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Table 3 Bioanalytical/metabolite studies

From: Ultra-high performance liquid chromatography-MS/MS (UHPLC-MS/MS) in practice: analysis of drugs and pharmaceutical formulations

UPLC (drug)

Column

Mobile phase system

Detector

Extraction method

Biological or/metabolite studies or pharmaceutical

Mode of analysis

Ref

Antibiotics agents

Amoxicillin, Ampicillin, cefuroxime, cefazolin, ceftazidime, meropenem, piperacillin, clavulanic acid, and tazobactam

BEH C18

Water (A) Acetonitrile (B) both containing 0.1% formic acid

5% solution (B) at 0.5 min to 55% at 4.0 min and column was rinsed with 95% solution (B) for 0.5 min and re-equilibrated to starting conditions for 1 min

Triple-quadrupole

PP

Biological

Gradient

[33]

Cefuroxime lysine

BEH C18

Acetonitrile: 0.1% formic acid in 10 mM Ammonium Acetate (40:60, v/v).

Quadrupole

LLE

Biological

Isocratic

[34]

Clarithromycin

BEH C18

(A) 50 mM ammonium Acetate solution and (B) Acetonitrile. 0.0 min 50 (A):50(B), 1.5 min 10(A): 90(B), 1.7 min 10(A): 90(B), 1.8 min 50(A):50(B), 2.0 min 50(A):50(B)

Triple-quadrupole mass spectrometer

LLE

Biological

Gradient

[35]

Indolinone derivative

HSS T3 column

Water (A) and (B) acetonitrile, both containing 0.1% formic acid 0–0.5 min, (B) 2%;0.5–2 min, (B) 2–100%; 2–2.5 min, (B) 100%; 2.5–2.6 min, (B) 100–2%; 2.6–4 min, (B) 2%

Mass detector

PP

Biological

Gradient

[36]

Ertapenem

Agilent Zorbax Eclipse Plus C18

Water : Acetonitrile (95:5% v/v) both containing 0.1 % formic Acid

Triple-quadrupole

LLE

Biological

Gradient

[37]

Amikacin, flucloxacillin, meropenem, penicillin G and vancomycin

RP18 column

Water (A) and methanol (B), both containing 4% of formic acid

0–0.3 min, 20% (B); 0.3–1.0 min, 50% (B); 1.0–2.0 min

50% (B); 2.0–2.7 min, 75% (B), 2.7–5.3 min, 75% (B)

5.3–5.5 min, 20% (B)

Triple-quadrupole mass spectrometer

PP

Biological

Gradient

[38]

Cephalomannine

BEH C18

0.1% formic acid in water (A) and acetonitrile (B)

0–0.6 min, 20–85% (B); 0.6–1.8 min, 85% (B); 1.8–2.0 min, 80–30% (B)

Triple-quadrupole mass spectrometer

PP

Biological

Gradient

[39]

Tedizolid and linezolid

BEH C18

(A) 0.1% formic acid in water and (B) Acetonitrile

0–0.3 min, 20–95% (B); 0.3–1.5 min, 95–95% (B); 1.5–1.6 min, 95–20% (B); 1.6–3.0 min, 20–20% (B)

Mass spectrometer

PP

Biological

Gradient

[40]

Anticancer agents

Amrubicin

BEH C18

(A) Acetonitrile: water, (1:99% v/v), 5 mM formic acid and (B) acetonitrile: water, (99:1% v/v), also containing 5 mM formic acid 0.00 min, 100(A) :0(B); 0.30 min, 0(A):100 (B); 0.70 min, 0(A):100 (B); 1.50 min, 100(A): 0(B)

Triple-quadrupole

SPE

Metabolite

Gradient

[41]

Solasonine

HSS T3 column

(A) 0.1% formic acid and (B) acetonitrile. 0–0.5 min, 15% (B); 0.5–3.5 min, 15–75% (B); 3.5–4.0 min, 75–85% (B); 4.0–5.0 min, 85% (B)

Triple-quadrupole mass spectrometer

PP

Biological

Gradient

[42]

Berberrubine

BEH C18

(A) 0.1% formic acid and (B) acetonitrile. 1.5 min, 30–60% (B); within 0.5 min, 95% (B); then decreased to 30% (B) within in 0.1 min, then maintained 30% for 0.4 min

Triple-quadrupole mass spectrometer

LLE

Biological

Gradient

[43]

Pomalidomide

BEH C18

Acetonitrile: 10 mM Ammonium Acetate (80:20% v/v)

Triple-quadrupole mass spectrometer

LLE

Biological

Isocratic

[44]

Docetaxel

BEH C18

(A) Water containing 0.5% formic acid (pH 2.23) and (B) 0.5% formic acid in acetonitrile (pH 2.24). 0–0.9 min, 90% (A); 0.9–1.6 min, 100% (B); 1.6–1.7 min, 90% (A), 1.7–2.5 min, 90% (A)

Quadrupole

LLE

Biological

Gradient

[45]

Indolinone derivative

HSS T3 column

Water (A) and (B) acetonitrile, both containing 0.1% formic acid. 0–0.5 min, 2% (B); 0.5–2 min, 2–100% (B); 2–2.5 min, 100% (B); 2.5–2.6 min, 100–2% (B); 2.6–4 min, 2% (B)

Mass detector

PP

Biological

Gradient

[36]

Lenalidomide

BEH C18

Acetonitrile: water: formic acid (65:35:0.1% v/v/v)

Triple-quadrupole mass spectrometer

PP

Biological

Isocratic

[46]

Paclitaxel

BEH C18

Methanol–0.1% aqueous formic acid

(75: 25% v/v)

Triple-quadrupole mass spectrometer

LLE

Biological

Isocratic

[47]

Irinotecan and 7-ethyl-10 hydroxycamptothecin (SN-38)

BEH C18

(A) Ammonium acetate Buffer (10 mM; pH 3.5) with 0.1% formic acid and (B) acetonitrile. 0 min, 20% (B); 3 min, 20–70% (B), 0.2 min, 70–98% (B), 0.7 min 98% (B); 0.2 min, 98–20% (B)

Quadrupole

SPE

Biological

Gradient

[48]

Anticancer c-Met

inhibitor LS-177

C18 column

(A) Acetonitrile and (B) 0.1% formic acid in water. 0 min, 20% (A); 1 min, 80% (A); 2 min, 80% (A); 2.5 min, 20% (A); 3 min, 20% (A)

Triple-quadrupole mass spectrometer

LLE

Biological

Gradient

[49]

TM-2

C18 column

(A) Acetonitrile and (B) 2 mmol/L ammonium acetate in water. 1.5 min, 60–90% (A); 2.8 min, 90% (A); 3.5 min, 90–60% (A)

Triple-quadrupole mass spectrometer

LLE

Biological

Gradient

[50]

Methotrexate polyglutamates

BEH C18

(A) 10 mM Ammonium bicarbonate buffer With 5 mM of the desired ion-pair adjusted to pH 7.5 with formic acid and (B) acetonitrile. 1 min, 90% (A); 9 min, 70% (A): 30% (B)

Triple-quadrupole mass spectrometer

PP

Biological

Gradient

[51]

Ciprofloxacin, cyclophosphamid, tamoxifen, and azathioprine

HSS T3

(A) 0.1 % formic acid (A) and (B) acetonitrile. 0 min, 90% (A) and 5% (B); 10 min, 0% (A) and 100 % (B)

Triple-quadrupole mass spectrometer

SPE

Pharmaceutical

Gradient

[52]

Temozolomide

BEH C18

(A) Water (containing 0.1% formic acid and 10 mM ammonium acetate) and (B) acetonitrile. 0 min, 20% (B); 2 min, 20–50% (B); 1 min, 50% (B); 1 min, 50–20% (B)

Quadrupole mass spectrometer

PP

Biological

Gradient

[53]

Dendrobine

BEH C18

(A) 0.1% formic acid and (B) acetonitrile. 0–1.0 min, 20–40 (B); 2 min, 40–95% (B), 0.5 min, 95% (B); then decreased to 20% (B) within 0.1 min, maintained at 20% (B) for 0.4 min

Triple-quadrupole mass spectrometer

PP

Biological

Gradient

[54]

Simotinib

Zorbax SB-C8 column

0.1 % formic Acid with 10 mM ammonium formate: methanol (20:80% v/v)

Mass detector

LLE

Biological

Isocratic

[55]

Nintedanib

BEH C18

(A) acetonitrile and (B) 0.1% formic acid in water

0–0.3 min, 20–95% (A); 0.3–2.0 min, 95–95% (A); 2.0–2.1 min, 95–20% (A); 2.1–3.0 min, 20–20% (A)

Triple-quadrupole mass spectrometer

PP

Metabolite

Gradient

[56]

Letrozole

C18 column

(A) Acetonitrile and 0.1% formic acid in water (B). 0 min, 20% (A): 80% (B); 0.3 min, 20% (A): 80% (B); 2 min, 95% (A): 5% (B); 2.5 min, 95% (A): 5% (B); 2.6 min, 20 % (A): 80% (B)

Triple-quadrupole mass spectrometer

PP

Biological

Gradient

[57]

Parthenolide

BEH C18

(A) Acetonitrile and 0.1% formic acid in water (B). 0–0.3 min, 20–95% (B); 0.3–1.5 min, 95–95% (B), 1.5–1.6 min, 95–20% (B)

Triple-quadrupole mass spectrometer

SPE

Biological

Gradient

[58]

Tamoxifen

BEH C18

(A) 10 mM Ammonium formate in water and acetonitrile (B) both are containing 0.1%formic acid

0.0 min, 70%(A): 30%(B); 9.0 min, 48% (A): 52%(B); 9.01 min, 48% (A): 52%(B); 9.50 min, 70% (A): 30%(B); 13 min 70% (A): 30%(B)

Triple-quadrupole mass spectrometer

PP

Metabolite

Gradient

[59]

Vincristine

HSS T3 column

(A) Methanol and (B) water containing 0.2% formic acid. 3 min, 30–95% (A); and returned to initial condition within 1 min

Triple-quadrupole mass spectrometer

LLE

Biological

Gradient

[60]

Palonosetron

HSS T3 column

Methanol : water containing 0.1% formic acid 80: 20% v/v

Triple-quadrupole

LLE

Biological

Isocratic

[61]

Kurarinone

BEH C18

(A) Acetonitrile and 0.1% formic acid in water (B)

0–0.3 min, 30–30% (A); 0.3–1.0 min, 30–90% (A); 1.0–2.0 min, 90–90% (A); 2.0–2.1 min, 90–30% (A); 2.1–3.0 min, 30–30% (A)

Triple-quadrupole

LLE

Biological

Gradient

[62]

Antiviral agents

Elbasvir

BEH C18

(A) Acetonitrile and water (containing 5.0 mM ammonium acetate with 0.01% acetic acid, pH 4.5) (B)

0.0–0.5 min, 90–90% (A)

0.5–1.2 min, 90–5% (A); 1.2–2.0 min, 5–5% (A); 2.0–2.2 min, 5–90% (A); 2.2–3.0 min, 90–90% (A)

Triple-quadrupole

PP

Biological

Gradient

[63]

Daclatasvir

HSS C18

10 mM Ammonium formate, pH 3.5 and acetonitrile (50:50% v/v)

Quadrupole

LLE

Biological

Isocratic

[64]

Ribavirin, sofosbuvir

BEH C18

(A) Acetonitrile and 0.1% formic acid in water (B)

0–0.5 min, 10–10% (A); 0.5–1.0 min, 10–95% (A); 1.0–2.0 min, 95–95% (A); 2.0–2.1 min, 95–10% (A); 2.1–3.0 min, 10–10% (A)

Triple-quadrupole mass spectrometer

PP

Metabolite

Gradient

[65]

Atazanavir, Darunavir and Ritonavir

C18 column

(A) 10 mM Ammonium Formate, pH 4.0, adjusted with formic acid in water, and acetonitrile (B). 0.0–0.8 min, 50%(A) and 50%(B); 0.8–1.2 min, 30%(A) and 70%(B)

Mass detector

PP

Biological

Gradient

[66]

Oleanolic acid

C18 column

10 mM Ammonium Acetate with 0.1% formic acid in water: acetonitrile (10: 90% v/v)

Triple-quadrupole mass spectrometer

SPE

Biological

Isocratic

[67]

Antifungal agent

Tizoxanide

BEH C18

Aq. ammonium formate buffer 10 mM, adjusted to pH 3.0 with formic acid, and acetonitrile (40: 60% v/v)

Mass detector

LLE

Biological

Isocratic

[68]

Voriconazole

BEH C18

Acetonitrile and water containing 1% formic acid (45: 55% v/v)

Triple-quadrupole mass spectrometer

LLE

Biological

Isocratic

[69]

Amphotericin B

BEH Shield RP18 column

(A) Methanol: acetonitrile (50 : 50% v/v) containing 0.1% formic acid; and (B) 10 mM ammonium formate (pH 3 ± 0.2), containing 0.2% formic acid and 1% acetonitrile

0.0–2.0 min, 35–90% (A); 2.0–2.7 min, 90–35% (A)

Triple-quadrupole mass spectrometer

SPE

Biological

Gradient

[70]

Fluconazole, Itraconazole, Hydroxyitraconazole, Posaconazole, Voriconazole

C18 column

(A) 10 mM Ammonium formate in ultrapure water with 0.1% formic acid and acetonitrile with 0.1% formic acid (B)

Triple-quadrupole mass spectrometer

PP

Biological

Isocratic

[71]

Posaconazole

BEH C18

(A) 10 mM Ammonium formate in water containing 0.1% formic acid, (B) 1% acetic acid in methanol, and (C) 1% acetic Acid in acetonitrile. 0–0.9 min, 90% (A) and 10% (B); 0.9–1.9 min, 5% (A) and 95% (B); 1.9–2 min, 100% (B); 2–3.6 min. 100% (C); 3.6–3.7 min, 90% (A) and 10% (B); 3.7–5.0 min, 90% (A) and 10% (B)

Triple-quadrupole mass spectrometer

PP

Biological

Gradient

[72]

Cardiovascular agents

Atorvastatin, Ezetimibe

BEH C18

(A) 0.1% Formic acid in water : (B) acetonitrile (95: 5% v/v)

0.0–0.4 min, 95% (A) and 5%(B); 0.4–1.1 min 10 %(A) and 90% (B); 1.1 min, 95% (A) and 5% (B)

Triple-quadrupole

LLE

Biological

Gradient

[73]

4-hydroxyphenyl carvedilol

BEH C18

Acetonitrile- 4.0 mM ammonium formate, pH 3.0 adjusted with 0.1% formic acid (78: 22% v/v)

Triple-quadrupole mass spectrometer

SPE

Metabolite

Isocratic

[74]

Ivabradine, Reboxetine, Metoprolol

BEH C18

(A) Water and (B) methanol, both containing 2 mM ammonium acetate.0.0–0.5 min, 20% (B); 0.5–3.0 min, 20–90% (B); 3.0–3.5 min, 90% (B) 3.5–4.5 min, 20% (B)

Quadrupole mass spectrometer

LLE

Biological

Gradient

[75]

Meldonium

BEH HILIC column

Water: acetonitrile: formic acid (adjusted to pH 3.0 with 12.5% ammonia hydroxide) (25: 70: 5% v/v/v)

Triple-quadrupole mass spectrometer

PP

Biological

Isocratic

[76]

Candesartan, Hydrochlorthiazide

C18 Phenomenex

Methanol : Acetonitrile 1 (15: 85% v/v)

Triple-quadrupole mass spectrometer

LLE

Biological

Isocratic

[77]

Doxazosine

BEH C18

(A) and (B) consisted of 0.05 (w/v) pentadecafluorooctanoic acid in acetonitrile and 0.05 (w/v) pentadecafluorooctanoic acid in water. 1.0–1.45 min, 10–99% (A); 1.45–1.55 min, 99–10% (A); 1.55–2.0 min, 10% (A)

Triple-quadrupole mass spectrometer

LLE

Biological

Gradient

[78]

Lercanidipine

BEH C18

70% Acetonitrile in water containing 0.2% v/v formic acid

Triple-quadrupole mass spectrometer

LLE

Biological

Isocratic

[79]

Aliskiren Hemifumarate, Amlodipine Besylate and Hydrochlorothiazide

BEH C18

0.1% Formic acid in ammonium acetate buffer (0.02 M, pH 3.5) and Methanol

(25: 75% v/v)

Triple-quadrupole mass spectrometer

LLE

Biological

Isocratic

[80]

Irbesartan

BEH C18

Acetonitrile: Methanol: 10 mM Ammonium acetate (70:15: 15% v/v/v)

Triple-quadrupole

SPE

Biological

Isocratic

[81]

Amlodipine, benazeprile and benazeprilat

BEH C18

(A) 0.1% Formic acid and Acetonitrile (B)

0–0.2 min, 95% (A) and 5% (B); 0.2–0.3 min, 0%(A) and 100%(B); 0.3–2.0 min, 0%(A) and 100%(B); 2.0–2.5 min, 95% (A) and 5% (B), 2.5 min, 95% (A) and 5% (B)

Triple-quadrupole mass spectrometer

LLE

Biological

Gradient

[82]

Candesartan

Betasil C8 column

Methanol : ammonium tri-floro acetate buffer with formic acid (60: 40% v/v)

Mass detector

PP

Biological

Isocratic

[83]

N-butylscopolamine

C18 column

Acetonitrile: 5 mM ammonium acetate: 0.1% formic acid (90: 10% v/v)

Triple-quadrupole mass spectrometer

SPE

Biological

Isocratic

[84]

Udenafil

BEH C18

Acetonitrile: 0.1% formic acid

(75: 25% v/v)

Quadrupole mass spectrometer

LLE

Metabolite

Isocratic

[85]

Alprostadil

BEH C18

(A) Acetonitrile and water (B), containing 0.1% formic acid

0.0–0.6 min, 30% (A); 0.6–0.8 min, 60% (A); 1.4 min, 30% (A)

Quadrupole mass Spectrometer

LLE

Biological

Gradient

[86]

Analgesic agents

Sumatriptan

Hypersil gold C18

Methanol:water (90:10% v/v)

Mass detector

PP

Biological

Isocratic

[87]

Sufentanil

BEH C18

Acetonitrile : water (4:55% v/v)

Triple-quadrupole mass spectrometer

SPE

Biological

Isocratic

[88]

Mitragynine

BEH HILIC column

10 mM Ammonium formate buffer containing 0.1% formic acid: acetonitrile (15:85% v/v)

Quadrupole

LLE

Biological

Isocratic

[89]

Tapentadol and tapentadol-O-glucuronide

BEH C18

0.01 M Ammonium formate (adjusted to pH 4 using formic acid) (A) and methanol (B). For Tapentadol-0.00 min, 80% (A):20%(B); 0.85 min, 65%(A):35%(B); 0.90 min, 2%(A):98% (B); 1.25 min, 2%(A):98% (B); 1.30 min, 80% (A): 20%(B); 1.60 min, 80% (A): 20%(B)

Tapentadol-O-glucuronide-0.0 min, 80% (A): 20%(B); 0.50 min, 70% (A): 30%(B); 0.55 min, 2% (A): 98%(B); 1.05 min, 2% (A): 98%(B); 1.10 min, 80% (A): 20%(B); 1.50 min, 80% (A): 20%(B)

Triple-quadrupole mass spectrometer

SPE

Biological

Gradient

[90]

Dexmedetomidine

BEH C18

0.1% Formic acid in water (A) and 0.1% formic acid in acetonitrile (B). 0 min, 25%(B); 3.0 min, 25%(B); 3.1 min, 95%(B); 5.0 min, 95%(B); 8.0 min, 2%(B)

Triple-quadrupole mass spectrometer

SPE

Biological

Gradient

[91]

Nalbuphine

BEH HILIC column

Acetonitrile : water (83:17% v/v) that contained 0.2% formic acid and 4 mM ammonium formate

Triple quadrupole mass spectrometer

LLE

Biological

Isocratic

[92]

Buprenorphine and norbuprenorphine

BEH C18

Ammonium formate buffer 20 mM adjusted to pH 3.05 with formic acid (A) and acetonitrile (B) (90:10% v/v)

0.0 min, 10 % (B); 2.5 min, 25% (B); 3.2 min, 25% (B); 5.0 min. 30% (B)

Quadrupole mass spectrometer

PP

Biological

Gradient

[93]

Anti-steroid

Testosterone and 5-dihydrotestosterone

BEH C18

(A) Water, (B) consisted of 2 mM ammonium acetate (native pH) in acetonitrile: water (98:2% v/v)

0.1 min, 0% (B); 1.0 min, 30% (B); 2.0 min, 32% (B); 3.4 min, 32% (B)

Triple-quadrupole

LLE

Biological

Gradient

[94]

Triamcinolone acetonide palmitate and triamcinolone acetonide

Phenomenex Luna C18 column

(A) Acetonitrile and (B) 0.1% ammonia solution. 0–1.3 min, 34% (A); 1.3–1.5 min, 34–95%(A); 1.5–5.0 min, 95% (A); 5.0–5.2 min, 95–34% (A); 5.2–5.5 min, 34% (A)

Triple-quadrupole mass spectrometer

LLE

Biological

Gradient

[95]

Anti-inflammatory (NSAID)

Hesperetin

Chiralpak IA-3

(A) Water with 0.1% CHOOH and (B) acetonitrile with 0.1% CHOOH. 0 min, 33% (B); 0.5 min 33% (B); 5 min 40% (B); 5.1 min, 100% (B); 6 min, 100% (B); 6.1 min 33% (B); 8 min 33% (B)

Triple-quadrupole

SPE

Biological

Gradient

[96]

Epiafzelechin a flavan-3-ol with osteoprotective

BEH C18

Water (A) and acetonitrile (B) both containing (0.1% Formic Acid v/v) 1–11 min, 0–70% (B); 0–1 min, 100 % (A); 11–16 min, 100% (A)

Triple-quadrupole mass spectrometer

LLE

Biological

Gradient

[97]

E6005, Phosphodiesterase 4 inhibitor

BEH C18

(A) Water: acetonitrile: 1 mol/L ammonium formate (950:50: 5% v/v/v) and (B) water: acetonitrile: 1 mol/L ammonium formate (100:900: 5% v/v/v). Gradient-2.0 min, 5–95% (B); Isocratic- 2.0 min, 95% (B); 1.5 min, 5% (B)

Triple-quadrupole mass spectrometer

SPE

Metabolite

Gradient/Isocratic

[98]

Naringin

BEH C18

Acetonitrile-0.4% acetic acid (80: 20% v/v)

Triple-quadrupole mass spectrometer

LLE

Biological

Isocratic

[99]

Ibuprofen

BEH C18

Water: methanol (35:65% v/v) both containing 10 mM ammonium acetate and 0.1% formic acid. 0–12 min, 35% (A) and 65% (B); 12.01–14 min 100% (B); 15.1 min, 35% (A) and 65% (B)

Triple-quadrupole mass spectrometer

LLE

Biological

Gradient

[100]

Avicularin

BEH C18

0.1% Formic acid in water (A) and (B) acetonitrile. 0–0.50 min, 30–80% (B); 0.50–1.40 min, 80 % (B); 1.40–1.60 min, 80–30% (B)

Triple-quadrupole mass spectrometer

PP

Biological

Gradient

[101]

Hupehenine

BEH C18

0.1% Formic acid (A) and Acetonitrile (B) 0.0–2.0 min, 40–90 % (B); maintained for 0.5 min, 90%(B); 90–40% (B) within 0.1 min and then maintained 0.4 min, for 40% (B)

Triple-quadrupole mass spectrometer

LLE

Biological

Gradient

[102]

Picfeltarraenins IA and IB

C18 column

Methanol:water (70 : 30% v/v)

Mass detector

PP

Biological

Isocratic

[103]

Diclofenac sodium

BEH C18

Acetonitrile–0.1% ammonium hydroxide aqueous solution (20:80% v/v). 0.0 min, 20% (A); 0.6–1.5 min, 50% (A); 1.6–2.0 min, 20% (A)

Triple-quadrupole mass spectrometer

LLE

Biological

Gradient

[104]

21-hydroxy deflazacort

BEH C18

Acetonitrile and 4.0 mM ammonium formate, pH 3.5 (90:10% v/v)

Triple-quadrupole mass spectrometer

SPE

Biological

Isocratic

[105]

Acetaminophen and dihydrocodeine

BEH C18

(A) 0.1% formic acid in water and (B) Acetonitrile

0–0.3 min, 50–95% (B); 0.3–0.9 min, 95–95% (B); 0.9–1.0 min, 95–50% (B)

Triple-quadrupole mass spectrometer

PP

Biological

Gradient

[106]

Anti-diabetes

Glipizide

BEH C18

(A) Acetonitrile and water containing 1% formic acid (B). 0.0 min, 30 % (A):70%(B); 0.3 min, 75% (A)25% (B); 0.7 min, 75% (A) 25% (B); 1.0 min, 30% (A): 70% (B)

Triple-quadrupole mass spectrometer

SPE

Biological

Gradient

[107]

Lysophosphatidylcholine

BEH C18

(A) 0.1% Formic acid in water, (B) 0.1% formic acid in acetonitrile. 0 min, 100% (A); 37 min, 100% (B)

Mass detector

PP

Metabolite

Gradient

[108]

Miglitol

C18 inertsil column

Acetonitrile and 2 mM Ammonium Acetate (pH 3.5, 80: 20% v/v)

Triple-quadrupole mass spectrometer

LLE

Biological

Isocratic

[109]

Exenatide

C18 column

0.2% Formic acid (A) and methanol (B)

1.5 min, 10% (B); 1.0 min, 10–90% (B); 0.5 min, 90% (B) a linear decrease from 90–10% (B) in 0.1 min

Mass detector

SPE

Biological

Gradient

[110]

Anti-depressant

Vortioxetine

BEH C18

0.1% Formic acid in water (A) and acetonitrile (B). 0–0.5 min, 20–95% (A); 0.5–1.9 min, 95–95% (A); 1.9–2.0 min, 95–20% (A); 2.0–3.0 min, 20–20% (A)

Triple-quadrupole mass spectrometer

PP

Biological

Gradient

[111]

Bupropion

BEH Phenyl column

(A) Ammonium formate buffer (2 mM, pH 4.0) and (B) acetonitrile. 3.5 min, 95% (A); 4.2 min, 70% (A); 4.7 min, 68.5% (A); 4.8 min, 5% (A)

5.7 min, 95% (A)

Triple-quadrupole mass spectrometer

SPE

Metabolite

Gradient

[112]

Venlafaxine and O-desmethylvenlafaxine

BEH C18

10 mmol/L Ammonium acetate and methanol (85: 15% v/v)

Triple-quadrupole

SPE

Biological

Isocratic

[113]

Paroxetine

Hypersil Gold C18 column

Acetonitrile and 0.1% Glacial acetic acid

(50: 50% v/v)

Triple-quadrupole mass spectrometer

LLE

Biological

Isocratic

[114]

Antiepileptic agents

Carbamazepine, carbamazepine-10,11-epoxide, gabapentin, lamotrigine, levetiracetam

BEH Phenyl column

5 mM Ammonium bicarbonate buffer pH 7.9 (A) and methanol (B)

0.00 min, 97.5% (A): 2.5%(B); 1.00 min, 95.0% (A): 5.0% (B); 2.00 min, 0.0% (A): 30.0% (B); 3.60 min, 50.0% (A): 50.0% (B); 4.00 min, 50.0% (A): 50.0% (B); 4.30 min, 20.0% (A): 80.0% (B); 4.75 min, 20.0% (A) 80.0% (B); 4.85 min, 97.5% (A): 2.5% (B)

Triple-quadrupole mass spectrometer

PP

Biological

Gradient

[115]

Haloperidol, olanzapine, quetiapine, fluoxetine, paroxetine, bromazepam, lorazepam, risperidone and benzodiazepines

HSS T3

Acetonitrile (A) and 0.1% formic acid in water (B) 0–1 min, 75% (B); 1–6 min, 75–40%(B); 6 min, 75% (B)

Triple-quadrupole mass spectrometer

SPE

Biological

Gradient

[116]

Oxcarbazepine

BEH C18

Acetonitrile–10 mM ammonium acetate (85:15% v/v)

Triple-quadrupole mass spectrometer

SPE

Biological

Isocratic

[117]

Benzodiazepine 21

BEH C18

0.1% Formic acid in water (A) and 0.1% formic acid in Methanol (B). 70% A–30% B, ramping to 65%

B over 2.5 min, 70% B over 0.75 min, 77% B over 0.75 min, then to 95% B over 0.05 min and holding at 95% B for 1 min, returning to 30% B and re-equilibrating for 2 min

Mass detector

LLE

Biological

Gradient

[118]

Aripiprazole

Agilent Eclipse Plus C18

(A) 0.1% Formic acid aqueous and (B) acetonitrile. 0–1.2 min, 10–40% (B); 1.2–1.6 min, 40–100% (B); 1.6–1.9 min, 100% (B); 1.91–2.0 min, 10% (B)

Mass detector

SPE

Biological

Gradient

[119]

CNS

Levodopa, Carbidopa

BEH C18

(A) 5 mM Ammonium formate/formic acid at 1000/1 (v/v) and (B) acetone. 0.2 min, 25% (B); 0.2–1.8 min, 25–50% (B); 90% (B) for 0.9 min

Triple-quadrupole and electro chemical

PP

Biological

Gradient

[120]

Acetylcholine, histamine (HA)

BEH HILIC column

(A) 0.2% Formic acid and 20 mM ammonium formate in Water (B) acetonitrile. 0 min, 90% (B); 0–1.25 min, 10–70% (B)

Triple-quadrupole mass spectrometer

PP

Metabolite

Gradient

[121]

Proton pump inhibitor

Esomeprazole, Rabeprazole and Levosulpiride

Hypersil gold C18

(A) 2 mM Ammonium formate in water and (B) acetonitrile. 0.01 min, 10% (B); 0.20 min, 10% (B); 0.50 min, 90% (B); 0.70 min, 90% (B); 0.80 min, 10% (B); 1.00 min, 10% (B)

Triple-quadrupole mass spectrometer

LLE

Biological

Gradient

[122]

Anti-tubercular

Ethambutol, isoniazid and rifampicin

HSS T3

Water: methanol (50: 50% v/v)

Quadrupole

PP

Biological

Isocratic

[123]

Vitamin

Thiamin, riboflavin, Flavin, adenine dinucleotide, nicotinamide, and pyridoxal

HSS T3

10 mM Ammonium formate (A) and acetonitrile (B). 0 min, 95% (A); 1 min, 65% (A); 2 min, 45% (A); 2.1–3 min, 5%

(A), 3.1–4 min, 95% (A)

Mass detector

LLE

Biological

Gradient

[124]

Uracil and dihydrouracil

HSS T3 column

(A) 0.1% (v/v) Formic acid in UPLC-grade water and (B) 0.1% (v/v) formic acid in UPLC-grade acetonitrile. 0–.0 min, 0% (B); 3.0–3.2 min, 0–90% (B); 3.2–3.7 min, 90% (B); 3.7–5 min, 0% (B)

Triple-quadrupole mass spectrometer

LLE

Biological

Gradient

[125]

Immunosuppressant

Tacrolimus

BEH C18

10 mM Ammonium acetate, pH 6.00, adjusted with Formic acid and methanol (5:95% v/v)

Triple quadrupole mass spectrometer

SPE

Biological

Isocratic

[126]

Typhaneoside and Isorhamnetin-3-O-Neohesperidoside

BEH C18

(A) Acetonitrile and water (containing 0.1% formic acid) (B) 0 min, 80% (A); 1.7 min, 68% (A); 3.2 min 30% (A); 4.0 min, 20% (A)

Mass detector

Pollen typhae extract

Biological

Gradient

[127]

Mycophenolic acid

BEH C18

Acetonitrile and 10 mM Ammonium formate, pH 3.0 (75:25% v/v)

Mass detector

PP

Biological

Isocratic

[128]

Anticoagulant

Warfarin

BEH C18

(A) 0.2% Formic acid and 1% acetonitrile in water; and (B) 0.2% formic acid in acetonitrile. 80–70% (A) in 1.5 min and then changed linearly to 35% A for another 1.5 min, and remained for a further 0.8 min before changing back to 80% (A)

Mass detector

PP

Biological

Gradient

[129]

Clopidogrel

BEH C18

Acetonitrile and water containing 0.15% formic acid (75: 25% v/v)

Triple-quadrupole mass spectrometer

LLE

Biological

Isocratic

[130]

Expectorant

Hupehenine

BEH C18

(A) 0.1% Formic acid and acetonitrile (B). 0–2.0 min, 40–90% (B); maintained for 90% (B) for 0.5 min, then decreased to 40% within 0.1 min, then maintained at 40% for 0.4 min

Triple-quadrupole mass spectrometer

LLE

Biological

Gradient

[102]

Multicomponent analysis of drug

Gestodene, Ethinyl estradiol

BEH C18

Water (A) and acetonitrile (B) (both containing 0.1% formic acid). 1.5 min, 70% (B); 70–98% (B) within 1.1 min and returned to 70% (B)

Quadrupole

LLE

Biological

Gradient

[131]

Liensinine, Isoliensinine, and Neferine

BEH C18

(A) Water with 0.1 formic acid and acetonitrile (B). 0–1.0 min, 15–90% (B); 1.0–1.8 min, 90% (B); 1.8–2.0 min, 90–15% (B)

Triple-quadrupole mass spectrometer

PP

Biological

Gradient

[132]

Pinaverium Bromide

BEH C18

Acetonitrile: 5 mM ammonium formate (80:20% v/v)

Triple-quadrupole mass spectrometer

PP

Biological

Isocratic

[133]

Pimpinellin, Isopimpinellin and Phellopterin

BEH C18

Methanol: ammonium acetate (65:35% v/v)

Triple-quadrupole mass spectrometer

LLE

Biological

Isocratic

[134]

Endocannabinoids

2-arachidonoyl glycerol (2AG), 1-arachidonoyl glycerol (1AG), and anandamide

BEH C18

(A) Water contained 2 mM ammonium acetate and (B) methanol and contained 2 mM ammonium acetate. 0.0–0.5 min, 75% (B); 0.5–5.0 min, 79% (B); 5.0–5.5 min, 90% (B); 5.5–6.5 min, 75% (B)

Tandem mass spectrometry

PP

Biological

Gradient

[135]

Paeoniflorin, albiflorin, ferulic acid, tetrahydropalmatine, protopine, typhaneoside, senkyunolide I

BEH C18

(A) 0.1% Formic acid and (B) acetonitrile. 0–1 min, 5–10% (B); 1–6 min, 10–30% (B); 6–7 min, 30–40% (B); 7–8 min, 40–95% (B); 8–10 min, 95–5% (B)

Triple-quadrupole mass spectrometer

PP

Biological

Gradient

[136]

Caffeine, Tolbutamide, Metoprolol, Dapsone

BEH HILIC C18

Acetonitrile: water containing 0.1% formic acid (15:85% v/v)

Triple-quadrupole mass spectrometer

LLE

Biological

Isocrati

[137]

Xylazine, Free Morphine, Codeine, 6 Acetylmorphine, Cocaine, Benzoylecgonine in Postmortem

HSS T3

0.1% Formic acid in water (A) and acetonitrile (B). 0 min, 90% (A): 10% (B); 0.48 min, 90% (A): 10% (B); 0.50 min, 100% (A): 0% (B); 0.60 min, 85% (A): 15% (B); 2.0 min, 66% (A): 34% (B); 2.10 min, 5% (A): 95% (B); 2.25 min, 90% (A): 10% (B); 2.50 min, 90% (A): 10%(B)

Triple-quadrupole mass spectrometer

SPE

Biological

Gradient

[138]

Bupropion, metroprolol, midazolam, phenacetin, omeprazole and tolbutamide

BEH C18

Acetonitrile (A) and water (B) (containing 0.1% formic acid)

0.3-1.8 min, 30-60% (A); increasing to 95% over 0.2-0.5 min, then decreased to 30% within 0.1 min, and maintained at 30% for 0.4 min.

Triple-quadrupole mass spectrometer

PP

Biological

Gradient

[139]

Ketoconazole and Voriconazole on the Pharmacokinetics of Oxcarbazepine

BEH C18

Acetonitrile (A) and water (B) (containing 0.1% formic acid) 0–1 min, 20–80% (A); 1–1.5 min, 80–80% (A), 1.5–2 min 80–95% (A); 2–2.5 min, 95–95% (A); 2.5–2.6 min, 95–20% (A)

Triple-quadrupole mass Spectrometer

PP

Metabolite

Gradient

[140]

Neochlorogenic acid, chlorogenic acid, cryptochlorogenic acid, and geniposide

BEH C18

0.2% Acetic acid and methanol. 0–4.50 min, 15–30% (B); 4.50–5.50 min, 30–65% (B); 5.50–6.00 min, 65–15% (B); 6.00–7.50 min, 15–15% (B)

Triple-quadrupole mass Spectrometer

PP

Biological

Gradient

[141]

Evodiamine and Rutaecarpine

BEH C18

Acetonitrile (A) and water (B) both containing 0.2% Formic acid. 0 min, 40% (A): 60% (B); 0–0.6 min, 70% (A): 30% (B); 0.6–1.0 min, 70% (A): 30% (B); then returned to 40% (A):/60% (B)

Triple-quadrupole mass Spectrometer

LLE

Biological

Gradient

[142]

Bosentan and glimepiride

BEH C18

(A) 0.1% Formic acid in water and (B) acetonitrile. 0–0.5 min, 35% (B); 0.5–1.0 min, 35–80% (B); 1.0–1.5 min, 80–35% (B)

Triple-quadrupole

PP

Biological

Gradient

[143]

Amoxicillin and prednisolone

BEH C18

0.1% Formic acid in water (A) and 0.1% formic acid in acetonitrile (B). 0–1 min, 98% (A); 1–1.5 min, 98–15% (A); 1.5–2.5 min, 15% (A); 2.5–3.0 min, 15–2% (A); 3.0–3.5 min, 2–98% (A); 3.5–5.5 min, 98% (A)

Triple-quadrupole mass Spectrometer

SPE

Biological

Gradient

[144]

Fenofibric acid and berberine

Eclipse XDB C18 column

(A) Acetonitrile and (B) water (containing 0.1% formic acid). 0.0 min, 30 % (A): 70% (B); 0.3 min, 30% (A): 70% (B); 0.5 min, 50% (A): 50% (B); 1.0 min, 90% (A): 10% (B); 2.5 min, 90% (A): 10% (B); 2.6 min, 30% (A): 70% (B); 3.0 min, 30% (A): 70% (B)

Triple-quadrupole mass Spectrometer

LLE

Biological

Gradient

[145]