We use cookies to improve your experience. By continuing to browse this site, you accept our cookie policy.×
Published Online:https://doi.org/10.4155/bio.14.290

In bioanalysis of small molecules, the analyte concentration in the measured samples should reflect the concentration during sample collection. Precautions may be needed to prevent over- or under-estimation of the obtained result. This might require the addition of stabilizers to prevent degradation or nonspecific binding. For unstable drugs, it is essential to know how analytes can be stabilized before the start of the clinical study. Although the stabilization methods are well documented, the impact of the stabilization on the clinical workflow is not properly addressed. Already during method development, the clinical implications in terms of personnel safety, ease of use, training possibilities and staff capacity should be taken into account, and validation of the bioanalytical method should reflect collection procedures.

Papers of special note have been highlighted as: • of interest; •• of considerable interest

References

  • 1 Van de Merbel N, de Vries R. Aging of biological matrices and its effect on bioanalytical method performance. Bioanalysis 5(19), 2393–2407 (2013).
  • 2 Briscoe CJ, Hage DS. Factors affecting the stability of drugs and drug metabolites in biological matrices. Bioanalysis 1(1), 205–220 (2009).•• Excellent review article on the stability issues in bioanalysis.
  • 3 Ohnmacht CM. LC–MS bioanalysis of photosensitive and oxidatively labile compound. In: Handbook Of LC–MS Bioanalysis, Best Practices Experimental Protocols And Regulations. John Wiley and Sons, Inc, NY, USA, 491–504 (2013).
  • 4 Peters FT. Stability of analytes in biosamples- an important issue in clinical and forensic toxicology? Anal. Bioanal. Chem. 388(7), 1505–1519 (2007).
  • 5 Ji AJ, Jiang Z, Livson Y, Davis JA, Chu JX, Weng N. Challenges in urine bioanalytical assays: overcoming non specific binding. Bioanalysis 2(9), 1573–1586 (2010).•• Good overview of strategies for urine sampling.
  • 6 Li W, Zhang J, Tse FL. Strategies in quantitative LC–MS/MS analysis of unstable small molecules in bioanalytical matrixes. Biomed. Chromatogr. 25(1–2), 258–277 (2011).
  • 7 Chen J, Hsieh Y. Stabilizing drug molecules in biological samples. Ther. Drug Monit. 27(5), 617–624 (2005).
  • 8 Van der Merbel N, Savoie N, Yadav M et al. Stability: recommendation for best practices and harmonization from the Global Bioanalysis Consortium Harmonization team. AAPS J. 16(3), 392–399 (2014).
  • 9 Heinig K. What are the challenges of stability investigations and sample stabilization in regulated bioanalysis. Bioanalysis 5(15), 1811–1814 (2013).• Good editorial on stability investigations and stability aspects.
  • 10 Sennbro CJ, Knutsson M, van Amsterdam P, Timmerman P. Anticoagulant counter ion impact on bioanalytical LC–MS/MS assays: results from discussions and experiments within the European Bioanalytical Forum. Bioanalysis 3(21), 2393–2399 (2011).
  • 11 Japanese Ministry of Health, Welfare and Labour. Guideline on Bioanalytical Method Validation in Pharmaceutical Development (2013).
  • 12 Brazilian Agência de Nacional de Vigilância Sanitária. Resolution- RDC Nº 27, Requirements for the validation of bioanalytical methods (2012). http://bcn2012.europeanbioanalysisforum.eu/slides/day%203/7%20updates%20from%20the%20globe/3_tavares.pdf.
  • 13 US Department of Health and Human Services, Food and Drug Administration, Center for Drug Evaluation and Research, Center for Veterinary Medicine. Guidance for Industry: Bioanalytical Method Validation. (2001). www.fda.gov/downloads/Drugs/Guidances/ucm070107.pdf.
  • 14 US Department of Health and Human Services, Food and Drug Administration, Center for Drug Evaluation and Research, Center for Veterinary Medicine. Guidance for Industry: Bioanalytical Method Validation. Draft Guidance. September 2013.
  • 15 European Medicines Agency, Committee for Medicinal Products for Human Use. Guideline on bioanalytical method validation. (2011). www.ema.europa.eu/docs/en_GB/document_library/Scientific_guideline/2011/08/WC500109686.pdf.
  • 16 Boterman M, DOIG m, Breda M et al. Recommendations on the interpretation of the new European medicines agency guideline on bioanalytical method validation by global CRO council for bioanalysis (GCC). Bioanalysis 4(6), 651–660 (2012).
  • 17 Lowes S, Jersey J, Shoup R et al. Recommendations on: internal standard criteria, stability, incurred sample reanalysis and recent 483s by the global CRO council for bioanalysis. Bioanalysis 3(12), 1223–1332 (2011).
  • 18 van Amsterdam P, Companjen A, Brudny-Kloeppel M, Golob M, Luedtke S, Timmerman P. The European Bioanalysis forum community's evaluation, interpretation and implementation of the European Medicines Agency guideline on Bioanalytical Method validation. Bioanalysis 5(6), 645–659 (2013).
  • 19 Freisleben A, Brudny-Klöppel M, Mulder H, de Vries R, de Zwart M, Timmerman P. Blood stability testing: European Bioanalysis Forum view on current challenges for regulated bioanalysis. Bioanalysis 3(12), 1333–1336 (2011).
  • 20 Viswanathan CT, Basal S, Booth B et al. Workshop/Conference Report-Quantitave bioanakytical methods validation and implementation: best practices for chromatographic and ligand binding assay. AAPS J 9, E30–E42 (2007).
  • 21 Timmerman P. Tiered approach revisited: introducing stage-approach or assay-appropriate scientific validation. Bioanalysis 6(5), 599–604 (2014).• Good commentary on the level of scientific validation needed for bioanalytical studies.
  • 22 Timmerman P, White S, Knutsson M et al. Feedback from the EBF workshop: taking tiered approach to the next level. Bioanalysis 6(19), 2593–2598 (2014).
  • 23 Hilhorst MJ, Hendriks G, Van Hout MW, Sillen H, van de Merbel NC. HPLC–MS/MS method for the determination of cytarabine in human plasma. Bioanalysis 3(14), 1603–1611 (2011).
  • 24 Fung EN, Zheng N, Arnold ME et al. Effective screening approach to select esterase inhibitors used for stabilizing ester containing prodrugs analyzed by LC–MS/MS. Bioanalysis 2(4), 733–743 (2010).• General article on the use of enzyme inhibitors.
  • 25 Du L, Musson DG. Stability studies of vorinostat and its two metabolites in human plasma serum and urine. J. Pharm. Biomed. Anal. 42(5), 556–564 (2006).
  • 26 Gruenke LD, Craig JC, Klein FD et al. Determination of chlorpromazine and its major metabolites by gas chromatography/mass spectrometry: application to biological fluids. Biomed. Mass Spectrom. 12(12), 707–713 (1985).
  • 27 Suchocka Z, Swatowska J, Pachecka J, Suchocki P. Determination of paraoxonase 3 activity in human blood serum. J. Pharm. Biomed. Anal. 42(1), 113–119 (2006).
  • 28 Bieri JG, Evarts RP, Thorpe S. Factors affecting the exchange of tocopherol between red blood cells and plasma. Am. J. Clin. Nutr. 30, 686–690 (1977).
  • 29 Lentjes EG, Romijn FH. Temperature dependent cortisol distribution among blood compartments in man. J. Clin. Endocrinol. Metab. 84, 682–687 (1999).
  • 30 Atkinson K, Britton K, Biggs J. Distribution and concentration of cyclosporine in human blood. J. Clin. Pathol. 37, 1167–1171 (1984).
  • 31 Fišar Z, Fuksová K, Sikora J et al. Distribution of antidepressants between plasma and red blood cells. Neuroendocrinol. Lert. 27, 307–313 (2006).
  • 32 Arrhenius S. Ueber die Reaktionsgeschwindigkeit bei der Inversion von Rohrzucker durch Säuren. Z. Phys. Chem. 4, 226–248 (1889).
  • 33 Arrhenius S. “Zur Theorie der chemischen Reaktionsgeschwindigkeit,” in Bihang, 24, no.2 (1898). Z. phys. Chem. 28, 317–335 (1899).
  • 34 Aranov PA, Hall LM, Dettmer K, Stephensen CB, Hammock BD. Metabolic profiling of major vitamin D metabolites using Diels Alder derivatisation and ultra-performance-liquid – chromatogrpahy tandem mass spectrometry. Anal. Bioanal. Chem. 391, 1917–1930 (2008).
  • 35 Anderson A, Ehrsson H. Stability of cisplatin and its monohydrated complex in blood, plasma and ultrafiltrate. J. Pharm. Biomed. Anal. 13, 639–644 (1995).
  • 36 Fura A, Harper TW, Zhang H, Fung L, Shyu WC. Shift in pH of biological fluids during storage and processing: effect on bioanalysis. J. Pharm. Biomed. Anal. 32, 513–522 (2003).
  • 37 Van de Merbel N, de Vries R. Age of biological matrices and its effect on bioanalytical method performance. Bioanalysis 5(19), 2393–2407 (2013).
  • 38 T. Ebner T, Heinzel G, Prox A, Beschke, Wachsmuth H. Disposition and chemical stability of telmisartan 1-o-acylglucuronide. Drug Metab. Dispos. 27(10), 1143–1149 (1999).
  • 39 Dell D. Labile metabolites. Chromatographia 59, S139–S148 (2004).
  • 40 Van de Merbel, Hendriks G, Imbos R, Tuunainen J, Rouru J, Nikkanen H. Quantitative determination of free and total dopamine in human plasma by LC–MS/MS: the importance of sample preparation. Bioanalysis 3(17), 1949–1961 (2011).
  • 41 Van de Merbel NC, Bronsema KJ, van Hout MW, Nilsson R, Sillen H. A validated liquid chromatograqphy-tandem mass spectrometry method for the quantitative determination of 4β-hydroxycholesterole in human plasma. J. Pharm. Biomed. Anal. 55(5), 1089–1095 (2011).
  • 42 Wang G, Hsieh Y, Lau Y et al. Semi-automated determination of plasma stability of drug discovery compounds using liquid chromatography-tandem mass spectrometry. J. Chromatogr. B. Analyt. Technol. Biomed. Life Sci. 780(2), 451–457 (2002).
  • 43 Lindegardh N, Davies GR, Hien TT et al. Importance of collection tube during clinical studies of oseltamivir. Antimicrob. Agents Chemother. 51(5), 1835–1836 (2007).
  • 44 Pham-huy C, Villain-Pautet G, Hua H et al. Seperation of oxazepam. Lorazepam and temazepam enantiomers by HPLC on a derivatized cyclodextrin-bonded phase: application to the determination of oxazepam in plasma. J. Biochem. Biophys. Meth 54, 287–299 (2002).
  • 45 Zhao Y, Sukbunthernq J, Antonian L. Simultanious determination of Z-Su5416 and its interconvertible geometric E-isomer in rat plasma by LC/MS/MS. J. Pharm. Biomed. Anal. 35(3), 513–522 (2004).
  • 46 Yan KX, Song H, Lo MW. Determination of MK-0767 enantiomers in human plasma by normal phase LC–MS/MS. J. Chromatogr. B 813, 95–102 (2004).
  • 47 Wang CJ, pao LH, Hsiong CH, Wu CY, Whang-Peng JJ, Hu OYP. Novel inhibition of cis/trans retinoic acid interconversion in biological fluids – an accurate method for the determination of trans and 13-cis retinoic acid in biological fluids. J. Chromatogr. B. 796(2), 283–291 (2003).
  • 48 Jemal M, Khan S, Teitz DS, McCafferty JA, Hawthorne DJ. LC/MS/MS determination ofomapatrilat, a sulfhydryl-containing vasopeptidase inhibitor, and its sulfhydryl- and thioether-containing metabolites in human plasma. Anal. Chem, 73, 5450–5456 (2001).
  • 49 Abu-Shandi KH, Redel E. Quantification and stability evaluation of the highly specific angiotensin-converting enzyme (ACE) inhibitor Captopril in human plasma using a gas chromatography method woth N,N,N’,N’-tetramethyl-2-butenediamide derivatisation agent. Jordan J. Chem. 4, 189–194 (2009).
  • 50 Ji AJ. LC–MS bioanalysis of drugs in urine. In: Handbook of LC–MS Bioanalysis, best practices experimental protocols and regulations. John Wiley and Sons, Inc, NY, USA, 307–316 (2013).
  • 51 Vainchtein LD, Rosing H, Mirejovsky D, Lenaz L, Schellens JHM, Beijnen JH. Stability experiments in human urine with E09 (apaziquone): a novel anticancer agent for the intravesical treatment of bladder cancer. J. Pharm. Biomed. Anal. 43(1), 285–292 (2007).