DEVELOPMENT AND VALIDATION OF A NEW UHPLC-DAD APPROACH FOR ATOMOXETINE DETECTION IN SEVERAL MEDICINAL PLANTS

Abstract

Objective: Atomoxetine (ATX) is a medication that is extensively used to treat attention deficit hyperactivity disorder in children, adolescents, and adults. The goal of this work was to create a speedy, easy, and sensitive ultra high performance liquid chromatographic method (UHPLC) for the measurement of atomoxetine in various medicinal plants. (Salvia officinalis L., Rosmarinus officinalis L., Melissa officinalis L., Ginkgo biloba L.). Material and Method: Prior to chromatographic separation, liquid-liquid extraction was applied, which is currently the preferred extraction technique due to its simple, fast and efficient procedure for sample preparation. The chromatographic separation was achieved by reversed phase C18 (5 μm × 4.6 mm × 150 mm) analytical column and a mobile phase consisting of monobasic potassium dihydrogen orthophosphate (pH=6.8) and acetonitrile (50:50 v/v) at flow rate of 0.8 ml/min and diode array detector (DAD) detecting at 215±2 nm. Result and Discussion: The envisioned method's linear behavior was tested in the 0.5-20 μg/ml range (r2=0.09990). In compliance with International Conference on Harmonisation (ICH) criteria, the method received validation by means of accuracy, precision, repeatability, specificity, robustness, and detection and quantification boundaries. LOD and LOQ values were determined as 0.16 and 0.5 μg/ml. RSD values for hourly and daily measurements are found to be below 2.5% for both assays. The proposed method can be used effectively for quantification of atomoxetine in medicinal and aromatic plants. The proposed analytical procedure represents an efficient method for the quantification and routinee analysis of atomoxetine in medicinal and aromatic plants.

Keywords

• Atomoxetine
• attention deficit hyperactivity disorder
• diode array detector (DAD)
• medicinal plants
• ultra high performance liquid chromatography (UHPLC)

BAZI TIBBİ BİTKİLERDE ATOMOKSETİN TAYİNİ İÇİN YENİ BİR UHPLC-DAD YÖNTEMİNİN GELİŞTİRİLMESİ VE VALİDASYONU

Abstract

Amaç: Atomoksetin (ATX) çocuklarda, ergenlerde ve yetişkinlerde dikkat eksikliği hiperaktivite bozukluğunun tedavisinde yaygın olarak kullanılmaktadır. Bu çalışmada, bazı tıbbi bitkilerde (Salvia officinalis L., Rosmarinus officinalis L., Melissa officinalis L., Ginkgo biloba L.) atomoksetin analizi için hızlı, basit ve hassas bir ultra yüksek performanslı sıvı kromatografik yöntem (UHPLC) geliştirilmesi amaçlanmıştır. Gereç ve Yöntem: Kromatografik ayırmadan önce, numune hazırlama için basit, hızlı ve verimli prosedürü nedeniyle günümüzde tercih edilen ekstraksiyon tekniği olan sıvı-sıvı ekstraksiyonu uygulanmıştır. Kromatografik ayırma, ters fazlı C18 (5 μm × 4.6 mm × 150 mm) analitik kolon ve monobazik potasyum dihidrojen ortofosfat (pH=6.8) ve asetonitrilden (50:50 h/h) oluşan bir mobil fazda 0.8 ml/dk akış hızında ve 215±2 nm’de diyot dizisi dedektörü (DAD) tespiti ile sağlandı. Sonuç ve Tartışma: Önerilen yöntemin doğrusallığı 0.5-20 μg/ml (r2=0.9990) aralığında incelenmiştir. Yöntem, Uluslararası Uyumlaştırma Konferansı (ICH) yönergelerine uygun olarak doğruluk, kesinlik, tekrarlanabilirlik, özgüllük, sağlamlık ve dedeksiyon ve kantitasyon limitleri açısından doğrulanmıştır. LOD ve LOQ sırasıyla 0.16 ve 0.5 μg/ml olarak bulundu. Gün içi ve günler arası RSD değerleri her iki test için de %2.5’in altındadır. Önerilen yöntem, tıbbi ve aromatik bitkilerde atomoksetin miktarının belirlenmesi için etkin bir şekilde kullanılabilir. Önerilen analitik prosedür, tıbbi ve aromatik bitkilerde atomoksetinin miktarının belirlenmesi ve rutin analizi için etkili bir yöntemi temsil eder.

Keywords

• Atomoksetin
• dikkat eksikliği hiperaktivite bozukluğu
• diyot dizisi dedektörü (DAD)
• tıbbi bitkiler
• ultra yüksek performanslı sıvı kromatografisi (UHPLC)

References

1. 1. Dulcan, M. (1997). Practie parameters for the assesment and treatment of children, adolescents, and adults with attention-deficit/hyperactivity disorder. Journal of the American Academy of Child & Adolescent Psychiatry, 36(10), 85-121. [CrossRef]
2. 2. Polanczyk, G., Lima, M.S., Horta, B.L., Biedermen, J., Rohde, L.A. (2007). The worldwide prevalence of ADHD: A systematic review and meta-regression analysis. American Journal of Psychiatry, 164(6), 942-948. [CrossRef]
3. 3. Baughman, F.A. (1999). Treatment of attention-deficit/hyperactivity disorder. JAMA, 281, 780-788.
4. 4. Corman, S.L., Fedutes, B.A., Culley, C.M. (2004). Atomoxetine: The first nonstimulant for the management of attention-deficit/hyperactivity disorder. American Journal Health-System Pharmacy, 61(22), 2391-2399. [CrossRef]
5. 5. Michelson, D., Adler, L., Spencer, T., Reimher F.W., West, S.A., Allen, A.J., Kelsey, D., Wernicke, J., Dietrich, A., Milton, D. (2003). Atomoxetine in adults with ADHD: Two randomized placebo controlled studies. Biological Psychiatry, 53(2), 112-120. [CrossRef]
6. 6. Davids, E., Gastpar, M. (2004). Atomoxetine for the treatment of attention deficit/hyperactivity disorder. Fortschr Neurol Psychiatr, 72(10), 586-591. [CrossRef]
7. 7. Christman, A.K., Fermo, J.D., Markowitz, J.S. (2004). Atomoxetine, a novel treatment for attention deficit hyperactivity disorder. Pharmacotherapy: The Journal of Human Pharmacology and Drug Therapy, 24(8), 1020-1036. [CrossRef]
8. 8. Sauer, J.M., Ponsler, G.D., Mattiuz, E.L., Long, A.J., Witcher, J.W., Thomasson, H.R., Desante, K.A. (2003). Disposition and metabolic fate of atomoxetine hydrochloride: The role of CYP2D6 in human disposition and metabolism. Drug Metabolism and Disposition, 31(1), 98-107. [CrossRef]

9. 9. Kumar, S.A. (2009). Plants-based Medicines in India. http://pib.nic.in/feature/feyr2000/fmay2000/f2405 20006.html. Access date: 06.06.2010.
10. 10. Farid, N.A., Bergstrom, R.F., Ziege, E.A., Parli, C.J., Lemberger, L. (1985). Single-dose and steady-state pharmacokinetics of tomoxetine in normal subjects. Journal of Clinical Pharmacology, 25(4), 296-301. [CrossRef]
11. 11. Mullen, J.H., Shugert, R.L., Ponsler, G.D., Li, Q., Sundaram, B., Coales, H.L., Yakupkovic, J.E., Lelacheur, R.M., Wheeler, W.J., Belas, F.J., Sauer, J-M. (2005). Simultaneous quantification of atomoxetine as well as its primary oxidative and O-glucuronide metabolites in human plasma and urine using liquid chromatography tandem mass spectrometry (LC-MS/MS). Journal of Pharmaceutical and Biomedical Analysis, 38(4), 720-733. [CrossRef]
12. 12. Patel, C., Patel M., Rani, S., Nivsarkar, M., Padh, H. (2007). A new high performance liquid chromatographic method for quantification of atomoxetine in human plasma and its application for pharmacokinetic study. Journal of Chromatography B, 850(1-2), 356-360. [CrossRef]
13. 13. The International Conference on Harmonisation (ICH). (2005). ICH Technical Requirements for Registration of Pharmaceuticals for Human Use on validation of analytical procedures Q2A. IFPM, Genava.
14. 14. Ceylan, B., Tırıs, G., Tekkeli, S.E.K. (2021). A new HPLC method with UV detection for the determination of carnosol in human plasma and application to a pharmacokinetic study. Chromatographia, 84(9), 855-860. [CrossRef]