Bioanalytical LC-MS of therapeutic oligonucleotides

Bioanalysis

Volumn 3, Issue 5, 2011, Pages 541-564

  Van Dongen, William D ^a   Niessen, Wilfried M A ^b,c  

^a Proxy Laboratories   (Netherlands)

^b Hyphen MassSpec Consultancy   (Netherlands)

^c VU UNIVERSITY AMSTERDAM   (Netherlands)

Author keywords

[No Author keywords available]

Indexed keywords

OLIGONUCLEOTIDE; SMALL INTERFERING RNA;

BODY FLUID; ELECTROSPRAY; ENZYME LINKED IMMUNOSORBENT ASSAY; INTERMETHOD COMPARISON; LIQUID CHROMATOGRAPHY; LIQUID LIQUID EXTRACTION; MASS SPECTROMETRY; PH; POLYMERASE CHAIN REACTION; PRECIPITATION; PROTEIN BINDING; QUANTITATIVE ANALYSIS; REVIEW; SOLID PHASE EXTRACTION; TEMPERATURE; VISCOSITY;

ANALYTIC SAMPLE PREPARATION METHODS; ANIMALS; CHROMATOGRAPHY, LIQUID; ENZYME-LINKED IMMUNOSORBENT ASSAY; HUMANS; MASS SPECTROMETRY; OLIGONUCLEOTIDES; POLYMERASE CHAIN REACTION;

EID: 79953075257     PISSN: 17576180     EISSN: 17576199     Source Type: Journal    
DOI: 10.4155/bio.11.8     Document Type: Review

References (100)

1. Wilkinson A. Oligonucleotide therapeutics: The next big thing. Scrip Exec. Brief. 1(4), 1-12 (2008).
2. Tafech A, Bassett T, Sparanese D, Lee CH. Destroying RNA as a therapeutic approach. Curr. Med. Chem. 13, 863-881 (2006).
3. Zhou D, He QS, Wang C, Zhang J, Wong-Staal F. RNA interference and potential applications. Curr. Top. Med. Chem. 6, 901-911 (2006). (Pubitemid 43796970)
4. Pushparaj PN, Melendez AJ. Short interfering RNA (siRNA) as a novel therapeutic. Clin. Exp. Pharmacol. Physiol. 33, 504-510 (2006).
5. Zhang HY, Du Q, Wahlestedt C, Liang Z. RNA interference with chemically modified siRNA. Curr. Top. Med. Chem. 6(9), 893-900 (2006). (Pubitemid 43796969)
6. Carthew RW, Sontheimer EJ. Origins and mechanisms of miRNAs and siRNAs. Cell 136(4), 642-655 (2009). Current review article on the biology of short interfering RNA (siRNA) and microRNA.
7. Castanotto D, Rossi JJ. The promises and pitfalls of RNA-interference- based therapeutics. Nature 457(7228), 426-433 (2009). Comprehensive review on the current challenges faced with siRNA therapeutics.
8. Hannon GJ, Rossi JJ. Unlocking the potential of the human genome with RNA interference. Nature 431(7006), 371-378 (2004). (Pubitemid 39265678)
9. Halder J, Kamat AA, Landen CN Jr et al. Focal adhesion kinase targeting using in vivo short interfering RNA delivery in neutral liposomes for ovarian carcinoma therapy. Clin. Cancer Res. 12(16), 4916-4924 (2006). (Pubitemid 44338579)
10. Takeshita F, Minakuchi Y, Nagahara S et al. Efficient delivery of small interfering RNA to bone-metastatic tumors by using atelocollagen in vivo. Proc. Natl Acad. Sci. USA 102(34), 12177-12182 (2005). (Pubitemid 41291148)
11. Frank-Kamenetsky M, Grefhorst A, Anderson NN et al. Therapeutic RNAi targeting PCSK9 acutely owers plasma cholesterol in rodents and LDL cholesterol in nonhuman primates. Proc. Natl Acad. Sci. USA 105(33), 11915-11920 (2008).
12. Sato Y, Murase K, Kato J et al. Resolution of liver cirrhosis using vitamin A-coupled liposomes to deliver siRNA against a collagen-specific chaperone. Nat. Biotechnol. 26(4), 431-442 (2008). (Pubitemid 351501817)
13. Bitko V, Musiyenko A, Shulyayeva O, Barik S. Inhibition of respiratory viruses by nasally administered siRNA. Nat. Med. 11(1), 50-55 (2005). (Pubitemid 40215837)
14. Song E, Lee SK, Wang J et al. RNA interference targeting Fas protects mice from fulminant hepatitis Nat. Med. 9(3), 347-351 (2003). (Pubitemid 36362792)
15. Niu X-Y, Peng ZL, Duan WQ, Wang H, Wang P. Inhibition of HPV 16 E6 oncogene expression by RNA interference in vitro and in vivo. Int. J. Gynecol. Cancer 16(2), 743-751 (2006).
16. Tamm I, Dorken B, Hartmann G. Antisense therapy in oncology: New hope for an old idea? Lancet 358, 489-497 (2001). (Pubitemid 32769863)
17. Tremblay GA, Oldfield PR. Bioanalysis of siRNA and oligonucleotide therapeutics in biological fluids and tissues. Bioanalysis 1(3), 595-609 (2009).
18. Yu RZ, Geary RS, Levin AA. Application of novel quantitative bioanalytical methods for pharmacokinetic and pharmacokinetic/pharmacodynamic assessments of antisense oligonucleotides. Curr. Opin. Drug Discov. Dev. 7(1), 195-203 (2004). (Pubitemid 44111951)
19. Yu RZ, Geary RS, Monteith DK et al. Tissue disposition of 20-O-(2-methoxy) ethyl modified antisense oligonucleotides in monkeys. J. Pharm. Sci. 93(2), 48-59 (2004). (Pubitemid 38081813)
20. Marcucci G, Stock W, Dai G et al. Phase I study of oblimersen sodium, an antisense to Bcl-2, in untreated older patients with acute myeloid leukemia: Pharmacokinetics, pharmacodynamics, and clinical activity. J. Clin. Oncol. 23(15), 3404-3411 (2005).
21. Arora V, Knapp DC, Reddy MT, Weller DD, Iverson PL. Bioavailability and efficacy of antisense morpholino oligomers targeted to c-myc and cytochrome P-450 3A2 following oral administration in rats. J. Pharm. Sci. 91(4), 1009-1018 (2002). (Pubitemid 34640926)
22. Deverre JR, Boutet V, Boquet D, Ezan E, Grassi J, Grognet JM. A competitive enzyme hybridization assay for plasma determination of phosphodiester and phosphorothioate antisense oligonucleotides. Nucl. Acids Res. 25, 3584-3589 (1997). (Pubitemid 27390175)
23. Cheng A, Li M, Liang Y et al. Stem-loop RT-PCR quantitation of siRNAs in vitro and in vivo. Nucleotides 19(2), 203-208 (2009).
24. Mulvana DE. Critical topics in ensuring data quality in bioanalytical LC-MS development. Bioanalysis 2(6), 1051-1072 (2010).
25. Fountain KJ, Gilar M, Gebler JC. Analysis of native and chemically modified oligonucleotides by tandem ion-pair reversed-phase high-performance liquid chromatography-electrospray ionization mass spectrometry. Rapid Commun. Mass Spectrom. 17, 646-653 (2003). (Pubitemid 36373163)
26. Gilar M. Analysis and purification of synthetic oligonucleotides by reversed-phase high-performance liquid chromatography with photodiode array and mass spectrometry detection. Anal. Biochem. 298, 196-206 (2001). (Pubitemid 33105234)
27. Wang G, Cole RB. Solution, gas phase, and instrumental parameter influences on charge state distributions in electrospray ionization mass spectrometry. In:Electrospray Ionization Mass Spectrometry - Fundamentals, Instrumentation and Applications. Cole RB (Ed.). John Wiley and Sons, NY, USA (1997).
28. Johnson JL, Guo W, Zang et al. Quantification of Raf antisense oligonucleotide (rafAON) in biological matrices by LC-MS/MS to support pharmacokinetics of a liposome-entrapped rafAON formulation. Biomed. Chromatogr. 19(4), 272-278 (2005). (Pubitemid 40872655)
29. Deforce DL, van de Eeckhout EG. Analysis of oligonucleotides by ESI-MS. Adv. Chromatogr. 40, 539-566 (2000). (Pubitemid 32120432)
30. Nordhof E, Kirpekar F, Roepstorf P. Mass spectrometry of nucleic acids. Mass Spectrom. Rev. 15, 67-138 (1996). (Pubitemid 126634227)
31. Bleicher K, Bayer E. Various factors influencing the signal intensity of oligonucleotides in electrospray mass spectrometry. Biol. Mass Spectrom. 23, 320-322 (1994). (Pubitemid 24161710)
32. Huang G, Krugh TR. Large-scale purification of synthetic oligonucleotides and carcinogen-modified oligodeoxynucleotides on a reverse-phase polystyrene (PRP-1). Column Anal. Biochem. 190, 21-25 (1990). (Pubitemid 20350124)
33. Huber CG, Krajete A. Analysis of nucleic acids by capillary ion-pair reversed-phase HPLC coupled to negative-ion electrospray ionization mass spectrometry. Anal. Chem. 71, 3730-3739 (1999).
34. Apffel A, Chakel JA, Fischer S, Lichtenwalter K, Hancock WS. Analysis of oligonucleotides by HPLC-electrospray ionization mass spectrometry. Anal. Chem. 69, 1320-1325 (1997).
35. Xu K, Williams EA, Wong S, Miller KJ, Geary RS, Yu RZ. Quantitation of antisense oligonucleotides in mouse plasma by LC-MS/MS. Proceedings of the 51st ASMS Conference on Mass Spectrometry and Allied Topics. Montreal, Quebec, June 2003.
36. Oberacher H, Oefner PJ, Parson W, Huber CG. On-line liquid chromatography-mass spectrometry: A useful tool for the detection of DNA sequence variation. Angew. Chem. Int. Ed. Engl. 40, 3828-3830 (2001). (Pubitemid 33009570)
37. Oberacher H, Parson W, Muhlmann R, Huber CG. Analysis of polymerase chain reaction products by on-line liquid chromatography-mass spectrometry for genotyping of polymorphic short tandem repeat loci. Anal. Chem. 73, 5109-5115 (2001). (Pubitemid 33032225)
38. Apffel A, Chakel JA, Fischer S, Lichtenwalter K, Hancock WS. New procedure for the use of high-performance liquid chromatography-electrospray ionization mass spectrometry for the analysis of nucleotides and oligonucleotides. J. Chromatogr. A 777(1), 3-21 (1997). n First publication describing the application of the 1,1,1,3,3,3-hexafluoro-2-propanol- triethylammonium ion-pair system for oligonucleotide therapeutic (OGNT) LC-MS analysis. (Pubitemid 27353323)
39. Lin ZJ, Li W, Dai G. Application of LC-MS for quantitative analysis and metabolite identification of therapeutic oligonucleotides. J. Pharm. Biomed. Anal. 44, 330-341 (2007). Previous review on bioanalytical LC-MS of OGNTs. (Pubitemid 46887636)
40. McCarthy SM, Martin Gilar M, Gebler J. Reversed-phase ion-pair liquid chromatography analysis and purification of small interfering RNA. Anal. Biochem. 390(2), 181-188 (2009).
41. McCarthy SM, Ivleva V, Gilar M, Yu Y-X, Gebler JC. Ion-pairing reversed for LC-MS and MS/MS characterization of RNAi. Poster presented on 5th Symposium on the Practical Applications of Mass Spectrometry in the Biotechnology and Pharmaceutical Industries. The Meritage Resort, Napa, CA, USA, 9-11 September 2008.
42. He L, Chen Y-S, Lam Z et al. Antisense oligonucleotides (ASO) metabolism study by LC-MS/MS in Support of ASO drug discovery and development. Proceedings of the 52nd ASMS Conference on Mass Spectrometry and Allied Topics. Nashville, TN, USA, 23-27 May 2004.
43. Zang J, Johnson JL, Guo W et al. Quantification of a raf antisense oligonucleotide (rafAON) by LC-MS/MS in biological matrices containing liposome-entrapped rafAON (LErafAON-ETU). Proceedings of the 52nd ASMS Conference on Mass Spectrometry and Allied Topics. Nashvile, TN, USA, 23-27 May 2004.
44. Dai G, Wei X, Liu Z, Liu S, Marcucci G, Chan KK. Characterization and quantification of Bcl-2 antisense G3139 and metabolites in plasma and urine by ion-pair reversed phase HPLC coupled with electrospray ion-trap mass spectrometry. J. Chromatogr. B Analyt. Technol. Biomed. Life Sci. 825, 201-213 (2005). (Pubitemid 41423604)
45. Zhang G, Lin J, Srinivasan K, Kavetskaia O, Duncan NJ. Strategies for bioanalysis of an oligonucleotide class macromolecule from rat plasma using liquid chromatography-tandem mass spectrometry. Anal. Chem. 79(9), 3416-3424 (2007). (Pubitemid 46717172)
46. Deng P, Chen X, Zhang G, Zhong D. Bioanalysis of an oligonucleotide and its metabolites by liquid chromatography-tandem mass spectrometry. J. Pharm. Biomed. Anal. 52(4), 571-579 (2010). n State-of-the art example of quantitative LC-MS of an OGNT and its metabolites in plasma.
47. Wong P, Bruenner B, James C. Bioanalytical method development for the determination of antisense oligonucleotides in mouse plasma by reverse phase ion-pair liquid chromatography-negative ion electrospray tandem mass spectrometry. Proceedings of: The 57st ASMS Conference on Mass Spectrometry and Allied Topics. Philidelphia, PA, USA, 31 May-4 June 2009.
48. Wheller R. The extraction and analysis of siRNA from rat plasma using mixed mode SPE and HPLC-MS/MS. Proceedings of the 58st ASMS Conference on Mass Spectrometry and Allied Topics. Salt Lake City, UT, USA, May 2010.
49. Oberacher H, Premstaller A, Huber CG. Characterization of some physical and chromatographic properties of monolithic poly(styrene-co-divinylbenzene) columns. J. Chromatogr. A 1030, 201-208 (2004). (Pubitemid 38221330)
50. Premstaller A, Oberacher H, Huber CG. High-performance liquid chromatography-electrospray ionization mass spectrometry of single- and double-stranded nucleic acids using monolithic capillary columns. Anal. Chem. 72, 4386-4393 (2000).
51. Hölzl G, Oberacher H, Pitsch S, Stutz A, Huber CG. Analysis of synthetic and biological RNA by liquid chromatography-mass spectrometry using monolithic columns. Anal. Chem. 77, 673-680 (2005). (Pubitemid 40116852)
52. Light-Wahl K, Springer D, Winger B et al. Observation of a small oligonucleotide duplex by electrospray ionization mass spectrometry. J. Am. Chem. Soc. 115(2), 803-804 (1993).
53. Bayer E, Bauer T, Schmeer K, Bleicher K, Maier M, Gaus M. Analysis of double-stranded oligonucleotides by electrospray mass spectrometry. Anal. Chem. 66(22), 3858-3863 (1994).
54. Gale DC, Smith RD. Characterization of noncovalent complexes formed between minor groove binding molecules and duplex DNA by electrospray ionization-mass spectrometry. J. Am. Soc. Mass Spectrom. 6, 1154-1164 (1995).
55. Loo JA. Studying noncovalent protein complexes by electrospray ionization mass spectrometry. Mass Spectrom. Rev. 16(1), 1-23 (1997). (Pubitemid 127583217)
56. Schnier PD, Klassen JS, Strittmatter EF, Williams ER. Activation energies for dissociation of double strand oligonucleotide anions: Evidence for watson-crick base pairing in vacuo. J. Am. Chem. Soc. 120(37), 9605-9613 (1998). (Pubitemid 28452652)
57. Gabelica V, De Pauw E. Comparison between solution-phase stability and gas-phase kinetic stability of oligodeoxynucleotide duplexes. J. Mass Spectrom. 36(4), 397-402 (2001). (Pubitemid 32409884)
58. Rodrigues Hoyne P, Benson LM, Veenstra TD, Maher LJ, Naylor S. RNA-RNA noncovalent interactions investigated by microspray ionization mass spectrometry. Rapid Commun. Mass Spectrom. 15 1539-1547 (2001). (Pubitemid 32834975)
59. Beck JL, Colgrave ML, Ralph SF, Sheil MM, Electrospray ionization mass spectrometry of oligonucleotide complexes with drugs, metals, and proteins. Mass Spectrom. Rev. 20, 61-87 (2001). (Pubitemid 32695921)
60. Mangrum JB, Flora JW, Muddiman DC. Solution composition and thermal denaturation for the production of single-stranded PCR amplicons: Piperidine-induced destabilization of the DNA Duplex? J. Am. Soc. Mass Spectrom. 13(3), 232-240 (2002). (Pubitemid 34552603)
61. Beverly M, Hartsough K, Machemer L. Liquid chromatography-electrospray mass spectrometric analysis of metabolites from an inhibitory RNA duplex. Rapid Commun. Mass Spectrom. 835, 1675-1682 (2005). (Pubitemid 40831949)
62. Beverly M, Hartsough K, Machemer L, Pavco P, Lockridge J. Liquid chromatography-electrospray ionization mass spectrometry analysis of the ocular metabolites from a short interfering RNA duplex. J. Chromatogr. B Analyt. Technol. Biomed. Life Sci. 835, 62-70 (2006). Currently, the only application of (semi-)quantitative determintation of intact siRNA and metabolites in biological fluids using LC-MS.
63. Gilar M, Fountain KJ, Budman Y et al. Ion-pair reversed-phase high-performance liquid chromatography analysis of oligonucleotides: Retention prediction J. Chromatogr. A 958, 167-182 (2002). (Pubitemid 34556947)
64. Huber CG, Krajete A. Sheath liquid effects in capillary high-performance liquid chromatography-electrospray mass spectrometry of oligonucleotides. J. Chromatogr. A 870, 413-424 (2000). (Pubitemid 30077444)
65. Harsch A, Sayer JM, Jerina DM, Vouros P. HPLC-MS/MS identification of positionally isomeric benzo(c)phenanthrenediol epoxide adducts in duplex DNA. Chem. Res. Toxicol. 13, 1342-1348 (2000). (Pubitemid 32106679)
66. Witters E, Van Dongen W, Esmans EL, Van Onckelen HA. Ion-pair liquid chromatography-electrospray mass spectrometry for the analysis of cyclic nucleotides. J. Chromatogr. B Biomed. Sci. Appl. 694, 55-63 (1997). (Pubitemid 27273991)
67. Huber CG, Oberacher H. Analysis of nucleic acids by on-line liquid chromatography-mass spectrometry Mass Spectrom. Rev. 20(5), 310-343 (2001). (Pubitemid 34514981)
68. Ahmad A, Khan S, Duan L et al. Quantification of a 15-mer antisense oligonucleotide in human plasma by liquid chromatography-tandem mass spectrometry. Proceedings of the 50th ASMS Conference on Mass Spectrometry and Allied Topics. Orlando, FL, USA, 2-6 June 2002.
69. Ahmad A, Khan S, Ahmad I. Mass spectrometry and enzyme-linked immunosorbent assay methods for the quantitation of liposomal antisense oligonucleotide (LE-rafAON) in human plasma. Meth. Enzymol. 387, 230-241 (2004).
70. Zou Y, Tiller P, Chen I-W, Beverly M, Hochman J. Metabolite identification of small interfering RNA duplex by high-resolution accurate mass spectrometry. Rapid Commun. Mass Spectrom. 22, 1871-1881 (2008). (Pubitemid 351947753)
71. Muddiman DC, Cheng X, Udseth HR, Smith RD. Charge-state reduction with improved signal intensity of oligonucleotides in electrospray ionization mass spectrometry. J. Am. Soc. Mass Spectrom. 7, 697-706 (1996). (Pubitemid 26286923)
72. Cheng X, Gale D, Udseth HR, Smith RD. Charge state reduction of oligonucleotide negative ions from electrospray ionization. Anal. Chem. 67, 586-593 (1995).
73. Greig M, Griffey RH. Utility of organic bases for improved electrospray mass spectrometry of oligonucleotides. Rapid Commun. Mass Spectrom. 9, 97-105 (1995).
74. Deguchi K, Ishikawa M, Yokokura T et al. Enhanced mass detection of oligonucleotides using reverse-phase high-performance liquid chromatography-electrospray ionization ion-trap mass spectrometry. Rapid Commun. Mass Spectrom. 16(22), 2133-2141 (2002). (Pubitemid 35340080)
75. Coleman RS. Analysis of post-synthetically modified oligodeoxynucleotides by electrospray ionization mass spectrometry. Bioorg. Med. Chem. Lett. 4, 1869-1874 (1994).
76. Oberacher H, Walcher W, Huber CG. Effect of instrument tuning on the detectabilityof biopolymers in electrospray ionization mass spectrometry. J. Mass Spectrom. 38, 108-116 (2003). (Pubitemid 36157763)
77. Griffey RH, Sasmor H, Greig MJ. Oligonucleotide charge states in negative ionization electrospray-mass spectrometry are a function of solution ammonium ion concentration. J. Am. Soc. Mass Spectrom. 8(2), 155-160 (1997). (Pubitemid 27044822)
78. Gilar M, Belenky A, Wang BH. High-throughput biopolymer desalting by solid-phase extraction prior to mass spectrometric analysis. J. Chromatogr. A 921, 3-13 (2001). (Pubitemid 32530721)
79. Castleberry CM, Rodicio LP, Limbach PA. Electrospray ionization mass spectrometry of oligonucleotides. Curr. Protoc. Nucleic Acid Chem. 10(10.2), (2008).
80. Hail ME, Elliott B, Anderson K. High-throughput analysis of oligonucleotides using automated electrospray ionization mass spectrometry. Am. Biotechnol. Lab. 22, 12-14 (2004). (Pubitemid 41819657)
81. Little D, Thannhauser TW, McLafferty FW. Verification of 50- to 100-mer DNA and RNA sequences with high-resolution mass spectrometry. Proc. Natl Acad. Sci. USA 92(6), 2318-2322 (1995).
82. Little D, Aaserud DJ, McLafferty FW. Sequence information from 42-108-mer DNAs (complete for a 50-mer) by tandem mass spectrometry. J. Am. Chem. Soc. 118(39), 9352-9359 (1996). (Pubitemid 26355129)
83. Gentil E, Banoub J. Characterization and differentiation of isomeric self-complementary DNA oligomers by electrospray tandem mass spectrometry. J. Mass Spectrom. 31(1), 83-94 (1996).
84. Sannes-Lowery KA, Hofstadler SA.Sequence confirmation of modified oligonucleotides using IRMPD in the external ion reservoir of an electrospray ionization fourier transform ion cyclotron, mass spectrometer. J. Am. Chem. Soc. 14(8), 825-833 (2003). (Pubitemid 36904255)
85. McLuckey SA, Van Berkel GJ, Glish GL. MS-MS of small multiply charged oligonucleotides. J. Am. Soc. Mass Spectrom. 3, 60-70 (1992).
86. Murray KK. DNA sequencing by MS. J. Mass Spectrom. 31, 1203-1215 (1996).
87. Ni J, Pomerantz SC, Rozenski J, Zhang Y, McCloskey JA. Interpretation of oligonucleotide mass spectra for determination of sequence using ESI-MS/MS. Anal. Chem. 68, 1989-1999 (1996).
88. Matuszewski BK, Constanzer ML, Chavez-Eng CM. Strategies for the assessment of matrix effect in quantitative bioanalytical methods based on LC-MS/MS. Anal. Chem. 75(13), 3019-3030 (2003). (Pubitemid 36830428)
89. Murphy AT, Brown-Augsburger P, Yu RZ, Geary RS, Thibodeaux S, Ackermann BL. Development of an ion-pair reversed-phase liquid chromatography-tandem mass spectrometry method for the determinationof an 18-mer phosphothioate oligonucleotide in mouse liver tissue. Eur. J. Mass Spectrom. 11(2), 209-215 (2005). (Pubitemid 41241585)
90. Li Y, Tan B, Fitzgerald TJ et al. Quantitation analysis of phosphorothioate oligodeoxynucleotides (ISIS 1082) by LC-MS/MS. Proceedings of the 49th ASMS Conference on Mass Spectrometry and Allied Topics. Chicago, IL, USA, 27-31 May 2001.
91. German MW, Pon RT, van de Sande JH. A general method for the purification of synthetic oligodeoxyribonucleotides containing strong secondary structure by reversed-phase high-performance liquid chromatography on PRP-1 resin. Anal. Biochem. 165, 399-405 (1987).
92. Shishkina IG, Johnson F. A new method for the postsynthetic generation of abasic sites in oligomeric DNA. Chem. Res. Toxicol. 13, 907-912 (2000).
93. Calvitt CJ, Levin DS, Shepperd BT, Gruenloh CJ. Chemistry at the 2' position of constituent nucleotides controls degradation pathways of highly modified oligonucleotide molecules. Oligonucleotides 20(5), 239-251 (2010).
94. Wei X, Dai G, Liu Z et al. Metabolism of GTI-2040, a phosphorothioate oligonucleotide antisense, using ion-pair reversed phase high performance liquid chromatography (HPLC) coupled with electrospray ion-trap mass spectrometry. AAPS J. 8, E743-E755 (2006).
95. 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).
96. Beverly MB. Applications of mass spectrometry to the study of siRNA. Mass Spec. Rev. DOI: 10.1002/mas.20260 (2010). (Epub ahead of print). Comprehensive review on the current status of mass spectrometric analysis of intact siRNA.
97. Gaus HJ, Owens SR, Winniman M, Cooper S, Cummins LL. On-line HPLC-electrospray mass spectrometry of phosphorothioate oligonucleotide metabolites. Anal. Chem. 69, 313-319 (1997).
98. Noll BO, McCluskie MJ, Sniatala T et al. Biodistribution and metabolism of immunostimulatory oligodeoxynucleotide CPG 7909 in mouse and rat tissues following subcutaneous administration. Biochem. Pharmacol. 69, 981-991 (2005). (Pubitemid 40312715)
99. Efler SM, Zhang L, Noll BO, Uhlmann E, Davis HL. Quantitation of oligodeoxynucleotides in human plasma with a novel hybridization assay offers greatly enhanced sensitivity over capillary electrophoresis. Oligonucleotides 15(2), 119-131 (2005). (Pubitemid 40967417)
100. Stratford S, Stec S, Jadhav V, Seitzer J, Abrams M, Beverly M. Examination of real-time polymerase chain reaction methods for the detection and quantification of modified siRNA. Anal. Biochem. 379(1), 96-104 (2008).