Öz
ABSTRACT
A combination of levetiracetam (LEV) and carbamazepine (CBZ) may be used to
obtain synergistic effect in treatment of epilepsy. The aim of the study is to develop and
validate a simple reversed phase (RP) HPLC-UV method to determine simultaneously
LEV and CBZ in pure form and in different pharmaceutical formulations. Separation
was achieved on a C18 column (5 μm, 4.6 mm×250 mm) using a mobile phase
consisting of methanol and ultrapure water (45:55, v/v) at a flow rate of 1.0 mL/min
at 230 nm. Validation parameters (specificity, linearity, accuracy, precision, LOD and
LOQ) were studied according to the relevant ICH Guideline. The calibration curves
were linear over a concentration range of 0.5-32 μg/mL for both LEV and CBZ. The
intra- and inter-day accuracy values (as relative error; RE) were less than ±2% and also
the intra- and inter-day precision values (as the percent relative standard deviation;
RSD%) were less than 2%. According to relevant guidelines, the accuracy and precision
of the developed method is suitable. LOD and LOQ values were found to be 0.036 and
0.110 μg/mL for LEV and 0.026 and 0.078 μg/mL for CBZ, respectively. The simple,
specific, accurate, precise and sensitive analytical method developed could be useful for
simultaneous determination of LEV and CBZ.
Keywords: Carbamazepine, HPLC-UV method, Levetiracetam, Validation.
ÖZET
Epilepsi tedavisinde sinerjik etki elde etmek için levetirasetam (LEV) ve karbamazepin
(CBZ) birarada kullanılabilir. Bu çalışmanın amacı, saf halde ve farklı farmasötik
formülasyonlarda LEV ve CBZ’yi eş zamanlı olarak belirlemek üzere basit ters faz
(RP) HPLC-UV yönteminin geliştirilmesi ve geçerliliğinin gösterilmesidir. Ayırım, C18
kolonunda (5 μm, 4.6 mm x 250 mm), metanol ve ultra saf sudan (45:55, h/h) oluşan
hareketli faz kullanılarak 1.0 mL/dk akış hızında ve 230 nm’de gerçekleştirilmiştir.
Geçerlilik parametreleri (özgüllük, doğrusallık, doğruluk, kesinlik, LOD ve LOQ) ilgili
ICH Kılavuzuna göre çalışılmıştır Kalibrasyon eğrileri hem LEV hem de CBZ için
0.5-32 μg/mL derişim aralığında doğrusal olarak bulunmuştur. Gün içi ve günler arası
doğruluk değerlerinin [bağıl hata (BH) olarak] ±%2’den az ve gün içi ve günler arası
kesinlik değerlerinin de [% bağıl standart sapma; %BSS) %2’den az olduğu saptanmıştır.
İlgili kılavuzlara göre, geliştirilen yöntemin doğruluğu ve kesinliği uygundur. LOD ve
LOQ değerleri sırasıyla, LEV için 0.036 ve 0.110 μg/mL ve CBZ için sırasıyla 0.026
ve 0.078 μg/mL olarak bulunmuştur. Geliştirilen basit, özgül, doğru, kesin ve hassas
analitik yöntem LEV ve CBZ’nin eş zamanlı olarak saptanması için faydalı olabilir.
Anahtar Kelimeler: Geçerlilik, HPLC-UV yöntemi, Karbamazepin, Levetirasetam
Anahtar Kelimeler
Kaynakça
- REFERENCES1. Akdağ G, Algın İ, Erdinç O: Epilepsi. Osmangazi Tıp Dergisi 2016, 38(1):35–41.
- 2. Aktekin B, Ağan K, Arman F, Aslan K, Aykutlu E, Baklan B, Baykan B, Bebek N, Bilir E, Bora İ, Bozdemir H, Gürses C, Kayrak N, Özkara Ç, Saygı S, Velioğlu S: Epilepsi rehberi, Epilepsi 2012, 18(1): 26-38.
- 3. Cankurtaran EŞ, Uluǧ B, Saygi S: Epilepsiye eşlik eden psikiyatrik bozukluklar. Klinik Psikofarmakoloji Bülteni 2004, 14(2):97–106.
- 4. Toklu Z: Epilepside tedavi stratejileri. Kocatepe Tıp Dergisi 2015, 16:147–150.
- 5. Mani J: Combination therapy in tpilepsy: what, when, how and what not!. Journal of the Association of Physicians of India 2013, 61(8):40–44.
- 6. Brodie MJ, Sills GJ: Combining antiepileptic drugs - rational polytherapy?. Seizure 2011: 369–375.
- 7. Florek-Luszczki M, Wlaz A, Luszczki JJ: Interactions of levetiracetam with carbamazepine, phenytoin, topiramate and vigabatrin in the mouse 6Hz psychomotor seizure model – a type II isobolographic analysis. European Journal of Pharmacology 2014, 723:410–418.
- 8. Bianchi V, Arfini C, Vidali M: Therapeutic drug monitoring of levetiracetam: comparison of a novel immunoassay with an HPLC method. Therapeutic Drug Monitoring 2014, 36(5): 681–685.
- 9. Contin M, Mohamed S, Albani F, Riva R, Baruzzi A: Simple and validated HPLC-UV analysis of levetiracetam in deproteinized plasma of patients with epilepsy. Journal of Chromatography B 2008, 873(1):129–132.
- 10. Shah JS, Vidyasagar G, Barot H: Stability indicating RP-HPLC method for estimation of levetiracetam in pharmaceutical formulation and application to pharmacokinetic study. Der Pharmacia Sinica 2012, 3(5): 576-589.
- 11. Petruševska M, Berglez S, Krisch I, Legen I, Megušar K, Peternel L, Abrahamsson B, Cristofoletti R, Groot DW, Kopp S, Langguth P, Mehta M, Polli JE, Shah VP, Dressman J: Biowaiver monographs for immediate release solid oral dosage forms: levetiracetam. Journal of Pharmaceutical Sciences 2015, 104(9):2676–2687.
- 12. Sweetman SC. Martindale: The Complete Drug Reference. The Pharmaceutical Press; London, UK, 2009.
- 13. Czapinski P, Blaszczyk B, Czuczwar SJ: Mechanisms of action of antiepileptic drugs. Current Topics in Medicinal Chemistry 2005, 5:3–14.
- 14. Naima Z, Siro T, Juan-Manuel GD, Chantal C, René C, Jerome D: Interactions between carbamazepine and polyethylene glycol (PEG) 6000: characterisations of the physical, solid dispersed and eutectic mixtures. European Journal of Pharmaceutical Sciences 2001, 12(4):395–404.
- 15. European Pharmacopoeia (9th edition), European Directorate for the Quality of Medicines&HealthCare, Council of Europe, Strasbourg, France. 2017.
- 16. Mowafy HA, Alanazi FK, El Maghraby GM: Development and validation of an HPLC-UV method for the quantification of carbamazepine in rabbit plasma. Saudi Pharmaceutical Journal 2012, 20(1):29–34.
- 17. Convention, T. U. S. United States Pharmacopeia (USP30-NF25); 2007.
- 18. Sultana S, Halder S, Kabir AKL, Rouf ASS: Effect of solubility enhancers on the release of carbamazepine from hydrophilic polymer based matrix tablet. Dhaka University Journal of Pharmaceutical Sciences 2014, 13(2):167–173.
- 19. Can NO, Arli G: Reversed-phase HPLC analysis of levetiracetam in tablets using monolithic and conventional C18 silica column. Journal of AOAC International 2010, 93(4):1077–1085.
- 20. Devanaboyina N, Satyanarayana T, Rao BG: A novel RP-HPLC method for the analysis of levetiracetam in formulations. Der Pharma Chemica 2011, 3(6):112–117.
- 21. Skopp G, Schmitt HP, Pedal I: Fulminant liver failure in a patient on carbamazepine and levetiracetam treatment associated with status epilepticus. Archive für Kriminologie 2006, 217(5–6): 161–175.
- 22. Ibrahim FA, El-Yazbi AF, Barary MA, Wagih MM: Sensitive inexpensive HPLC determination of four antiepileptic drugs in human plasma: application to PK studies. Bioanalysis 2016, 8(21): 2219–2234.
- 23. Karinen R, Vindenes V, Hasvold I, Olsen KM, Christophersen AS, Øiestad E: Determination of a selection of anti-epileptic drugs and two active metabolites in whole blood by reversed phase UPLC-MS/MS and some examples of application of the method in forensic toxicology cases. Drug Testing and Analysis 2015, 7(7):634–644.
- 24. ICH Topic Q 2 (R1) Validation of Analytical Procedures: Text and Methodology.; 2018 July 7. Available from: http://www.ema.europa.eu/docs/en_GB/document_library /Scientific_guideline/2009/09/WC500002662.pdf [Website].
- 25. Hussien EM: HPLC method validation for modernization of the tetracycline hydrochloride capsule USP Monograph. Bulletin of Faculty of Pharmacy, Cairo University 2014, 52(2): 239–244.
- 26. Shabir GA: Validation of high-performance liquid chromatography methods for pharmaceutical analysis. Journal of Chromatography A 2003, 987(1–2):57–66.
- 27. Urban MCC, Mainardes RM, Gremião MPD: Development and validation of HPLC method for analysis of dexamethasone acetate in microemulsions. Brazilian Journal of Pharmaceutical Sciences 2009, 45(1):87–92.
Öz
Kaynakça
- REFERENCES1. Akdağ G, Algın İ, Erdinç O: Epilepsi. Osmangazi Tıp Dergisi 2016, 38(1):35–41.
- 2. Aktekin B, Ağan K, Arman F, Aslan K, Aykutlu E, Baklan B, Baykan B, Bebek N, Bilir E, Bora İ, Bozdemir H, Gürses C, Kayrak N, Özkara Ç, Saygı S, Velioğlu S: Epilepsi rehberi, Epilepsi 2012, 18(1): 26-38.
- 3. Cankurtaran EŞ, Uluǧ B, Saygi S: Epilepsiye eşlik eden psikiyatrik bozukluklar. Klinik Psikofarmakoloji Bülteni 2004, 14(2):97–106.
- 4. Toklu Z: Epilepside tedavi stratejileri. Kocatepe Tıp Dergisi 2015, 16:147–150.
- 5. Mani J: Combination therapy in tpilepsy: what, when, how and what not!. Journal of the Association of Physicians of India 2013, 61(8):40–44.
- 6. Brodie MJ, Sills GJ: Combining antiepileptic drugs - rational polytherapy?. Seizure 2011: 369–375.
- 7. Florek-Luszczki M, Wlaz A, Luszczki JJ: Interactions of levetiracetam with carbamazepine, phenytoin, topiramate and vigabatrin in the mouse 6Hz psychomotor seizure model – a type II isobolographic analysis. European Journal of Pharmacology 2014, 723:410–418.
- 8. Bianchi V, Arfini C, Vidali M: Therapeutic drug monitoring of levetiracetam: comparison of a novel immunoassay with an HPLC method. Therapeutic Drug Monitoring 2014, 36(5): 681–685.
- 9. Contin M, Mohamed S, Albani F, Riva R, Baruzzi A: Simple and validated HPLC-UV analysis of levetiracetam in deproteinized plasma of patients with epilepsy. Journal of Chromatography B 2008, 873(1):129–132.
- 10. Shah JS, Vidyasagar G, Barot H: Stability indicating RP-HPLC method for estimation of levetiracetam in pharmaceutical formulation and application to pharmacokinetic study. Der Pharmacia Sinica 2012, 3(5): 576-589.
- 11. Petruševska M, Berglez S, Krisch I, Legen I, Megušar K, Peternel L, Abrahamsson B, Cristofoletti R, Groot DW, Kopp S, Langguth P, Mehta M, Polli JE, Shah VP, Dressman J: Biowaiver monographs for immediate release solid oral dosage forms: levetiracetam. Journal of Pharmaceutical Sciences 2015, 104(9):2676–2687.
- 12. Sweetman SC. Martindale: The Complete Drug Reference. The Pharmaceutical Press; London, UK, 2009.
- 13. Czapinski P, Blaszczyk B, Czuczwar SJ: Mechanisms of action of antiepileptic drugs. Current Topics in Medicinal Chemistry 2005, 5:3–14.
- 14. Naima Z, Siro T, Juan-Manuel GD, Chantal C, René C, Jerome D: Interactions between carbamazepine and polyethylene glycol (PEG) 6000: characterisations of the physical, solid dispersed and eutectic mixtures. European Journal of Pharmaceutical Sciences 2001, 12(4):395–404.
- 15. European Pharmacopoeia (9th edition), European Directorate for the Quality of Medicines&HealthCare, Council of Europe, Strasbourg, France. 2017.
- 16. Mowafy HA, Alanazi FK, El Maghraby GM: Development and validation of an HPLC-UV method for the quantification of carbamazepine in rabbit plasma. Saudi Pharmaceutical Journal 2012, 20(1):29–34.
- 17. Convention, T. U. S. United States Pharmacopeia (USP30-NF25); 2007.
- 18. Sultana S, Halder S, Kabir AKL, Rouf ASS: Effect of solubility enhancers on the release of carbamazepine from hydrophilic polymer based matrix tablet. Dhaka University Journal of Pharmaceutical Sciences 2014, 13(2):167–173.
- 19. Can NO, Arli G: Reversed-phase HPLC analysis of levetiracetam in tablets using monolithic and conventional C18 silica column. Journal of AOAC International 2010, 93(4):1077–1085.
- 20. Devanaboyina N, Satyanarayana T, Rao BG: A novel RP-HPLC method for the analysis of levetiracetam in formulations. Der Pharma Chemica 2011, 3(6):112–117.
- 21. Skopp G, Schmitt HP, Pedal I: Fulminant liver failure in a patient on carbamazepine and levetiracetam treatment associated with status epilepticus. Archive für Kriminologie 2006, 217(5–6): 161–175.
- 22. Ibrahim FA, El-Yazbi AF, Barary MA, Wagih MM: Sensitive inexpensive HPLC determination of four antiepileptic drugs in human plasma: application to PK studies. Bioanalysis 2016, 8(21): 2219–2234.
- 23. Karinen R, Vindenes V, Hasvold I, Olsen KM, Christophersen AS, Øiestad E: Determination of a selection of anti-epileptic drugs and two active metabolites in whole blood by reversed phase UPLC-MS/MS and some examples of application of the method in forensic toxicology cases. Drug Testing and Analysis 2015, 7(7):634–644.
- 24. ICH Topic Q 2 (R1) Validation of Analytical Procedures: Text and Methodology.; 2018 July 7. Available from: http://www.ema.europa.eu/docs/en_GB/document_library /Scientific_guideline/2009/09/WC500002662.pdf [Website].
- 25. Hussien EM: HPLC method validation for modernization of the tetracycline hydrochloride capsule USP Monograph. Bulletin of Faculty of Pharmacy, Cairo University 2014, 52(2): 239–244.
- 26. Shabir GA: Validation of high-performance liquid chromatography methods for pharmaceutical analysis. Journal of Chromatography A 2003, 987(1–2):57–66.
- 27. Urban MCC, Mainardes RM, Gremião MPD: Development and validation of HPLC method for analysis of dexamethasone acetate in microemulsions. Brazilian Journal of Pharmaceutical Sciences 2009, 45(1):87–92.
Ayrıntılar
| Birincil Dil | İngilizce |
|---|---|
| Konular | Eczacılık ve İlaç Bilimleri |
| Bölüm | Research Articles |
| Yazarlar | |
| Yayımlanma Tarihi | 15 Haziran 2018 |
| Kabul Tarihi | 27 Kasım 2018 |
| Yayımlandığı Sayı | Yıl 2018 Cilt: 38 Sayı: 2 |