Duloxetine ((γS)-N-methyl-γ-(1-naphthalenyloxy)-2-thiophenepropanamine, DLX) is the most recent antidepressants introduced onto the Italian market. Like venlafaxine and milnacipran, it acts as a dual serotonin and norepinephrine reuptake inhibitor (SNRI), with approximately equal potency at both transporters; DLX seems to be very efficient and to have a fast onset of action. DLX (Cymbalta®, Xeristar®, Yentreve®, Ariclaim®) is administered as enteric-coated pellets in capsules containing 20, 30 or 60 mg of active principle. The most usual dose for the treatment of depression is 60 mg/day, with a maximum suggested dose of 120 mg/day. The most common side effects are nausea, dry mouth, fatigue, insomnia, sedation, dizziness, constipation, increased sweating, increased blood pressure, decreased appetite and body weight. Furthermore, DLX overdose can present worrisome effects, such as signs of altered mental status, cardiovascular alterations with hypotension, sinus bradycardia and prolonged QTc interval. It is evident that there is a need for having on hand new, reliable analytical methods for the determination of DLX plasma levels in depressed patients. An original HPLC method coupled to solid-phase extraction (SPE) for the determination of DLX plasma levels has been developed. It is based on the use of a Genesis C8 column (150×4.6 mm I.D., 5 μm) as the stationary phase and a mixture of acetonitrile and a pH 3.0 phosphate buffer containing triethylamine (40/60, v/v) as the mobile phase. UV detection is carried out at 230 nm. Using loxapine as the Internal Standard (IS), a chromatographic run lasts 5 minutes. The sample pre-treatment employs mixed mode reversed phase – cation exchange (MCX) cartridges (30 mg, 1 mL) and only 450 µL of human plasma are needed for a complete analysis. Cartridge elution is carried out with methanol, which is then dried and redissolved in 150 µL of mobile phase, thus obtaining a threefold concentration of the analytes. Extraction yields are satisfactory, always higher than 90%. Good linearity (r2 > 0.9990) has been found in the 2-200 ng/mL DLX concentration range. Precision assays are also satisfactory, with RSD% values always lower than 5%. The method seems to be suitable for the TDM of DLX in depressed patients' plasma.

HPLC analysis of the recent SNRI drug duloxetine in plasma of depressed patients

MERCOLINI, LAURA;MANDRIOLI, ROBERTO;SARACINO, MARIA ADDOLORATA;GHEDINI, NADIA;RAGGI, MARIA AUGUSTA
2007

Abstract

Duloxetine ((γS)-N-methyl-γ-(1-naphthalenyloxy)-2-thiophenepropanamine, DLX) is the most recent antidepressants introduced onto the Italian market. Like venlafaxine and milnacipran, it acts as a dual serotonin and norepinephrine reuptake inhibitor (SNRI), with approximately equal potency at both transporters; DLX seems to be very efficient and to have a fast onset of action. DLX (Cymbalta®, Xeristar®, Yentreve®, Ariclaim®) is administered as enteric-coated pellets in capsules containing 20, 30 or 60 mg of active principle. The most usual dose for the treatment of depression is 60 mg/day, with a maximum suggested dose of 120 mg/day. The most common side effects are nausea, dry mouth, fatigue, insomnia, sedation, dizziness, constipation, increased sweating, increased blood pressure, decreased appetite and body weight. Furthermore, DLX overdose can present worrisome effects, such as signs of altered mental status, cardiovascular alterations with hypotension, sinus bradycardia and prolonged QTc interval. It is evident that there is a need for having on hand new, reliable analytical methods for the determination of DLX plasma levels in depressed patients. An original HPLC method coupled to solid-phase extraction (SPE) for the determination of DLX plasma levels has been developed. It is based on the use of a Genesis C8 column (150×4.6 mm I.D., 5 μm) as the stationary phase and a mixture of acetonitrile and a pH 3.0 phosphate buffer containing triethylamine (40/60, v/v) as the mobile phase. UV detection is carried out at 230 nm. Using loxapine as the Internal Standard (IS), a chromatographic run lasts 5 minutes. The sample pre-treatment employs mixed mode reversed phase – cation exchange (MCX) cartridges (30 mg, 1 mL) and only 450 µL of human plasma are needed for a complete analysis. Cartridge elution is carried out with methanol, which is then dried and redissolved in 150 µL of mobile phase, thus obtaining a threefold concentration of the analytes. Extraction yields are satisfactory, always higher than 90%. Good linearity (r2 > 0.9990) has been found in the 2-200 ng/mL DLX concentration range. Precision assays are also satisfactory, with RSD% values always lower than 5%. The method seems to be suitable for the TDM of DLX in depressed patients' plasma.
Atti del XVIII Convegno Nazionale della Divisione di Chimica Farmaceutica della Società Chimica Italiana
117
117
L. Mercolini; R. Mandrioli; M.A. Saracino; N. Ghedini; R. Cazzolla; M. Amore; M.A. Raggi
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/11585/49376
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