Abstract
Valproic acid is an anticonvulsant that requires careful therapeutic drug monitoring. Valproic acid is also used in psychiatric patients. Bayer Diagnostics (Tarrytown, NY) recently marketed a turbidimetric immunoassay for monitoring valproic acid concentrations in serum or plasma using the ADVIA® 1650 analyzer. We evaluated the performance of this new assay by comparing it with a widely used fluorescence polarization immunoassay (FPIA) on the AxSYM® analyzer (Abbott Laboratories, Abbott Park, IL). The total coefficient of variation (CV) for the low control of this new assay was 6.8% (mean=30.7, SD=2.1 µg/mL, n=44) while the corresponding CVs for the medium and high controls were 3.3% (mean=81.0, SD=2.7 µg/mL, n=44) and 5.9% (mean=142.9, SD=8.4 µg/mL, n=44), respectively. The assay is linear up to a serum valproic acid concentration of 170 µg/mL, and the detection limit is 4.4 µg/mL. We observed an excellent correlation between the FPIA of valproic acid and the turbidimetric assay using specimens from 52 different patients who were receiving valproic acid. Using the valproic acid concentrations obtained by the FPIA as the x‐axis, and the corresponding valproic acid concentrations obtained by the turbidimetric assay as the y‐axis, we developed the following regression equation: y=1.03 x+1.55 (r=0.98). With this new assay, high concentrations of bilirubin (unconjugated 30 mg/dL and conjugated 30 mg/dL) and gross hemolysis (4+, hemoglobin: 1,500 mg/dL) have no effect on measurements of valproic acid concentration. We conclude that the new turbidimetric assay for valproic acid can be used for routine therapeutic drug monitoring of valproic acid in clinical laboratories. J. Clin. Lab. Anal. 19:31–35, 2005. © 2005 Wiley‐Liss, Inc.
Keywords: valproic acid, turbidimetric assay, fluorescence polarization immunoassay
REFERENCES
- 1. Sato S, Wright DG, Penry JK, Dreifuss FE, Sackellares JC, Kupferberg HJ. Valproic acid versus ethosuximide in the treatment of absence seizure. Neurology 1982;32:157–163. [DOI] [PubMed] [Google Scholar]
- 2. Henriksen O, Johannessen SI. Clinical and pharmocokinetic observations on sodium valproate: a five‐year follow up study on 100 children with epilepsy. Acta Neurol Scand 1982;65:504–523. [DOI] [PubMed] [Google Scholar]
- 3. Bruni J, Albright P. Valproic acid therapy for complex partial seizures: its efficacy and toxic effects. Arch Neurol 1983;40:135–137. [DOI] [PubMed] [Google Scholar]
- 4. Lee K, Melchior JC. Sodium valproate versus phenobarbital in the prophylactic treatment of febrile convulsions in childhood. Eur J Pediatr 1983;137:151–153. [DOI] [PubMed] [Google Scholar]
- 5. Coppola G. Treatment of partial seizures in childhood: an overview. CNS Drugs 2004;18:133–156. [DOI] [PubMed] [Google Scholar]
- 6. Spina E, Perugi G. Antiepileptic drugs: indications other than epilepsy. Epileptic Disord 2004;6:57–75. [PubMed] [Google Scholar]
- 7. Asnis GM, Kohn SR, Henderson M, Brown NL. SSRIs versus non‐SSRIs in post‐traumatic stress disorders: an update with recommendations. Drugs 2004;64:383–404. [DOI] [PubMed] [Google Scholar]
- 8. Hosak L, Libiger J. Antiepileptic drugs in schizophrenia: a review. Eur Psychiatry 2002;17:371–378. [DOI] [PubMed] [Google Scholar]
- 9. Muller‐Oerlinghausen B, Berghofer A, Bauer M. Bipolar disorder. Lancet 2002;359:241–247. [DOI] [PubMed] [Google Scholar]
- 10. Irshaid YM, Hamadi AA, Al Homrany M. Evaluation of therapeutic drug monitoring of antiepileptic drugs. Int J Clin Pharmacol Ther 2003;41:126–131. [PubMed] [Google Scholar]
- 11. El Desoky ES, Al‐Ghamdi HA, Halaby FH, Al‐Beshri M. Therapeutic monitoring of digoxin and antiepileptic drugs in Egypt and Saudi Arabia. Ther Drug Monit 2003;25:211–214. [DOI] [PubMed] [Google Scholar]
- 12. Mino T, Nakajima M, Wakabayashi H, Yamato S, Shimada K. Determination of valproic acid in serum by liquid chromatography‐atmospheric pressure chemical ionization mass spectrometry. Anal Sci 2001;17:999–1001. [DOI] [PubMed] [Google Scholar]
- 13. Darius J, Meyer FP. Sensitive capillary gas chromatography‐mass spectrometric method for therapeutic drug monitoring of valproic acid and seven of its metabolites in human serum: applications of the assay for a group of pediatric epileptics. J Chromatogr B Biomed Appl 1994;656:343–351. [DOI] [PubMed] [Google Scholar]
- 14. Liu H, Forman LJ, Montoya J, Eggers C, Barham C, Delgado M. Determination of valproic acid by high performance liquid chromatography with photodiode array and fluorescence detection. J Chromatogr 1992;576:163–169. [DOI] [PubMed] [Google Scholar]
- 15. Steijns LS, Bouw J, van der Weide J. Evaluation of fluorescence polarization assay for measuring valproic acid, phenytoin, carbamazepine and phenobarbital in serum. Ther Drug Monit 2002;24:432–435. [DOI] [PubMed] [Google Scholar]