Comparison of the greenness profiles of the reported methods determining favipiravir in biological samples using Analytical Eco-Scale (AES), Green Analytical Procedure Index (GAPI) and Analytical GREEnness (AGREE) metric.

Method	Analytical eco-scale		GAPI	AGREE	Ref.
1	Reagents	PPsa			29
	Polycaprolactone-block-polydimethylsiloxane-block-polycaprolactone polymer	0
	Methyl trimethoxysilane	2
	Acetone	4
	Methylene chloride	2
	Trifluoroacetic acid	4
	Methanol	6
	Acetonitrile	4
	Phosphoric acid	2
	Instruments
	Vortex	0
	Centrifuge	0
	Conditioning device (50 C × h)	2
	Ultrasonic bath	2
	Magnetic stirring	0
	HPLC-UV	1
	Occupational hazard	0
	Waste	0
	Total PPs	29
	Eco-scale	71
2	Reagents	PPs			32
	Acetonitrile	4
	Formic acid	6
	Methanol	6
	Instruments
	Vortex	0
	Centrifuge	0
	LC-MS/MS	2
	Occupational hazard	0
	Waste	3
	Total PPs	21
	Eco-scale	79
3	Reagents	PPs			16
	Acetonitrile	4
	Phosphoric acid	2
	Potassium dihydrogen orthophosphate	0
	Instruments
	Vortex	0
	Centrifuge	0
	UHPLC	0
	Occupational hazard	0
	Waste	3
	Total PPs	9
	Eco-scale	91
4	Reagents	PPs			33
	Acetonitrile	4
	Formic acid	6
	Sodium dihydrogen phosphate	0
	Methanol	6
	Instruments
	Vortex	0
	Centrifuge	0
	Ultrasonic bath	0
	HPLC-DAD	1
	Solvent evaporator	2
	Occupational hazard	3
	Waste	5
	Total PPs	27
	Eco-scale	73
5	Reagents	PPs			23
	Methanol	6
	Acetic acid	4
	Instruments
	Vortex	0
	Centrifuge	0
	Solvent evaporator	2
	LC-MS/MS	2
	Occupational hazard	3
	Waste	3
	Total PPs	20
	Eco-scale	80
6	Reagents	PPs			15
	Tetrahydrofuran	6
	Menthol	1
	Trichloroacetic acid	4
	Acetonitrile	4
	Potassium dihydrogen phosphate	0
	Phosphoric acid	2
	Instruments
	Vortex	0
	Centrifuge	0
	HPLC-UV	1
	Occupational hazard	0
	Waste	3
	Total PPs	21
	Eco-scale	79
7	Reagents	PPs			28
	Acetonitrile	4
	Formic acid	6
	Ammonia	6
	Methanol	6
	Instruments
	Vortex	0
	Centrifuge	0
	HPLC-UV	1
	Occupational hazard	3
	Waste	3
	Total PPs	29
	Eco-scale	71
8	Reagents	PPs			18
	Acetonitrile	4
	Formic acid	6
	NaCl	0
	Anhydrous magnesium sulphate	0
	Methanol	6
	Instruments
	Vortex	0
	Centrifuge	0
	UHPLC-MS/MS	2
	Solvent evaporator	2
	Occupational hazard	3
	Waste	3
	Total PPs	26
	Eco-scale	74
9	Reagents	PPs			27
	Acetonitrile	4
	Phosphoric acid	2
	Methanol	6
	Instruments
	Vortex	0
	Centrifuge	0
	UHPLC-UV	0
	Occupational hazard	0
	Waste	3
	Total PPs	15
	Eco-scale	85
10	Reagents	PPs			13
	Acetonitrile	4
	Phosphoric acid	2
	Gadolinium(iii) chloride hexahydrate	1
	Trihexyl (tetradecyl)phosphonium chloride	4
	Dichloromethane	4
	Perchloric acid	4
	Tetrahydrofuran	6
	Instruments
	Reflux	2
	Vacuum evaporator (drying)	2
	Vortex	0
	Centrifuge	0
	HPLC-UV	1
	Occupational hazard	0
	Waste	3
	Total PPs	33
	Eco-scale	67
11	Reagents	PPs			25
	Acetonitrile	4
	Methanol	6
	Phosphate buffer	0
	Dichloromethane	4
	Instruments
	Solvent evaporator	2
	Vortex	0
	Centrifuge	0
	HPLC-UV	1
	Occupational hazard	3
	Waste	5
	Total PPs	25
	Eco-scale	75
12	Reagents	PPs			21
	Methanol	6
	Acetic acid	4
	Instruments
	Vortex	0
	Centrifuge	0
	LC-MS/MS	2
	Occupational hazard	0
	Waste	3
	Total PPs	15
	Eco-scale	85
13	Reagents	PPs			25
	Methanol	6
	Formic acid	6
	Ammonium format	1
	Acetonitrile	4
	Instruments
	Vortex	0
	Centrifuge	0
	LC-MS/MS	2
	Occupational hazard	0
	Waste	3
	Total PPs	22
	Eco-scale	78
14	Reagents	PPs			20
	Acetonitrile	4
	Formic acid	6
	Methanol	6
	Instruments
	Vortex	0
	Centrifuge	0
	LC-MS/MS	2
	Occupational hazard	0
	Waste	3
	Total PPs	21
	Eco-scale	79
15	Reagents	PPs			14
	Acetonitrile	4
	Phosphoric acid	2
	Perchloric acid	4
	Tetrahydrofuran	6
	Instruments
	Vortex	0
	Centrifuge	0
	HPLC-UV	1
	Occupational hazard	0
	Waste	3
	Total PPs	20
	Eco-scale	80
16	Reagents	PPs			19
	Acetonitrile	4
	Ammonia	6
	Methanol	6
	Instruments
	Vortex	0
	Centrifuge	0
	UHPLC-MS/MS	2
	Occupational hazard	3
	Waste	3
	Total PPs	24
	Eco-scale	76
17	Reagents	PPs			31
	Acetonitrile	4
	Phosphoric acid	2
	HCl	4
	Instruments
	Vortex	0
	Centrifuge	0
	HPLC-UV	1
	Occupational hazard	0
	Waste	3
	Total PPs	14
	Eco-scale	86
18	Reagents	PPs			24
	Methanol	6
	Ethyl acetate	4
	Phosphoric acid	2
	Instruments
	Vortex	0
	Centrifuge	0
	Solvent evaporator	2
	HPLC-UV	1
	Occupational hazard	3
	Waste	3
	Total PPs	21
	Eco-scale	79
19	Reagents	PPs			30
	Brij-35	4
	Methanol	6
	Sodium dodecyl sulfate	4
	Sodium dihydrogen phosphate	0
	Propanol	6
	Instruments
	Vortex	0
	Centrifuge	0
	Solvent evaporator	2
	UPLC-UV	0
	Occupational hazard	3
	Waste	3
	Total PPs	28
	Eco-scale	72

^aPPs for analytical eco-scale were calculated as per ref. 37 as follows: (1) reagent amount PPs: <10 mL (g) = 1; 10–100 mL (g) = 2; >100 mL (g) = 3. (2) Reagent hazard PPs: none = 0; less severe = 1; more severe = 2. Then total PPs = amount PPs × hazard PPs. (3) Energy PPs: ≤ 0.1 kWh per sample = 0, ≤ 1.5 kWh per sample = 1, > 1.5 kWh per sample = 2. (4) Occupational hazard PPs: analytical process hermitization = 0; emission of vapors and gases to air = 3. (5) Waste PPs: none = 0; <1 mL (g) = 1; 1–10 mL (g) = 3; >10 mL (g) = 5.