1443 456-59-7 Theobromine -1 down 15033.503 up 247.0576 147-94-4 C02961 Vigabatrin -1 down 14927.525 up 526.2949 150323-38-9 Tetracaine 3.273048 up 14663.064 up 175.059 6133-30-8 C03139 Prilocaine -1 down 14367.212 up 422.2553 67018-85-3 Salicyluric acid -1 down 14130.863 up 351.1713 26844-12-2 Colchicine -1 down 13557.583 up 396.0949 53296-10-9 Hypericin 14.070399 up 13326.34 up 292.2177 54024-22-5 Thioguanine -1 down 13098.452 up 266.0905 35607-33-1 Mifepristone (RU 486) 10.13282 up 12950.806 up 487.2857 475-31-0 NITRENDIPINE 23798.12 up 12799.821 up 335.1879 125-51-9 Ibutilide -1 down 12695.524 up 352.0787 6160-80-1 Cetirizine -1 down 12675.114 up 827.4398 114-07-8 C08031 Mometasone -1 down 12511.769 up 458.2313 401-10-5 C11061 Dolasetron -14.378781 down 12325.686 up 341.1411 15676-16-1 C12653 Diphenoxylate -1 down 12318.266 up 255.9688 22663-37-2 Biperiden -1 down 12294.349 up 482.2314 2753-30-2 Ivermectin B1b -1 down 12017.576 up 457.2785 C11994

Eflornithine -1 down 11936.243 up 450.286 81409-90-7 C08187 Sufentanil -1 down 11898.485 up 640.2476 C04489 hydrocodone -22.669907 down 11855.007 up 385.2496 36505-84-7 C06861 Erythromycin -1 down 11778.44 up 342.1005 49562-28-9 Cycloserine -1 down 11523.699 up 553.445 621-71-6 Cefuroxime axetil -1 down 11005.533 up 775.4539 157141-17-8 Cefpodoxime -1 down 10829.883 up 305.2494 92693-04-4 Diethylstilbestrol diphosphate -6.079131 down 10680.025 up 97.9741 141-46-8 C00266 Cabergoline -1 down 10375.112 up 478.2211 102848-54-4 Diatrizoate -1 down 10195.543 up 526.2512 120398-66-5 Isovaleric acid -1 down 10172.788 up 288.0042 71942-06-8 Jasmonic acid 69.20507 up 9896.281 up 489.2687 09-11-3836 Cucurbitacin A 3.4143527 up 9693.216 up 532.3082 C05468 Cucurbitacin C -1 down 9443.493 up 430.1534 4419-39-0 C06842 Cucurbitacin L -1 down 9423.0205 up 266.0478 70800-61-2 Cucurbitacin P -1 down 9312.191 up 262.0168 637-07-0 C06916 Ipecac (Emetine) -1 down 9274.828 up 569.793 96-83-3 Matricin -1 down 9139.593 up 366.2673 74764-40-2 PICROTIN -1 down 9042.922 up 634.2039 25614-03-3 C06856 Juvenile hormone III -1 down 9035.555 up 287.1773 C13949 Monotropein -1 down 8826.373 up 250.0686 58-63-9 C00294 Valtratum -1 down 8721.356 up 102.0434 68-41-7 C08057 Physcion 8-glucoside -1 down 8333.786 up 473.2526 84713-68-8 DICTAMNINE -1 down 8299.948 up 104.0246 98-96-4 C01956 Aspartame -1 down 8258.371 up 332.0808 85-68-7 C14211 Retinoyl beta-glucuronide -1 down 8184.66 up 306.0346 22594-61-2 2-Methoxy-estradiol-17beta 3-glucuronide -1 down 8095.9014 up 354.0545 20971-53-3 Estrone glucuronide -1 down 8012.129 up 450.1659 2479-90-5 C11133 Dimethyl sulfone -1 down 7937.1 up 464.1116 22888-70-6

S-(p-Azidophenacyl) glutathione -1 down 7916.732 up 320.1297 74011-58-8 Methyl jasmonate -1 down 7664.604 up 310.2423 10418-03-8 C07311 Deoxyloganin tetraacetate -1 down 7610.824 up 355.228 78613-35-1 Loganin pentaacetate -1 down 7495.034 up 302.0861 20244-86-4 Ipecac (Protoemetine) -1 down 7327.6904 up 517.3177 63163-01-9 Gibberellin A36 26.488092 up 7233.3438 up 491.2934 C11995 Taxa-4(20),11(12)-dien-5alpha-acetoxy-10beta-ol -1 down 6938.4004 up 261.0623 05-07-6804 syn-Copalyl diphosphate -1 down 6908.0083 up 228.0879 77-26-9 Avermectin B1b 38.770332 up 6886.1377 up 104.0261 65-85-0 C00180 Megalomicin B -1 down 6750.2803 up 604.2299 114-25-0 C00500 10-Deoxymethymycin 217.61649 up 6682.5254 up 354.2059 43117-32-4 Neomethymycin -1 down 6609.03 up 454.0523 489-50-9 Pikromycin 3.1380804 up 6440.4106 up 280.1825 68-22-4 C05028 DMG-MINO 117.06517 up 6418.811 up 191.0541 3146-50-7 2-amino-8-oxo-9,10-epoxy-decanoic acid -1 down 6302.606 up 330.137 60282-87-3 Phytosphingosine -1 down 5995.849 up 447.326 25486-55-9 C05849 Epothilone B -1 down 5983.037 up 426.1372 105102-22-5 C07816 Nystatin A1 -1 down 5905.086 up 622.2397 630-60-4 C01443 Proansamycin X -1 down 5864.5635 up 510.1059 64544-07-6 C08107 Protorifamycin I -1 down 5800.2896 up 440.236 68844-77-9 C06832 Rifamycin W -1 down 5701.8745 up 567.228 15324-65-9 C03642 OXETHAZAINE -3.2140038 down 5695.2896 up 317.1765 101910-24-1 Sulpiride -1 down 5635.225 up 276.1636 118-10-5 C06528 Zopiclone -1 down 5543.5044 up 801.4668 152432-60-5 Estradiol valerate -1 down 5500.0103 up 258.0702 16232-91-0 C05401 5b-Cholestanol -1 down 5490.743 up 172.0371 10534-44-8 C00944 Hydrocortisone caproate -1 down 5480.224 up 428.186 28782-42-5 5-NITRO-2-PHENYLPROPYLAMINOBENZOIC ACID [NPPB] -1 down 5375.2837 up 294.0322 114991-27-4

Tetrahydrodeoxycorticosterone -3.385017 down 5327.3237 up 454.1637 C11902 9-chloro-10-hydroxy-hexadecanoic acid -14.853671 down 5268.945 up 482.2951 516-90-5 C02592 BENZYLBUTYLPHTHALATE -18.176828 down 5123.805 up 315.1968 113042-18-7 Cimetidine -1 down 5101.9517 up 608.2602 2524-38-1 HYCANTHONE -1 down 5060.9814 up 308.1896 07-12-4360 C06542 GLAFENINE -1 down 5039.3125 up 566.3111 76060-22-5 C03033 VINPOCETINE -1 down 4835.807 up 252.1264 2481-70-1 PROGLUMIDE -1 down 4583.968 up 278.0867 56153-60-7 Sulfaphenazole -1 down 4554.528 up 303.9808 26948-96-9 FLUMEQUINE -1 down 4536.1753 up 369.2638 94421-68-8 N-Acetyl-L-Histidine 2.9883547 up 4516.2876 up 467.2542 86073-06-5 Coproporphyrin II -6.0762634 down 4453.8 up 143.0696 35404-50-3 DELTALINE -1 down 4423.973 up 566.3735 63975-40-6 C05200 FENSPIRIDE -1 down 4403.0576 up 392.2445 27591-69-1 5,6-Dihydrouridine -1 down 4337.9653 up 314.0091 36892-35-0 Pentoxifylline alcohol -1 down 4294.878 up 443.3879 22570-53-2 CARBADOX -1 down 4294.066 up 336.1609 16676-33-8 PSOROMIC ACID -1 down 4218.32 up 466.1719 82219-22-5 Thioridazine 5-sulfoxide -1 down 4199.076 up 422.1929 C09801 Benzyl alcohol -1 down 4189.1646 up 545.2079 26198-65-2 C05554 N-methyl-Aniline -1 down 4098.4106 up 392.1278 82-11-1 2-Hydroxyiminodibenzyl -1 down 4075.2341 up 335.2013 54350-48-0 C06992 1,4-Dideoxy-1,4-Imino-D-Arabinitol -1 down 4046.1902 up 369.3521 516-95-0 C12978 7-Hydroxyetodolac 14.588617 up 3712.625 up 403.2254 17692-51-2 REV-5901 -1 down 3665.238 up 394.2611 73257-80-4 phenylglycol 3-O-sulfate -1 down 3601.4915 up 199.0407 7424-00-2 Bifemelane (M6) -14.158149 down 3517.718 up 342.1844 52-39-1 C01780 AM-580 -1 down 3462.3318 up 318.1083 07-06-6493

Mefenamic acid Metabolite (b-D-Glucopyranuronic acid, 1-[2-[(2,3-dimethylphenyl) amino] benzoate]) -3.9503613 down 3461.476 up 594.344 150378-17-9 C07051 TRIACETIN -1 down 3320.7036 up 290.1365 738-70-5 C01965 Formestane-4-O-glucuronide -1 down 3265.111 up 318.1505 50-49-7 C07049 Oxoproflaxacin -1 down 3217.369 up 324.0921 1113-83-3 C03410 Phenylmethyl methyl ketone 3.0900335 up 3138.0364 up 173.0027 158076-91-6 N2-(ADP-D-Ribosyl)-L-arginine 3.3141265 up 3126.5488 up 402.1873 38753-79-6 N-Didesmethylmifepristone (RU 42848) -13.196924 down 3108.4492 up 337.136 19368-71-9 benzonatate (2,5,8,11,14,17,20,23,26- Nonaoxaoctacosan-28-yl p-(butylamino)-benzoate -1 down 3050.26 up 360.1371 84845-75-0 C07713 Hydroxythiopental -1 down 3020.5938 up 401.1956 52-21-1 1,2-Propanediol, 3-[[2-(2-methoxyphenoxy) ethyl] amino] -1 down 3007.955 up 358.155 82009-34-5 C01675 4-Hydroxypropranolol -1 down 2986.4705 up 378.1362 3105-97-3 D00541 Ergoline-1-carboxaldehyde, 8-(hydroxymethyl)-10- methoxy-6-methyl-, (8b)- -1 down 2804.2766 up 68.0239 64-17-5 C00469 epsilon-Caprolactam -1 down 2708.5571 up 338.1072 52208-24-9 8-Azaspiro [4.5] decane-8-butanoic acid, 7,9-dioxo (buspirone metabolite) -1 down 2656.3752 up 338.2369 86197-47-9 Coenzyme Q6 -1 down 2555.923 up 195.0464 366-77-8 2H-Indol-2-one, 4-[2-(dipropylamino) ethyl]-1,3- dihydro-7-hydroxy- glucuronide -1 down 2515.7983 up 222.0511 102-76-1 Troglitazone sulfate -12.916357 down 2502.713 up 314.1195 74772-77-3 cyclohexylammonium -1 down 2480.5354 up 283.1935 22259-21-8 4-(2-Hydroxy-3-isopropylaminoproxy)-benzyloxy acetic acid -1 down 2391.21 up 358.1172 85677-95-8 Desmosine -1 down 2377.3953 up 269.1785 90293-01-9 Vitamin K2 -1 down 2352.0225 up 456.2153 915-30-0 C07872 14-Hydroxy-6-O-methylerythromycin A -1 down 2312.3318 up 354.2183 302-23-8 1-Hexadecyl-2-O-methyl-glycerol -1 down 2306.5796 up 494.2153 36011-19-5 4-Hydroxypenbutolol glucuronide -3.7605329 down 2263.455 up 308.0674 2204-59-3

1-Methylhypoxanthine -1 down 2224.5781 up 496.1805 140695-49-4 3-Hydroxy-N-glycyl-2,6-xylidine (3- Hydroxyglycinexylidide) -1 down 2131.803 up 506.2554 C12154 FENDILINE -1 down 2082.9949 up 152.0438 56-17-7 CHLORPROTHIXENE 125427.555 up 1984.7709 up 129.0787 68506-86-5 C07500 CARYLOPHYLLENE OXIDE -1 down 1913.455 up 367.2638 15262-86-9 1,4-Benzenediol, 2,6-bis(1-methylethyl)-, 4- (hydrogen sulfate) -1 down 1890.1787 up 373.239 143-62-4 Northiadene -1 down 1765.0856 up 472.1606 97729-57-2 Cerebroside A -1 down 1735.1162 up 303.1232 125-29-1 C08024 o-Hydroxyfinasteride -1 down 1686.3245 up 504.1561 62996-74-1 C02079 o-Monocarboxylfinasteride -3.3384836 down 1636.0559 up 385.2015 66-28-4 RO 40-5966 (Methylmibefradil Metabolite) -1 down 1583.7223 up 324.0119 36846-99-8 Ofloxacin-N-oxide -339.46967 down 1330.3606 up 246.1318 34522-32-2 C04137 PERUVOSIDE -1 down 1328.055 up 338.0801 14736-62-0 Dihydroxyaltramine 45423.625 up 1072.4773 up 164.0473 111-16-0 C02656 Perindopril glucuronide -7735.5737 down 1064.7072 up 246.1366 40053-65-4 3-O-Methylisoproterenol 1.1720163 up 1021.4432 up 333.1718 102121-60-8 6'-Exomethylenesimvastatin -26.751593 down 951.0198 up 179.0691 01-02-2497 p-Acetaminobenzaldehyde -7.3836617 down 927.2505 up 168.0238 13205-48-6 4-heptanone -133.52173 down 784.3566 up 248.0536 127-69-5 PROPIOMAZINE 4830.7627 up 778.3611 up 141.0783 52320-67-9 1-Octadecanamine -102.633125 down 643.2123 up 314.0826 113-59-7 QUERCETIN TETRAMETHYL (5,7,3',4') ETHER -160.17677 down 526.30835 up 303.1611 99473-14-0 PIPENZOLATE -16.367792 down 418.12442 up 273.0823 68693-11-8 16beta-Hydroxystanozolol -8419.893 down 412.23456 up 204.0892 20333-85-1 Cholesterol sulfate -728.8762 down 156.95483 up 129.0574 100-61-8 Dextromethorphan -445.89523 down 95.61661 up 498.2878 14605-22-2 7-Hydroxyondansetron sulfate 36121.56 up 76.21045 up 424.1663 55028-72-3

Sulfisoxazole -1402.4165 down 54.61535 up 189.0739 73141-47-6 4-Ketoretinoic acid glucuronide 7711.6084 up 53.06265 up 243.0715 42835-25-6 D02302 Dihydroceramide C2 -174.34346 down 40.27575 up 161.0471 83-67-0 C07480 Penicilloic G acid -561.50604 down 36.538902 up 117.0577 105-60-2 Meperidine N-oxide -1010.72876 down 35.65929 up 238.0743 2504-22-5 Methylthiobenzoic acid -703.2586 down 32.56509 up 298.096 4376-20-9 N-Isopropylterephthalaldehydamide -14237.932 down 29.77913 up 143.0731 2627-86-3 C02455 Acetyl-farnesyl-cysteine 28327.17 up 29.034983 up 131.0692 6020-87-7 C00300 farnesylthioacetic acid 21607.582 up 28.039415 up 151.063 26687-79-6 Troglitazone quinone -124.16755 down 24.129238 up 431.2698 152405-02-2 Trimethobenzamide -1067.5134 down 19.261303 up 322.1103 99210-81-8 17alpha,20beta-Hydroxyprogesterone sulfate -3215.6147 down 15.182308 up 237.0945 C12027 AGGC -192679.22 down 12.476554 up 187.0628 32387-22-7 CANDESARTAN CILEXTIL -1982.5011 down 11.5838995 up 177.0427 487-54-7 C07588 Sodium tetradecyl sulfate -21617.74 down 11.106706 up 145.0525 77-67-8 8-hydroxymianserin glucuronide 29114.508 up 9.356015 up 166.0198 154-42-7 C07648 3-Hydroxycapric acid 19626.498 up 4.7920713 up 189.0638 17686-38-3 1-Hexadecylamine 24434.445 up 3.3693373 up 159.0102 6339-54-4 Digitoxigenin -9451.361 down 2.859068 up 303.1088 1154-09-2 9-Hydroxyrisperidone -4878.513 down 2.3575892 up 260.1224 99614-14-9 N-Desmethylmibefradil -16721.404 down 1.6374724 up 446.1233 C10384 Tauroursodeoxycholic acid 26097.28 up 1.5168729 up 189.0422 21997-21-7 TODRALAZINE 382657.56 up 1.411076 up 150.0543 1125-39-9 DERRUSNIN 78607.77 up 1.3448719 up 138.0426 36117-26-7 Pregnanolone sulfate -49716.88 down 1.2766227 up 180.064 543-38-4 C00308 Diphenylmethylphosphine -315548.4 down 1.2446866 up 90.0468 100-51-6 2-Methyl-3-ketovaleric acid -24421.672 down 1.2204576 up 141.0573 2591-98-2 C00637 N-depyridomethyl-Indinavir 152905.06 up 1.1504027 up 270.0851 23885-72-5 Tropicamide 50800.766 up -1.0201263 down 519.2288 144917-76-0

Hydroxysalmeterol 195592.02 up -1.0970556 down 151.0088 50-44-2 C02380 Tacrolimus metabolite M-IV 6921.355 up -1.1435556 down 390.1195 08-05-7776 flurandrenolide -117244.516 down -1.3984767 down 390.1123 C09788 Testosterone isocaproate -67897.16 down -1.4718965 down 412.1968 138949-80-1 L-Glutamic acid n-butyl ester -165496.92 down -1.4892215 down 176.0944 112606-87-8 3-Hydroxymorphinan -116711.89 down -1.8543481 down 443.2268 54763-91-6 Didesmethyltacrolimus -1189968 down -1.8738505 down 241.1091 61-68-7 C02168 1-Propene, 1,3,3,3-tetrafluoro-2-(fluoromethoxy)-1- methoxy-, (Z)- (Compound C) 462.86734 up -1.8876181 down 83.0372 22059-21-8 1,2-Benzenediol, 4-[[4-(4-fluorophenyl)-3- piperidinyl] methoxy]-, (3S-trans)- -24566.066 down -2.3141978 down 412.0951 24340-62-3 Indinavir-N-oxide -55634.086 down -2.485179 down 324.1201 18783-43-2 2,2-dimethyl-4-pentenoic acid 7.47E+07 up -3.5442994 down 301.2985 764-22-7 C00836 Digitoxigenin bisdigitoxoside 2.55E+07 up -3.5442994 down 554.046 73384-59-5 C06683 Nalbuphone 3814659.8 up -3.5442994 down 317.2933 554-62-1 C12144 N, N- Didemethyldiphenhydramine 1517085.8 up -3.5442994 down 342.2994 13031-64-6 Glutarylglycine 710739.3 up -3.5442994 down 366.2118 135304-07-3 METERGOLINE 594340.9 up -3.5442994 down 143.0732 526-55-6 C00955 2-Amino-5-nitrobenzophenone 487835.16 up -3.5442994 down 151.0631 65-23-6 C00314 CYCLOPIAZONIC ACID 402223.44 up -3.5442994 down 259.1785 4261-76-1 2-(diethylamino)-4'-hydroxy-Propiophenone 286723.6 up -3.5442994 down 241.2771 143-27-1 a-[1-(diethylamino)ethyl]-p-hydroxy-Benzyl alcohol 244425.38 up -3.5442994 down 350.2417 24607-09-8 4-Methylumbelliferyl heptanoate 171672.72 up -3.5442994 down 199.0666 62571-86-2 C06867 DACTHAL 164737.25 up -3.5442994 down 321.1784 3947-65-7 C01441 7-Desmethylpapaverine 134696.45 up -3.5442994 down 226.1931 2507-55-3 Dextrorphan sulfate 104086.07 up -3.5442994 down 179.0581 59-92-7 C00355 25-Azacholesterol 103743.44 up -3.5442994 down 294.1213 22839-47-0 C11045 Arachidonoyl dopamine 89772.22 up -3.5442994 down 348.2158 125590-76-3 3-hydroxy-phenylglycol 84410.41 up -3.5442994 down 213.2458 2016-42-4

Tetradecylamine 70525.52 up -3.5442994 down 279.1469 109791-19-7 7-Methylguanosine 68205.75 up -3.5442994 down 176.0206 492-11-5 4-aminohippurate 49026.43 up -3.5442994 down 280.0977 07-08-5053 2-Hydroxytrimipramine 48756.375 up -3.5442994 down 485.4228 104404-17-3 C00195 2-Benzimidazolinone, 1-(4-piperidyl)- 41620.01 up -3.5442994 down 336.2054 37517-30-9 C06803 Norpromazine 38215.2 up -3.5442994 down 238.0832 90-50-6 N1-(2-Hydroxyethyl) flurazepam 33465.85 up -3.5442994 down 344.1371 57998-68-2 1-(2-Pyrimidyl) piperazine 22726.74 up -3.5442994 down 114.0465 83-33-0 DEOXYGEDUNIN 21629.59 up -3.5442994 down 309.1937 42200-33-9 C07249 Aminofurantoin 19880.166 up -3.5442994 down 185.105 152726-66-4 DERRUSTONE 16705.043 up -3.5442994 down 383.1073 4542-23-8 1-Aminocyclopropane-1-carboxylic acid 15974.687 up -3.5442994 down 395.0353 66340-28-1 Naloxone-3-glucuronide 14515.08 up -3.5442994 down 256.1102 26213-95-6 Pentazocine cis- alcohol 9837.41 up -3.5442994 down 140.1064 664-90-6 Azoprocarbazine 3920.7073 up -3.5442994 down 263.1533 71186-68-0 ZEORIN -479001.56 down -3.778182 down 73.0501 352-92-1 C02229 3-Deoxy-D-glycero-D-galacto-2-nonulosonic acid -163898.7 down -5.4829063 down 331.2284 467-83-4 p-Chlorobenzenesulfonylurea 209327.4 up -11.614694 down 227.2614 2570-26-5 5-Phenylvaleric acid 20591.912 up -12.955104 down 207.1261 1212-03-9 SILYBIN 1743.929 up -14.583608 down 258.1076 56392-15-5 PROPARGITE 3889.7708 up -15.0000925 down 179.0808 3416-24-8 C00329 Glucoheptonic acid -1293676.4 down -16.450071 down 562.4187 11032-49-8 Chloramphenicol alcohol -24612.635 down -17.192623 down 285.1351 101901-07-9 Ubiquinone 8 9826.608 up -17.406996 down 414.2047 73603-90-4 Leupeptin -57395.273 down -18.717533 down 376.1684 124-94-7 C07158 ICHTHYNONE -20151.615 down -26.394232 down 330.1998 71441-28-6 isopropamide -796686.7 down -32.84152 down 510.2787 915-35-5 5a,7a-Dihydroxy-11-ketotetranorprostanoic acid -25692.816 down -40.03195 down 472.2484 59132-31-9 Ethynylestradiol 3-sulfate -14797.154 down -55.56217 down 380.0732 69-79-4 C00208

AVOCADENE ACETATE -88531 down -79.016235 down 241.1098 32459-45-3 Vanillactic acid -26375.688 down -82.07954 down 264.0266 23351-51-1 Dihydroisolysergic acid II -7861.282 down -93.07688 down 860.4918 70209-81-3 C07970 5-Methoxytryptophan 1425.9464 up -93.410706 down 260.1235 56523-61-6 2-Hydroxymyristic acid 8620.153 up -118.369385 down 202.0454 50-99-7 C00031 Clobetasol propionate 183.46567 up -238.53198 down 223.1196 10461-27-5 KHIVORIN 24.663502 up -253.96843 down 218.0185 59-23-4 C00124 n-Pentadecylamine -50704.883 down -303.7845 down 613.7703 117-96-4 C08216 LASALOCID -15822.907 down -323.7616 down 452.1536 5939-37-7 1-Benzyloxycarbonylaminophenethyl chloromethyl ketone -411185.88 down -379.61063 down 102.047 2628-17-3 C05627 Heteropeucenin, methyl ether -26896.783 down -398.40765 down 245.141 18259-41-1 5-amino-1-[3,4-dihydroxy-5-(hydroxymethyl) oxolan-2-yl] imidazole-4-carboxamide 59.849762 up -489.59106 down 145.0528 122-85-0 ANGOLENSIC ACID, METHYL ESTER 1803.1781 up -673.2794 down 106.0417 623-05-2 N-Nitroso-N-morpholinoaminoacetonitrile -113089.66 down -765.4994 down 383.2255 104004-92-4 Indoramin -101013.69 down -938.991 down 470.2069 21963-95-1 resorcinol sulfoxide 166.11456 up -1260.0048 down 117.0576 55576-55-1 C02558 N-Fluorenylacetamide -22546.996 down -1310.5607 down 420.2302 121624-18-8 GEDUNIN -81.7782 down -3100.9868 down 298.176 71963-77-4 Tilorone -5422538 down -3687.5986 down 270.0548 14679-73-3 5-(3,4-Dihydroxy-1,5-cyclohexadien-1-yl)-5- phenylhydantoin -11032.295 down -4225.7217 down 136.0384 68-94-0 C00262 Diphenoxylic acid(DPA) -15699.653 down -4341.8325 down 658.1669 53915-13-2 3-Hydroxyphenytoin -22956.305 down -5259.744 down 219.1378 2235-59-8 Oleamide -58386.004 down -5424.1196 down 274.1013 75001-77-3 OXDEMETONMETHYL -19070.287 down -5764.1846 down 358.1947 50-50-0 Hydroxyprogesterone acetate -65228.316 down -6737.985 down 360.0802 4697-36-3 Harderoporphyrin 1.0062717 up -7161.384 down 180.0639 87-89-8 C00137 Doxapram -102865.125 down -8877.444 down 654.2925 C12247

D-Glucoheptose -9283.409 down -8948.629 down 626.2611 545-57-3 L-Glutamic acid, 4-hydroxy- -8885.329 down -9673.322 down 259.083 80288-49-9 INDOPROFEN -11019.86 down -10520.935 down 255.1249 466-80-8 C06531 deschlorobenzoyl Indomethacin -31898.2 down -11966.423 down 448.1257 60-54-8 C06570 3-O-Methylrimiterol -134949.39 down -12602.046 down 360.1371 100-33-4 C07420 Norpropoxyphene -16013.954 down -15450.605 down 370.2178 10540-29-1 C07108 N-Acetylprocainamide -77651.805 down -16693.893 down 231.0399 636-58-8 C00669 2-Propylglutaric acid -168411.53 down -17680.447 down 125.0838 23256-39-5 C03078 amitraz -29576.297 down -17992.346 down 410.1815 138-56-7 THIAMYLAL -5175.999 down -18345.291 down 244.0039 57101-48-1 Diethylstilbestrol monosulfate -6.430729 down -19547.66 down 155.0341 155909-30-1 C04236 3-Methylsuberic acid -5173.28 down -20868.482 down 318.1635 135784-48-4 3-Hydroxydodecanedioic acid -6516.006 down -23094.676 down 206.0248 7259-44-1 3,4-bis(methylene)-Hexanedioic acid -25725.43 down -23222.148 down 634.3726 16479-50-8 5C-aglycone -6907.0586 down -24480.684 down 438.1834 03-03-3385 C07005 10,11-Dihydro-dihydroxy-carbamazepine -7256.782 down -25720.209 down 251.0817 35079-97-1 Ergoline-8-methanol, 10-methoxy-6-methyl-, (8b)- -29060.15 down -29483.945 down 284.1611 71939-50-9 9-dodecen-1-ol -8666.329 down -30716.066 down 739.4499 527-75-3 C06653 CYCLOCREATINE -43872.26 down -34466.484 down 502.2953 5352-63-6 5-(3,4-Dihydroxy-1,5-cyclohexadien-1-yl)-5- ethylbarbituric acid -9726.175 down -34472.477 down 394.0701 3820-67-5 D01351 5-(3,4-Dihydroxyphenyl)-5-ethylbarbituric acid -9889.284 down -35050.582 down 188.0079 99-24-1 Dextromoramide -10023.725 down -35527.082 down 694.187 64364-50-7 C04886 21-Hydroxydydrogesterone -10643.271 down -37722.94 down 478.1769 139755-83-2 C07259 CYTOCHALASIN E -10686.134 down -37874.86 down 564.3061 C08795 4-Imidazolone-5-propionic acid -3974.3677 down -42104.105 down 450.1727 63800-01-1 1-Hydroxytetrahydrocannabinol -12138.044 down -43020.863 down 266.1417 1508-75-4 B-(4-Fluorobenzoyl) propionic acid -213.06473 down -43692.07 down 282.099 107254-86-4 C13705 Phosphoribosylglycinamide -322.3773 down -45241.457 down 166.0475 17812-24-7 C01685

3-hydroxychlorpropamide -13364.2295 down -47366.832 down 385.1959 56030-54-7 C08022 8alpha-3beta-hydroxy-estra-1,3,5(10)-trien-17-one -200504.83 down -48277.105 down 360.1371 74011-56-6 Benzophenone -13762.811 down -48779.52 down 503.0758 C07606 6beta-Hydroxytriamcinolone acetonide -13873.334 down -49171.25 down 357.0593 08-11-7299 Deacetylspironolactone -14243.74 down -50484.08 down 262.1202 87549-34-6 7alpha-(Thiomethyl)spironolactone sulfone -5032.2754 down -52262.09 down 292.0962 21416-53-5 C09528 2H-Indol-2-one, 1,3-dihydro-4-[2-hydroxy-3-[(1- methylethyl) amino] propoxy]- -15056.039 down -53363.11 down 206.1659 1139-30-6 Glibornuride M6b -15404.315 down -54597.508 down 658.2426 09-03-3082 3-Methyl-3Z-Pentenoic Acid -4052.261 down -56203.22 down 260.0436 54927-81-0 2-Methylhippuric acid -16196.491 down -57405.215 down 623.3069 C12176 ESTRADIOL ACETATE -16458.879 down -58335.195 down 174.0883 32806-62-5 Dinorpropoxyphenecarbinol -16693.883 down -59168.117 down 331.0637 36322-90-4 C01608 Ketodoxapram -16840.73 down -59688.594 down 391.2516 65646-68-6 2-Pyrrolidinone, 4-(2-morpholinoethyl)-3,3- diphenyl- -16915.953 down -59955.2 down 162.0313 4607-41-4 L-Glutamic acid dibutyl ester -18588.775 down -65884.19 down 300.1246 6106-81-6 (±)-Desethylhydroxychloroquine -19096.54 down -67683.85 down 338.0435 70643-28-6 p-Hydroxypropoxyphene -19122.7 down -67776.62 down 216.0091 101911-70-0 fenbendazole -2.6443236 down -75679.695 down 464.3485 863-39-8 alpha-Phenylcyclohexylglycolic acid -22334.32 down -79159.57 down 170.1313 14292-26-3 Phthalic acid Mono-2-ethylhexyl Ester -23028.758 down -81620.87 down 166.1712 35148-18-6 2-(N-morpholino) ethanesulfonic acid -1605.9634 down -82365.58 down 516.312 23288-49-5 C07373 Succinoadenosine -23316.502 down -82640.664 down 203.0501 57683-62-2 cyclandelate -10.597192 down -88023.78 down 166.0625 C05594 m-Hydroxyphenylpyruvic acid -1470.354 down -88237.36 down 610.2332 5522-66-7 Dipipanone -1605.3224 down -88478.58 down 580.2338 134523-00-5 C06834 carbenicillin -25001.48 down -88612.734 down 262.0941 15763-06-1 C02494 alpha-Ketopantoic acid -326.73892 down -92801.81 down 452.2199 2629-14-3

CHAULMOSULFONE -26286.432 down -93166.92 down 471.1718 2311-81-1 C00664 2-Amino-3-methyl-1-butanol -27421.94 down -97191.5 down 366.275 68002-72-2 Cholylglycine -27612.75 down -97867.92 down 594.3544 25999-31-9 COLCHICEINE -27682.895 down -98116.41 down 404.1629 482-53-1 1-Naphthylmethanol -2099.831 down -99636.805 down 525.2784 11003-57-9 BERBAMINE -29355.125 down -104043.29 down 198.053 55-10-7 C05584 OSAJIN -2004.4812 down -112536.47 down 174.0086 20150-19-0 FUMARPROTOCETRARIC ACID -20.080172 down -113525.875 down 223.0488 1775-95-7 LEUCOPTERIN -10569.13 down -116058.41 down 346.1159 21829-25-4 C07266 Fenofibrate -33288.465 down -117984.36 down 372.1185 91488-19-6 ESTRADIOL BENZOATE -8824.979 down -120954.24 down 332.1426 2312-35-8 N-acetyl-4-aminosalicylic acid -34467.33 down -122162.445 down 638.2976 C12246 Hydroxyibuprofen -35421.32 down -125543.85 down 359.1277 117678-38-3 PIPEMIDIC ACID -37499.83 down -132910.53 down 925.5061 34786-70-4 C12155 Promazine N-oxide sulfoxide -37751.33 down -133801.92 down 352.075 34210-88-3 PREDNISOLONE ACETATE -171.90025 down -137105.78 down 282.1819 25593-72-0 C02567 LOBARIC ACID -38974.664 down -138137.78 down 956.518 C11986 DUARTIN (-) -39706.516 down -140731.78 down 186.0885 20980-22-7 2-Methylbutyrylglycine -39905.258 down -141436.1 down 497.2903 C08802 Levonorgestrel oxime -953.0273 down -143186.95 down 418.2151 1524-88-5 2-Phenylaminoadenosine -40977.766 down -145237.47 down 362.1732 C11862 6b-Hydroxycortisol -41589.184 down -147404.61 down 358.1297 18172-33-3 3,5-Diiodothyronine -44169.363 down -156549.56 down 434.1078 42399-41-7 C06958 Digoxigenin monodigitoxoside -44216.426 down -156716.27 down 152.1203 1195-92-2 C07271 Diethylstilbestrol diglucuronide -44448.17 down -157537.64 down 340.1059 7323-86-6 Desogestrel -44882.727 down -159077.81 down 315.1722 33089-61-1 OXONITINE -47165.363 down -167168.17 down 442.2708 C13422 Pentazocine glucuronide -48476.715 down -171816 down 113.9543 67-71-0 C11142 2-Pyridylacetaldehyde -49298.766 down -174729.6 down 168.0417 451-13-8 C00544

Cystathionine sulfoxide -49454.95 down -175283.03 down 105.0788 111-42-2 C06772 p-Hydroxytiaprofenic acid -50.210148 down -176238.06 down 166.0261 79427-92-2 2-Thiopheneacetic acid, 5-(hydroxyphenylmethyl)- alpha-methyl- -50323.78 down -178362.67 down 374.0915 13057-98-2 Cloprostenol -50403.383 down -178644.69 down 464.163 144598-75-4 Dimethylprotoporphyrin IX dimethyl ester -51347.535 down -181990.92 down 498.1468 67-78-7 1-(5-Hydroxy-2-pyrimidinyl) piperazine -3253.238 down -197536.36 down 530.2895 1182-87-2 SECURININE -57806.418 down -204883.39 down 466.193 25122-46-7 (2-Chlorophenyl) diphenylmethane -58097.562 down -205915.3 down 194.0577 2475-56-1 Cystamine -59557.152 down -211088.52 down 324.1686 56275-39-9 C00390 Phenoperidine -10213.485 down -216520.2 down 701.2014 33014-54-9 C01221 2-Hydroxy-3-(4-methoxyethylphenoxy)-propanoic acid -1.2026542 down -224392.27 down 193.1095 586-06-1 C07144 gamma glutamyl ornithine -63837.527 down -226259.17 down 117.0337 103-82-2 C07086 Formestane -66105.89 down -234299.08 down 673.232 741665-60-1 p-Hydroxyclonidine -66165.086 down -234508.88 down 921.6533 77538-38-6 C06126 Dehydronorketamine -66942.1 down -237262.86 down 519.2653 59005-70-8 m-Chlorohippuric acid -67070.47 down -237717.83 down 420.1294 85677-93-6 DIAZIQUONE -68365.73 down -242308.6 down 561.2193 C12011 Idebenone Metabolite (Benzenehexanoic acid, 2,5- dihydroxy-3,4-dimethoxy-6-methyl-) -68542.29 down -242934.4 down 182.1666 143-07-7 C02679 Idebenone Metabolite (QS-10) -68713.87 down -243542.52 down 90.0317 96-26-4 C00184 ALBIZZIINE -69973.84 down -248008.27 down 624.9193 58337-43-2 C03483 Taurallocholic acid -71678.15 down -254048.83 down 140.0626 4780-79-4 Chenodeoxycholic acid sulfate -74600.28 down -264405.75 down 134.0363 156-38-7 C00642 7-Hydroxymethotrexate -75312.39 down -266929.7 down 270.124 18319-92-1 MEPHENESIN -76113.17 down -269767.88 down 215.1305 77-17-8 Gestodene -77287.805 down -273931.12 down 254.0942 34927-45-2 ether -77666.28 down -275272.56 down 85.0528 1118-68-9 C01026 Ubiquinone (Q2) -81634.68 down -289337.75 down 573.3068 C08793

2-Methylcitric acid -7414.2637 down -307617.03 down 263.0934 31842-01-0 (-)-Scopolamine N-oxide hydrobromide -195.23836 down -312886 down 584.217 553-12-8 C02191 Chimyl alcohol -30163.855 down -315749.56 down 199.045 3646-68-2 C03752 4-Methylumbelliferyl beta-D-glucuronide -94009.65 down -333198.34 down 200.0469 55745-85-2 4-Ethylbenzoic acid -97059.37 down -344007.47 down 352.2935 111188-59-1 Capric acid triglyceride -6918.5464 down -346767.75 down 203.1316 18259-39-7 p-Methylolphenol -98455.29 down -348955.03 down 59.0734 75-50-3 C00565 FLUOROACETATE -100527.945 down -356301.16 down 283.1687 566-48-3 Linolenoyl lysolecithin -101775.09 down -360721.4 down 247.1574 6452-71-7 Arachidonyl lysolecithin -131.37485 down -369939.8 down 396.1907 53-35-0 I-Methyl-4-nitro-5-thio-imidazole -9389.55 down -376373.8 down 385.1515 7336-33-6 PHORBOL MYRISTATE ACETATE -107107.234 down -379620.1 down 132.0057 87-69-4 C00898 Pyridinoline -109056.66 down -386529.44 down 97.9766 7664-38-2 C00009 Benzenemethanol, 2-(2-aminopropoxy)-3-methyl- -114297.85 down -405105.8 down 454.1777 3869-32-7 APHYLLIC ACID -117376.97 down -416019.12 down 294.1851 139-88-8 Oxprenolol -2410.0112 down -417837 down 265.1919 642-67-1 Morphine 3,6-diglucuronide -120822.87 down -428232.44 down 366.1362 477-27-0 4-Hydroxyphenylretinamide -121088.805 down -429174.97 down 204.0808 27215-65-2 Desmethylloperamide -121942.99 down -432202.47 down 386.1294 40724-45-6 Clonidine Metabolite IV -130035.36 down -460884.25 down 257.1024 5610-40-2 STROPHANTHIDIN -139410.69 down -494113.22 down 336.1919 84978-42-7 Propranolol glucuronide -141465.83 down -501397.25 down 228.1353 34574-69-1 Desacetylcefotaxime -144151.28 down -510915.3 down 455.2333 C03577 Desmethylranitidine -9580.47 down -525057.25 down 356.1379 606-06-4 DL-2-Aminooctanoic acid -149771.33 down -530834.44 down 237.0654 20662-53-7 COLFORSIN -151291.97 down -536224.06 down 103.0424 54765-14-9 Norverapamil -154221.05 down -546605.56 down 399.1574 94388-32-6 Taurochenodeoxycholate-3-sulfate -154397.31 down -547230.3 down 110.1094 124-13-0 C01545 PERHEXILINE -4658.8975 down -548462.3 down 336.0951 52305-04-1

Met-Arg-Phe-Ala acetate salt -40766.133 down -554168.7 down 269.308 124-30-1 TRIAMCINOLONE DIACETATE -160409.38 down -568538.9 down 209.1192 17349-94-9 1-heptadecanoyl-rac-glycerol -2.8774898 down -576888.06 down 222.1257 51146-55-5 Ethenodeoxyadenosine -163403.89 down -579152.3 down 167.013 700-06-1 MODAFINIL -165506.55 down -586604.75 down 602.3558 104-31-4 Ursodeoxycholic acid 3-sulfate -166390.72 down -589738.5 down 200.1047 73141-46-5 INDOLE-3-CARBINOL -166619.66 down -590549.94 down 306.0397 28129-90-0 4-Hydroxyclobazam -171185.89 down -606734.06 down 268.1564 35121-60-9 5-Hydroxysulfadiazine -5588.7905 down -607809.9 down 296.0737 526-08-9 D01954 3a-OH Desogestrel -125.60522 down -641165.2 down 211.0448 1188-37-0 C00624 Barbituric acid, 5-ethyl-5-(2-hydroxyethyl)- -181352.52 down -642767.6 down 88.0163 473-81-4 C00258 4-Hydroxyoxprenolol -42971.04 down -669129.94 down 164.083 59-47-2 Moclobemide -194798.73 down -690425 down 142.1099 7622-29-9 C02728 TTNPB -199452.56 down -706919.6 down 498.2122 91411-76-6 Dihydroartemisinin -3844.3032 down -711420 down 276.1708 32795-44-1 2H-1-Benzopyran-6-acetic acid, 7-hydroxy-8- methoxy-2-oxo- -1230.9109 down -726621.4 down 222.0567 1486-28-8 Artemether -205718.56 down -729128.2 down 257.102 105920-65-8 Norharman -206622.4 down -732331.7 down 178.0627 93-40-3 3-Hydroxysebacic acid -753.3371 down -736014.25 down 608.2175 C04144 3-Hydroxysuberic acid -61007.137 down -748332.06 down 338.2799 6145-69-3 3-Hydroxytetradecanedioic acid -213466.69 down -756589.9 down 326.1478 93128-32-6 6-Ketoestriol -215618.08 down -764215.06 down 278.2595 C01554 DL-PDMP -216742.73 down -768201.1 down 61.0526 141-43-5 C00189 Desmethylcolchicine -223716 down -792916.5 down 96.0939 123-19-3 6b,11b,16a,17a,21-Pentahydroxypregna-1,4-diene- 3,20-dione 16,17-acetonide -14533.044 down -814218 down 270.1975 4075-13-2 C05295 4-Oxo-norfloxacin -229938.47 down -814970.75 down 192.1162 6894-38-8 C08491 N-Acetylnorfloxacin -236207.19 down -837189 down 158.0572 10593-78-9 C05650

ENOXACIN -2652.7795 down -878804.06 down 356.1787 38753-76-3 Idebenone Metabolite (Benzenedecanoic acid, 2- hydroxy-3,4-dimethoxy-6-methyl-5-(sulfooxy)-) 1.6198239 up -888377.1 down 234.125 4335-77-7 Neu5Acalpha2-6GalNAcalpha-Thr -4780.659 down -890120.6 down 137.0587 71-00-1 C00135 p-CHLOROPHENYLALANINE -254328.75 down -901417.25 down 907.6373 151122-71-3 C06125 BEPRIDIL -265848.47 down -942246.56 down 157.0885 78682-61-8 Ciglitazone -267094.2 down -946661.75 down 308.1133 2535-20-8 C04332 Desethylenenorfloxacin -63813.1 down -986189.06 down 398.2121 1477-67-4 Paromomycin -284671.1 down -1008959.6 down 102.0681 503-74-2 C08262 Idebenone Metabolite (beta-D- Glucopyranosiduronic acid, 4-hydroxy-3-(10- hydroxydecyl)-5,6-dimethoxy- -300105.53 down -1063663.9 down 169.0884 92-67-1 Diethyl Oxalpropionate -3163.0798 down -1084110.5 down 370.0919 69049-73-6 C07255 Epirubicinol -24191.777 down -1084417.2 down 482.2384 112160-84-6 Naltrexone-3-glucuronide -28070.79 down -1095740.4 down 326.0703 38150-27-5 Normeperidine -316842.22 down -1122983.8 down 318.1859 90-69-7 butalbital -318798.16 down -1129916.1 down 250.0733 30074-03-4 Ethosuximide -319851.47 down -1133649.4 down 185.0297 3157-41-3 Amorolfine -322684.03 down -1143688.9 down 140.0332 97-59-6 C01551 N-Acetyltranylcypromine -325516.75 down -1153728.8 down 188.1045 34284-35-0 3,4-dihydroxymandelate -86548.56 down -1158701.4 down 88.0528 513-86-0 C00810 Furafylline -356932.44 down -1265075.5 down 411.2555 84371-65-3 C07652 albendazole (V) -376006.75 down -1332680.5 down 275.1519 10476-53-6 beta-TOXICAROL -395121.3 down -1400428.2 down 192.0807 10064-85-4 Phenylbutazone glucuronide -53.012478 down -1565971.6 down 248.176 C09694 1,2-Didecanoyl-glycerol (10:0) -135935.86 down -1582505 down 310.1178 C09499 1-Indanone -452856.47 down -1605059 down 132.0573 619-64-7 Flecainide meta-O-dealkylated -128.54709 down -1698870.1 down 148.0154 100-21-0 C06337 ACETYL TYROSINE ETHYL ESTER -481870.62 down -1707893.9 down 112.0521 14925-93-0

Idebenone Metabolite (QS-8) -496685.22 down -1760401.1 down 132.0784 20312-37-2 C03264 Fluvoxamine acid -507199.66 down -1797667.4 down 146.0574 2438-80-4 C01019 20alpha-Dihydroprogesterone glucuronide -514834.47 down -1824727.5 down 96.0576 41653-93-4 Idebenone Metabolite (Benzenedecanoic acid, 2,5- dihydroxy-3,4-dimethoxy-6-methyl-) -525149.6 down -1861287.4 down 343.2024 05-09-3737 C06965 Dehydronimodipine -8938.933 down -1956196.8 down 428.0785 522-40-7 C08145 3,5-Pyridinedicarboxylic acid, 1,4-dihydro-2,6- dimethyl-4-(3-nitrophenyl)-, 2-hydroxyethyl methyl es -561485.2 down -1990071.6 down 244.1323 13147-07-4 Penbutolol glucuronide -571777.94 down -2026552.1 down 318.2911 66719-58-2 C02198 Dehydroisocoproporphyrinogen -600110.25 down -2126970.5 down 285.1224 51940-44-4 Dopexamine -7603.593 down -2138457.5 down 253.1818 125-71-3 Trihydroxycoprostanoic acid -615904.6 down -2182950.5 down 128.0471 470-30-4 Betaxolol(deaminated) -154275.08 down -2324192.8 down 370.0915 83526-33-4 Loxoprofen Metabolite (b-D-Glucopyranuronic acid, 1-[a-methyl-4-[(2-oxocyclopentyl) methyl] benzeneace -32756.586 down -2334987.8 down 991.732 77538-38-6 C06126 ANDROSTA-1,4-DIEN-3,17-DIONE -710164.5 down -2517035.8 down 84.0214 541-50-4 C00164 Bifemelane -730554.3 down -2589303.2 down 91.0423 95-55-6 3,4,5-Trimethoxycinnamic acid -771080.75 down -2732941 down 110.0734 16386-93-9 8'-Hydroxydihydroergotamine -202383.47 down -2883357.2 down 306.1352 115956-12-2 C07866 LOBELINE -820229.44 down -2907138.8 down 99.1047 108-91-8 Propafenone glucuronide -546.18994 down -2910034.2 down 144.0418 18294-85-4 C02360 b-D-Glucopyranosiduronic acid, 6-(3-oxobutyl)-2- naphthalenyl -951619.56 down -3090257.5 down 113.0837 61-90-5 C00123 HECOGENIN ACETATE -903851.7 down -3203521 down 144.0571 94-59-7 Epirubicin glucuronide -14177.308 down -3273158.2 down 426.2956 24125-16-4 N-Carbamoyl-DL-aspartic acid -268.7674 down -3370186 down 56.0626 60-29-7 4-Biphenylamine -214595.72 down -3468218.5 down 160.0885 2270-20-4 15(S)-HEDE -980701 down -3475898 down 358.0191 15722-48-2 C07323

7-hydroxy Tetranor Iloprost -1165584.5 down -4131180.8 down 256.1673 73179-89-2 Homoveratric acid -33.28431 down -4283587 down 224.1403 1211-29-6 C11512 N-AcetylCilastatin -12983.593 down -4789502.5 down 103.0997 473-75-6 (5Z,8Z,11Z,14Z)-N-(2-hydroxyethyl) icosa- 5,8,11,14-tetraenamide -3125.8918 down -5524065 down 225.151 1531-12-0 ISOSAFROLE -3898.9019 down -5540756 down 280.1297 58185-92-5 o-Hydroxyaniline -484487.78 down -5907943.5 down 259.1571 525-66-6 C07386 Iopanoic acid -13417.057 down -6461996.5 down 370.0916 43200-80-2 C12808 Mitoxantrone dicarboxylic acid -30906.236 down -6539206.5 down 501.3214 C08804 ETHAVERINE -2034293.9 down -7210146.5 down 101.0841 C01842 Cerebroside C -28.890015 down -7525933.5 down 224.188 454-14-8 C06521 2H-1-Benzopyran-2-one, 3-[1-(4-aminophenyl)-3- oxobutyl]-4-hydroxy-, (S)- (Acenocoumarol metabolite) -343587.47 down -7709318.5 down 349.1908 42595-90-4 4-O-Methyl-gallate -3513683 down -1.25E+07 down 134.0729 103-79-7 Carboxyterbinafine -51.77478 down -1.27E+07 down 543.3313 63163-02-0 5-Hepten-3-ynoic acid, 2,2-dimethyl-7-[(1- naphthalenylmethyl) amino]-, (E)- -41429.324 down -1.50E+07 down 195.0526 50-86-2 5-Hepten-3-ynoic acid, 7-[[(3,4-dihydro-3,4- dihydroxy-1-naphthalenyl) methyl] amino]-2,2- dimethyl- -4940701 down -1.75E+07 down 183.0654 759-65-9 Desmethylondansetron -23614.803 down -2.92E+07 down 251.1148 840-97-1

References

(1) Sahu, A.; Nandakumar, N.; Sawant, S.; Krishna, C. M. The Analyst 2015, 140, 2294-2301. (2) Mehta, K.; Atak, A.; Sahu, A.; Srivastava, S.; C, M. K. The Analyst 2018, 143, 1916-1923. (3) Ferlay, J.; Soerjomataram, I.; Dikshit, R.; Eser, S.; Mathers, C.; Rebelo, M.; Parkin, D. M.; Forman, D.; Bray, F. International journal of cancer 2015, 136, E359-386. (4) Ghanate, A. D.; Kothiwale, S.; Singh, S. P.; Bertrand, D.; Krishna, C. M. Journal of biomedical optics 2011, 16, 025003.