Table 2 Reported analytical method for the estimation of AT, its metabolites, and co-administered drugs in biological fluids using LC-MS/MS technique

AT and telmisartan

Human plasma

LLE

Isocratic elution; AA (pH 4;10 mM): MeOH (20:80, v/v)

Luna C18 (150 × 4.6 mm, 5 μm)

0.4

MS ESI⁺SIM559

3.8

1–35 ng mL⁻¹r² = 0.9930

----

1.00 ng mL⁻¹

81.48%

[53]

AT, fluvastatin, simvastatin, pravastatin, rosuvastatin, lovastatin, pitavastatin, and metabolites

Human plasma

LLE

Gradient elution; A = water containing 1% ACN, 0.1% FA,2 mM AF, B = ACN containing 1% water, 0.1% FA, 2 mM AF

Hypersil Gold C18 column (100 × 2.1 mm, 1.9 μm)

0.7

HRMS/MSHESI⁺/HESI⁻ SRM559 → 440

4.5

1–100 ng mL⁻¹

----

1.00 ng mL⁻¹

----

[54]

AT

Human plasma

LLE

Gradient elution; A = 0.2 %FA, B = ACN

Acquity UPLC BEH C18 column (100 × 2.1 mm, 1.7 μm)

0.3

MS/MS ESI⁺MRM559.05 → 440

----

0.2–100 ng mL⁻¹r² = 0.9998

----

----

----

[55]

AT, simvastatin, fluvastatin, lovastatin, pitavastatin, rosuvastatin, pravastatin, and metabolites

Human serum

PP-MEPS

Gradient elution; A = ACN, B = AA (0.5 mM)

Acquity UPLC BEH C18 column (50 × 2.1 mm, 1.7 μm)

0.3

MS/MS ESI⁻SRM557.2 → 278.2

2.5

5–1000 ng mL⁻¹r² = 0.999

----

10.00 ng mL⁻¹

----

[56]

0.5

MS/MS ESI⁻SRM557.2 → 278.2

4.4

0.5–500 ng mL⁻¹r² = 0.9984

----

1.00 ng mL⁻¹

----

0.5

MS/MS ESI⁻SRM557.2 → 397

4.4

0.1–100 ng mL^–1r² = 0.9993

----

1.00 ng mL⁻¹

----

AT, o-OH AT, p-OH AT, and AT Lactone

Rat plasma

SPE

Gradient elution; A = ACN, B = 0.1% AcA

ZORBAX Eclipse C18 Analytical column (100 × 4.6 mm, 3.5 μm)

0.4

MS/MS ESI⁺SRM559.47 → 440.03

4.5

0.1–20 ng mL^–1r² = 0.9982

0.05ng mL⁻¹

----

----

[57]

AT, o-OH AT, and p-OH AT

Human plasma

LLE

Isocratic elution; 0.3% FA in water: 0.3% FA in ACN (50:50, v/v)

Purospher STAR RP 18 endcapped column (55 × 2 mm, 3 μm)

0.5

MS/MS ESI⁻557.4 → 278.1

2.4

1.99–80.52 ng mL^–1r² = 0.9954

----

2.04 ng mL⁻¹

82.87%

[58]

AT and amlodipine

Human plasma

LLE

Isocratic elution; ACN:AA buffer (pH 3.0;10 mM) (70:30, v/v)

ZORBAX XDB-C18 column (30 × 2.1 mm, 3.5 μm)

0.15

MS/MS ESI⁺MRM559.3 → 440.2

3.8

0.2–20 ng mL⁻¹r² = 0.9990

0.10ng mL⁻¹

0.20 ng mL⁻¹

94.56%

[59]

AT, o-OH AT, and p-OH AT

Human plasma

LLE

Isocratic elution; ACN:0.20% FA (65:35,v/v)

Luna C18 column, 100 × 4.6 mm, 5 μm)

0.6

MS/MS ESI⁻MRM557.3 → 397.1

3.7

0.2–202 ng mL⁻¹r² ≥ 0.9969

----

----

76.14%

[60]

Simvastatin, lovastatin, AT, and metabolites

Human plasma

PP

Gradient elution; A = Water, B = ACN (0.2% FA and 2 mM AF)

ZORBAX Extend C18 column (50 × 2.1 mm, 3.5 μm)

0.4

MS/MS ESI⁺SRM559.2 → 440.2

8.4

0.1–100 nMr² ≥ 0.9950

----

0.10 nM

102.08%

[61]

AT, o-OH AT, and p-OH AT

Human plasma

SALLE

Gradient elution; A = water (1%FA), B = ACN

Kinetex XB C18 column (50 × 2.1 mm, 2.6 μm)

0.8

MS/MS ESI⁺MRM559.3 → 440.2

2.2

0.02–15 ng mL⁻¹r² = 0.9986

----

0.02 ng mL⁻¹

87.93%

[62]

AT and olmesartan

Human plasma

LLE

Isocratic elution; ACN:MeOH:0.1% FA (80:10:10, v/v/v)

Eclipse Plus C18 column (75 × 4.6 mm, 3.5 μm)

0.5

MS/MS ESI⁺MRM559.1 → 440.2

2.0

2–80 ng mL⁻¹r² = 0.9950

0.19ng mL⁻¹

0.60 ng mL⁻¹

80.26%

[63]

AT and other cardio vascular drug

Human plasma

PP

Gradient elution; A = 0.1% (v/v) aqueous FA with 1.0 mM AF), B = 0.1 % (v/v) FA with 1.0 mM AF in ACN

C18 column (50 × 4.6 mm, 5 μm)

0.6

MS/MS APCI⁺MRM559.6 → 440.3

5.5

----

----

7.20 ng mL⁻¹

90.50%

[64]

AT, metoprolol, amlodipine, pravastatin, rosuvastatin, and metabolites

Human plasma

PP

Gradient elution; A = water with 0.1% FA, B = ACN with 0.1% FA

Acquity UPLC CSH column (50 × 2.1 mm, 1.7 μm)

0.5

MS/MS ESI⁺SRM559 → 440

2.5

0.2–500 ng mL⁻¹r² ≥ 0.9900

0.30 ng mL⁻¹

----

80.00–103.00%

[65]

AT and ezetimibe

Human plasma

LLE

Isocratic elution; 0.2% FA in water:ACN (30:70, v/v)

Eclipse-plus C18 column (100 × 4.6 mm, 3.5 μm)

0.6

MS/MS ESI⁺ MRM559 → 440

2.7

20–3000 ng mL⁻¹r² = 0.9998

----

----

76.32%

[66]

AT, o-OH AT, and p-OH AT

Human plasma

SPE

Isocratic elution; 0.005% FA in water:ACN:MeOH (35:25:40, v/v/v)

Ascentis Express C18 column (75 × 4.6 mm, 2.7 μm)

06

MS/MS ESI⁻ MRM557.4 → 278.1

4.1

0.05–100.138 ng mL⁻¹r² = 0.9991

----

0.05 ng mL⁻¹

77.40%

[67]

Glimepiride, metformin, and AT

Human plasma

PP

Isocratic elution; ACN: AA (pH 3.0;10 mM) (60:40, v/v)

Alltima HP C18 HL column (50 × 4.6 mm, 3 μm)

1.1

MS/MS ESI⁺MRM559.5 → 440.4

1.0

0.5–150.53 ng mL⁻¹r² ≥ 0.9900

----

1.50 ng mL⁻¹

96.72%

[68]

Amlodipine, AT, o-OH AT, and p-OH AT

Human plasma

LLE

Isocratic elution; ACN: AA buffer (20 mM) (50:50, v/v) (0.3% FA mixed)

Cap- cellpak CR 1:4 column (150 × 2 mm, 5 μm).

0.45

MS/MS ESI⁺MRM559.42 → 440.25

5.4

0.035–25 ng mL⁻¹r² = 0.9966

----

0.04 ng mL⁻¹

80.26%

[69]

Amlodipine, AT, o-OH AT, and p-OH AT

Human plasma

PP

Isocratic elution; water:MeOH (14:86, v/v) (pH^a 3.2 with TCA)

Synergi 4 μm polar-RP 80Ǻ column (150 × 4.6 mm, 4 μm)

0.5

MS/MS ESI⁺SRM559.09 → 440.21

5.5

1.5–150 ng mL⁻¹r² = 0.9999

----

1.50 ng mL⁻¹

103.47%

[70]

AT and ezetimibe

Human plasma

LLE

Gradient elution; A = 0.1% FA in water, B = ACN

Acquity UPLC BEH C18 column (50 × 2.1 mm, 1.7 μm)

0.7

MS/MS ESI⁺MRM559.5 → 440.4

1.0

0.1–20 ng mL⁻¹r² = 0.9990

----

0.10 ng mL⁻¹

95.30%

[71]

AT and aspirin

Human plasma

LLE

Isocratic elution; 0.2% AcA buffer:MeOH:ACN (20:16:64, v/v/v)

ZORBAXXDB Phenyl column (75 × 4.6 mm, 3.5 μm)

0.8

MS/MS ESI⁺MRM559.2 → 440

1.3

0.2–151 ng mL⁻¹r² = 0.9900

----

0.60 ng mL⁻¹

82.30%

[72]

AT and glimepiride

Human plasma

LLE

Isocratic elution; 0.1% FA:ACN (30:70, v/v)

ACE 5 C18 column (50 × 4.6 mm, 5 μm)

0.5

MS/MS ESI⁺MRM559.5 → 440.1

1.9

0.2–30 ng mL⁻¹r² ≥ 0.9950

----

0.20 ng mL⁻¹

80.34%

[73]

AT and metabolites

Plasma

SPE, MEPS

Gradient elution; A = ACN, B = AA (pH 4;0.5 mM)

Acquity UPLC BEH C18 column (100 × 2.1 mm, 1.7 μm)

0.25

MS/MS ESI⁺SRM559.5 → 440.4

3.0

0.5–100 nMr² = 0.9993

0.03 Nm

0.08 nM

----

[74]

AT and metabolites

Human plasma

PP

Gradient elution; A = 0.1% v/v glacial AcA in 10% v/v MeOH in water, B = 40% v/v MeOH in ACN

ZORBAX-SB Phenyl column (100 × 2.1 mm, 3.5 μm)

0.35

MS/MS ESI⁺MRM559.2 → 440.2

3.9

0.05–100 ng mL⁻¹r² ≥ 0.9975

----

0.05 ng mL⁻¹

88.60–111.00%

[75]

AT and metabolites

Plasma

PP

Gradient elution; A = water, B = MeOH (Both with 0.10% FA and 2 mM AA)

Raptor Biphenyl column (30 × 3 mm, 5 mm)

0.75–1.2

MS/MS ESI⁺SRM 559.3 → 440.2

----

----

----

----

----

[76]

AT and amlodipine

Human plasma

PP

Gradient elution; A = 0.1% of FA in water, B = 0.1% of FA in ACN

Eclipse XDB-C18 column (100 × 2.1 mm, 3.5 μm)

0.4

MS/MS ESI⁺MRM559.3 → 440.2

----

0.46–1000 ng mL⁻¹r² = 0.9965

----

0.46 ng mL⁻¹

96.23%

[77]

Ramipril, AT, benazepril, and amlodipine

Human plasma

LLE

Isocratic elution; 0.1% FA:ACN (15:85, v/v)

ZORBAX-SB C18 column (50 × 4.6 mm, 5 μm)

1.0

MS/MS ESI⁺MRM559 → 440.2

0.6

0.05–20.5 ng mL⁻¹r² = 0.9900

----

0.26 ng mL⁻¹

67.10%

[78]

AT and metabolites

Human plasma

SPE

Isocratic elution, ACN:0.60% (v/v) AcA (70:30, v/v)

SymmetryC18 column (75 × 4.6 mm, 3.5 μm)

0.5

MS/MS ESI⁺559.2 → 440.2

2.67

0.05–252.92 ng mL⁻¹r² = 0.9900

----

0.05 ng mL⁻¹

66.18%

[79]

AT and metabolites

Human plasma

SPE

Isocratic elution; ACN:MeOH:0.1% FA in water (50:30:20, v/v/v)

Cyno analytical column (125 × 4 mm, 5 μm)

0.5

MS/MS ESI⁻MRM557.31 → 397.16

2.4

0.2–40 ng mL⁻¹r² ≥ 0.9900

0.06ng mL⁻¹

----

50.00–68.00%

[80]

Simvastatin and AT

Human serum

SPE

Gradient elution; A = ACN, B = AA(pH 4.0; 0.5 mM)

Acquity UPLC BEH C18 column (100 × 2.1 mm, 1.7 μm)

0.25

MS/MS ESI⁺,SRM559 → 440

2.51

0.1–100 nMr² = 0.9999

0.05 nM

0.15 nM

85.66%

[81]

AT and o-OH AT

Human plasma

LLE

Isocratic elution; ACN:water (95:5, v/v)(0.2 % FA mixed)

Sunfire C18 column (100 × 2.1 mm, 3.5 μm)

0.5

MS/MS ESI⁺MRM559.4 → 440.5

2.66

0.1–10 ng mL⁻¹r² = 0.9970

----

0.10 ng mL⁻¹

85.73%

[82]

AT and p-OH AT

Human plasma

SPE

Isocratic elution; 0.1% AcA in water: ACN (40:60, v/v)

Genesis C18 column (50 × 2.1 mm, 4 μm)

0.2

MS/MS ESI⁺MRM559.3 → 440.1

1.70

0.229–91.6 ng mL⁻¹r² = 0.9960

----

0.23 ng mL⁻¹

53.06%

[83]

AT

Human plasma

LLE

Isocratic elution; AA (5 mM): MeOH: Methanoic acid (30:70:0.1, v/v/v)

Hypersil C18 column (150 × 4.6 mm, 5 μm)

1.0

MS ESI⁺SIM559.25

4.45

0.25–20 ng mL⁻¹r² = 0.9996

----

0.25 ng mL⁻¹

58.13%

[84]

AT and o-OH AT

Human plasma

LLE

Isocratic elution, ACN:0.1% AcA (70:30, v/v)

Atlantis d-C18 column (10 × 3 mm, 3 μm)

0.3

MS/MS ESI⁺MRM mode559 → 440

3.1

0.10–40 ng mL⁻¹r² = 0.9990

0.02 ng mL⁻¹

0.10 ng mL⁻¹

91.50%

[85]

AT and metabolites

Human plasma

LLE

Iscocartic elution; 0.03% FA:ACN (30:70, v/v)

Symmetry C18 column (100 × 4.6 mm, 5 μm)

1.0

MS/MS ESI⁺ MRM559 → 440

1.8

0.1–20 ng mL⁻¹

----

0.10 ng mL⁻¹

54.20%

[86]

Rosuvastatin, simvastatin, AT, and metabolites

Human plasma

LLE

Gradient elution; A = 10 mM AF and 0.04% FA, B = ACN.

Acquity UPLC BEH C18 column (100 × 2.1 mm, 1.7 μm)

0.4

MS/MS ESI⁺559.2 → 440.3

3.2

0.25–100 ng mL⁻¹r² = 0.9910

----

0.25 ng mL⁻¹

97.20%

[87]

AT and metabolites

Human plasma

SPE

Gradient elution; A = ACN:FA (1 mM) (30:70, v/v), B = ACN: FA (1 mM) (60:40, v/v)

Omnisphere C18 column (30 × 2 mm, 3 μm)

0. 2

MS/MS ESI⁺ SRM559.0 → 440.2

6.2

0.2–30 ng mL⁻¹r² = 0.9910

0.06 ng mL⁻¹

----

53.00–78.00%

[88]

AT and metabolites

Human serum

LLE

Gradient elution; A = 950 mL of water +50 mL of MeOH+ 43 mL of 88% FA, B = 950 mL of ACN + 50 mL of MeOH+43 mL of 88% FA.

YMC Basic column (50 × 2 mm, 5 mm)

0.3

MS/MS ESI⁺SRM 559.2 → 440.2

2.78

0.5–200 ng mL⁻¹

----

0.50 ng mL⁻¹

60.00–100.00%

[89]

AT and metabolites

Human plasma

LLE

Isocratic elution; ACN:0.1% AcA (70:30, v/v)

YMC J’Sphere H80 C18 column (150 × 3.2 mm, 4 mm)

0.2

MS/MS ESI⁺MRM559.3 → 440.2

4.3

0.250–25 g mL⁻¹r² = 0.9989

----

0.25 ng mL⁻¹

98.40%

[90]

Dog plasma

4.8

0.250–25 ng mL⁻¹r² = 0.9994

98.90%

Rat plasma

3.5

0.250–25 ng mL^–1r² = 0.9995

98.00%

AT and metabolites

Human plasma

PP

Isocratic elution; 0.2% FA:ACN (55:45, v/v)

Acquity UPLC BEH C18 column (50 × 2.1 mm, 1.7 μm)

0.4

MS/MS ESI⁺SRM 559.2 → 440.2

2.4

0.025–200 ng mL⁻¹r² = 0.988

----

0.02 ng mL⁻¹

97.37%

[91]

AT, mevastatin, pravastatin, rosuvastatin, pitavastatin, fluvastatin, simvastatin, and lovastatin

Human urine

Shoot and dilute method

Gradient elution; A= 0.1% AcA, B = ACN

Kinetex C18 column (50 × 3 mm, 2.6 μm)

0.35

MS/MS ESI⁺MRM559.3 → 250.2

6.4

1–500 ng mL⁻¹r² = 0.9946

----

----

92%

[92]

Bisoprolol, clopidogrel, and AT

Human plasma

PP

Gradient elution; A = water, B = ACN (0.1% FA)

Halo C18 column (50 × 2.1 mm, 2.7 μm)

0.5

MS/MS ESI⁺ MRM559.3 → 440.3

3.5

0.5–125 ng mL⁻¹r² = 0.9950

----

0.50 ng mL⁻¹

102.40%

[93]

AT

Human plasma

PP

Gradient elution; A = 0.2% (v/v) FA in water, B = ACN

Leapsil C18 column (100 × 2.1 mm, 2.7 μm)

0.3

MS/MS ESI⁻MRM557.0 → 453.0

2.0

0.01–200 ng mL⁻¹r² = 0.9992

----

0.05 ng mL⁻¹

85.63–92.51%

[94]

AT and amlodipine

Human plasma

LLE

Isocratic elution; ACN: AF (pH 4.5;10 mM) (70:30, v/v)

Acquity UPLC BEH C18 column (50 × 2.1 mm, 1.7 μm)

0.25

MS/MS ESI⁺MRM557 → 440.2

0.66

0.05–50 ng mL⁻¹r² = 0.9996

----

0.05 ng mL⁻¹

91.30–94.00%

[95]

AT and metabolites

Human plasma

SPE

Gradient elution; A = 0.1% AcA in water, B = ACN

Genesis C18 column (50 × 2.1 mm, 4 μm)

----

MS/MS ESI⁺ MRM559.4 → 440.3

----

r² ≥ 0.9900

----

----

94.31%

[96]

AT

Human Plasma

μ-SPE

Gradient elution; A = AA (10 Mm), B = ACN

C18 column (100 × 3 mm, 5 μm)

0.6

MS/MS ESI⁺ MRM559.2 → 440.1

4.5

0.2–80 ng mL⁻¹r² = 0.9965

0.05 ng mL⁻¹

0.20 ng mL⁻¹

94.60%

[97]

AT and niacin

Human plasma

LLE

Isocratic elution; ACN: 0.1% FA (80:20, v/v)

Hypurity Advance column (50 × 4.6 mm, 5 mm)

0.8

MS/MS ESI⁺MRM559.0 → 440.3

1.1

0.1–30 ng mL⁻¹r² ≥ 0.9900

----

----

77.83%

[98]

AT and olmesartan

Rat plasma

PP

Isocratic elution; ACN: 0.04% glacial AcA (80:20, v/v)

Aquasil C18column (50 × 2.1 mm, 5 μm)

0.25

MS/MS ESI⁺MRM559.0 → 440.0

1.68

1–1000ng mL⁻¹r² = 0.9998

0.15 ng mL⁻¹

1.00 ng mL⁻¹

85.72%

[99]

AT and metabolites

Human plasma

LLE

Isocratic elution; ACN: Water(75:25, v/v) (0.05 % v/v FA mixed)

Acquity UPLC HSS T3 column (100 × 3 mm, 1.8 μm)

0.3

MS/MS ESI⁺MRM559.4 → 440.1

2.30

0.2–40 ng mL⁻¹

----

0.20 ng mL⁻¹

48.53%

[100]