Development, validation and application of an HPLC-MS/MS method for the determination of fentanyl and nor-fentanyl in human plasma and saliva

Bista, S.R., Lobb, M., Haywood, A., Hardy, J., Tapuni, A. and Norris, R. (2014) Development, validation and application of an HPLC-MS/MS method for the determination of fentanyl and nor-fentanyl in human plasma and saliva. Journal of Chromatography B: Analytical Technologies in the Biomedical and Life Sciences, 960 27-33. doi:10.1016/j.jchromb.2014.04.019


Author Bista, S.R.
Lobb, M.
Haywood, A.
Hardy, J.
Tapuni, A.
Norris, R.
Title Development, validation and application of an HPLC-MS/MS method for the determination of fentanyl and nor-fentanyl in human plasma and saliva
Journal name Journal of Chromatography B: Analytical Technologies in the Biomedical and Life Sciences   Check publisher's open access policy
ISSN 1873-376X
1570-0232
Publication date 2014-06-01
Year available 2014
Sub-type Article (original research)
DOI 10.1016/j.jchromb.2014.04.019
Open Access Status Not yet assessed
Volume 960
Start page 27
End page 33
Total pages 7
Place of publication Amsterdam, NX, Netherlands
Publisher Elsevier
Language eng
Subject 1303 Specialist Studies in Education
1602 Criminology
1307 Cell Biology
1308 Clinical Biochemistry
Abstract Monitoring fentanyl concentration in saliva and plasma may be useful in pharmacokinetic/pharmacodynamic studies. Salivettes® have been used widely for collecting saliva samples. However due to its lipophilicity, fentanyl adsorbs to the cotton dental bud (CDB) used in this device. Furthermore, due to dry mouth being a common adverse effect seen in patients treated with opioids, obtaining enough saliva for analysis is often a challenge. Hence, a simple simultaneous method to quantify fentanyl and its metabolite in both human plasma and saliva was developed and validated. A novel extraction method was also developed and validated to recover fentanyl in saliva directly from the CDB. This extraction method utilises acetonitrile to recover the fentanyl directly from the CDB rather than recovery by centrifugation, which is not always possible. Reverse phase chromatographic separation was performed on a Shimadzu LC 20A HPLC system using gradient elution. The electrospray ion source (ESI) was operated in positive ion mode using an Applied Biosystems API 3200 LC/MS/MS as detector. Deuterated fentanyl (D5) and nor-fentanyl (D5) were used as internal standards (IS). The retention times for fentanyl and nor-fentanyl were 3.70min and 3.20min respectively. The lower limit of quantitation (LLOQ) was determined to be 0.030μg/L in plasma and 0.045 in saliva for fentanyl and nor-fentanyl. Acceptable linearity for fentanyl and nor-fentanyl in both plasma and saliva was demonstrated from 0.02 to 10μg/L (R2 0.9988-0.9994). Accuracy for fentanyl and nor-fentanyl in both plasma and saliva samples was between 96% and 108%. Total imprecision expressed as the co-efficient of variation was between 1.0 and 15.5% for both analytes in both matrices. The validated method was applied successfully in 11 paired plasma and saliva samples obtained from patients with cancer pain receiving transdermal fentanyl (Duragesic®) at doses from 25μg to 100μg.
Keyword Adsorption
Fentanyl
HPLC-MS/MS
Plasma
Saliva
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2015 Collection
School of Medicine Publications
School of Pharmacy Publications
 
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