| Abstract | Uvod: Karbamazepin je antiepileptik s uskim terapijskim rasponom pa je nužno njegovo terapijsko praćenje. Metabolizira se u aktivni metabolit karbamazepin-10,11-epoksid, koji ima antiepileptična svojstva slična karbamazepinu. Na koncentraciju lijeka i metabolita utječu brojni čimbenici, među kojima su najvažniji komedikacija lamotriginom i/ili valproičnom kiselinom te renalna insuficijencija. Za mjerenje koncentracije karbamazepina koriste se imunokemijske ili kromatografske tehnike. Cilj istraživanja: Cilj rada bio je usporediti CMIA metodu za određivanje koncentracije karbamazepina s metodom LC-MS/MS. Ispitanici i metode: Istraživanjem je uspoređeno 54 rezultata mjerenja koncentracije karbamazepina pacijenata zaprimljenih u ZKLD KBCO. Prosječna dob ispitanika bila je 30 godina te su jednako bila zastupljena oba spola. Venska krv uzorkovana im je natašte, prije uzimanja sljedeće doze lijeka, u epruvetu s aktivatorom zgrušavanja, a dobiveni serum je analiziran kromatografskom metodom na LCMS/MS-8040 instrumentu (Shimadzu, Kyoto, Japan) te CMIA metodom na Arhitect i1000SR instrumentu (Abbott Laboratories, Lake Forest, SAD). Rezultati: Rezultati su obrađeni statističkim programom MedCalc. Kolmorogov-Smirnovljevim testom utvrđena je normalnost raspodjele podataka. Pearsonov koeficijent korelacije pokazao je izvrsnu međusobnu povezanost mjerenja (r=0,960; P<0,001; 95%CI 0,932-0,977). Passing-Bablok regresijska analiza vrijednosti mjerenja dobivenih LCMS/MS i CMIA metodama rezultirale su jednadžbom pravca: y=−0,52(95%CI -2,59 - 1,57)+0,89(95%CI 0,82 - 0,98)x iz koje je vidljivo da postoji proporcionalna razlika među izmjerenim vrijednostima. Rezultat Cusum testa pokazuje da nema značajnog odstupanja od linearnosti (P=0,92). Srednja razlika dvaju mjerenja iznosila je 3,5 ±1,41 μmol/L. Prosječni udio karbamazepin-10,11-epoksida iznosio je 13 % (6,1 do 24 %). Zaključak: CMIA metoda na instrumentu Architect i1000SR pokazala se pouzdanom i prikladnom za rutinsko određivanje koncentracije karbamazepina. Uspoređivane metode nisu podudarne i ne mogu se koristiti naizmjenično, nego se treba odlučiti kojom će se metodom pratiti pacijent. |
| Abstract (english) | Introduction: Carbamazepine is an anti-epileptic drug with a small therapeutic window therefore therapeutic drug monitoring is necessary. It metabolizes into the active metabolite carbamazepine-10,11-epoxide that has anti-epileptic properties similar to those of carbamazepine. Many factors affect the concentration of the drug and metabolite; the most significant include valproate-lamotrigine co-medication and renal insufficiency. The concentration of carbamazepine is measured using immunochemical or chromatographic techniques. Research objective: The objective of this research is to present a comparison of the CMIA method for determining carbamazepine concentrations with the LC-MS/MS method. Research subjects and methods: The research conducted a comparison of 54 results of carbamazepine concentration measurement of patients admitted to the Institute of Clinical Laboratory Diagnostics, Osijek University Hospital. The average age of the subjects was 30 years; both sexes equally represented. Venous blood samples were taken in fasting state, before taking the next dose of the drug, using a tube containing a clot activator and subsequently analyzed using the chromatographic technique on the instrument LCMS/MS-8040 (Shimadzu, Kyoto, Japan) and also the CMIA method on the instrument Arhitect i1000SR (Abbott Laboratories, Lake Forest, USA). Results: The results were analyzed using the statistical software MedCalc. The Kolmogorov-Smirnov test revealed a normal distribution of data. The Pearson correlation coefficient showed excellent association between measurements (r=0,960; P<0,001; 95%CI 0,932-0,977). The Passing-Bablok regression method of analysis applied to the measurement results obtained with the LCMS/MS and CMIA methods determined this linear equation: y=−0,52(95%CI -2,59 - 1,57)+0,89(95%CI 0,82 - 0,98)x which shows proportional differences between the measured values. The results of the Cusum test show no significant deviation from linearity (P=0,92). The mean difference between the two measurements was 3,5 ±1,41 μmol/L. The average level of carbamazepine-10,11-epoxide was 13 % (6,1 do 24 %). Conclusion: The CMIA method performed on the Architect i1000SR is shown to be reliable and suitable for routine determination of carbamazepine concentration. The compared methods do not coincide and cannot be used interchangeably, the method of choice should be used consistently in monitoring the patient. |
