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LC Determination of Ritonavir, a HIV Protease Inhibitor, in Soft Gelatin Capsules

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Abstract

A rapid, simple and sensitive high-performance liquid chromatographic method (HPLC) has been developed to assay ritonavir in semisolid capsules. The HPLC analysis used a reversed-phase C8 (125 × 4.0 mm i.d., 5 μm particle size) analytical column and a mobile phase consisting of methanol and water (67:33, v/v), with UV detection at 210 nm. Specificity was evaluated using a photodiode array detector (PDA). The validation data showed that the assay is sensitive, specific and reproducible for determination of ritonavir in this dosage form. Calibration curves were linear from 100–300 μm L−1 (R2 ≥ 0.999). The accuracy of the method ranged from 98.8 to 102.0%. Mean inter- and intra-assay relative standard deviations (RSD) were less than 1.0%. The proposed method provided an accurate and precise analysis of ritonavir in soft capsules, requiring neither the use of a buffered mobile phase, nor the addition of amine modifiers.

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References

  • Sethi ML (2002) Antiviral Agents and Protease Inhibitors. In: Foye's Principles of Medicinal Chemistry, Williams DA, Lemke TL, Philadelphia

  • Tavares W (1996) Manual de Antibióticos e Quimioterápicos Antiinfecciosos, São Paulo

  • Raffanti S, Haas DW (2001) Antimicrobial Agents-Antiretroviral Agents. In: Goodman & Gilman's The Pharmacological Basis of Therapeutics, Hardman JG, Limbird LE (eds) Gilman AG, USA

  • Abbott Laboratories, Norvir® (ritonavir capsules) Soft Gelatin / (ritonavir oral solution), North Chicago, IL 60064, U.S.A., Ref.: 03-5409-R20, Revised: January, 2005: http://www.norvir.com/pdf/norpi2a.PDF

  • Chen X, Kempf DJ, Li L, Sham HL, Vasavanonda S, Wideburg NE, Saldivar A, Marsh KC, McDonald E, Norbeck DW (2003) Bioorg Med Chem Lett 13:3657–3660

    CAS  Google Scholar 

  • Korolkovas A (2004) Dicionário Terapêutico Guanabara, Rio de Janeiro

  • Murphy RL (2003) J Acquir Immune Defic Syndr 33:S33-S56.

    Google Scholar 

  • FDA, HIV/AIDS Timeline Chronology of Significant Events, September, 2004: http://www.fda.gov/oashi/aids/miles.html

  • O'Neil MJ, Smith A, Heckelman PE, Budavari S (eds) (2001) The Merck Index: An Encyclopedia of Chemicals, Drugs & Biologicals, Whitehouse Station, NJ

    Google Scholar 

  • Marsh KC, Eiden E, McDonald E (1997) J Chromatogr B Biomed Sci Appl 704:307–313

    Article  CAS  Google Scholar 

  • Hoetelmans RM, van Essenberg M, Profijt M, Meenhorst PL, Mulder JW, Beijnen JH (1998) J Chromatogr B Biomed Sci Appl 705:119–126

    Article  CAS  Google Scholar 

  • Frappier S, Breilh D, Diart E, Ba B, Ducint D, Pellegrin JL, Saux MC (1998) J Chromatogr B Biomed Sci Appl 714:384–389. DOI: 10.1016/s0378–4347(98)00220-5

    Google Scholar 

  • Marzolini C, Telenti A, Buclin T, Biollaz J, Decosterd LA (2000) J Chromatogr B Biomed Sci Appl 740:43–58. DOI: 10.1016/s0378-4347(99)00573-3

    Google Scholar 

  • Dailly E, Thomas L, Kergueris MF, Jolliet P, Bourin M (2001) J Chromatogr B Biomed Sci Appl 758:129–135. DOI: 10.1016/s0378-4347(01)00117-7

    Google Scholar 

  • Sarasa-Nacenta M, López-Púa Y, Mallolas J, Blanco JL, Gatell JM, Carné X (2001) J Chromatogr B Biomed Sci Appl 757:325–332. DOI: 10.1016/s0378-4347(01)00172-4

    Google Scholar 

  • Yamada H, Kotaki H, Nakamura T, Iwamoto A (2001) J Chromatogr B Biomed Sci Appl 755:85–89. DOI: 10.1016/s0378-4347(00)00617-4

    Google Scholar 

  • Leibenguth P, Le Guellec C, Besnier JM, Bastides F, Macé M, Gaudet ML, Autret-Leca E, Paintaud G (2001) Ther Drug Monit 23:679–688

    Article  CAS  Google Scholar 

  • Simon VA, Thiam MD, Lipford LC (2001) J Chromatogr A 913:447–453. DOI: 10.1016/s0021-9673(00)01092-x

    Google Scholar 

  • Villani P, Feroggio M, Gianelli L, Bártoli A, Montagna M, Maserati R, Regazzi MB (2001) Ther Drug Monit 23:380–388

    Article  CAS  Google Scholar 

  • Volosov A, Napoli KL, Soldin SJ (2001) Clin Biochem 34:285–290

    Article  CAS  Google Scholar 

  • Janoly A, Beyzac N, Favetta P, Gagneu MC, Bourhis Y, Coudray S, Oger I, Aulagner G (2002) J Chromatogr B Biomed Sci Appl 780:155–160

    CAS  Google Scholar 

  • Ray J, Pang E, Carey D (2002) J Chromatogr B Biomed Sci Appl 775:225–230

    CAS  Google Scholar 

  • Marzolini C, Béguin A, Telenti A, Schreyer A, Buclin T, Biollaz J, Decosterd LA (2002) J Chromatogr B Biomed Sci Appl 774:127–140. DOI: 10.1016/s1570-0232(02)00169-1

    Google Scholar 

  • Titier K, Lagrange F, Péhourcq F, Edno-Mcheik L, Moore N, Molimard M (2002) Therapie 57:169–174

    CAS  Google Scholar 

  • Tribut O, Arvieux C, Michelet C, Chapplain JM, Allain H, Bentue-Ferrer D (2002) Ther Drug Monit 24:554–562. DOI: 10.1097/01.FTD.0000017718.61918.93

    Google Scholar 

  • Poirier JM, Robidou P, Jaillon P (2002) Ther Drug Monit 24:302–309

    Article  CAS  Google Scholar 

  • Chi JD, Jayewardene AL, Stone JA, Motoya T, Aweeka FT (2002) J Pharm Biomed Anal 30:675–684

    Article  CAS  Google Scholar 

  • Turner ML, Reed-Walker K, King JR, Acosta EP (2003) J Chromatogr B Biomed Sci Appl 784:331–341

    CAS  Google Scholar 

  • Justesen US, Pedersen C, Klitgaard NA (2003) J Chromatogr B Biomed Sci Appl 783:491–500

    CAS  Google Scholar 

  • Faux J, Venisse N, Le Moal G, Dupuis A, Bouquet S (2003) Chromatographia 58:421–426. DOI: 10.1365/s10337-003-0076-90009-5893/03/10

    Google Scholar 

  • Droste JAH, Verweij-van Wissen CPWGM, D.M. Burger DM (2003) Ther Drug Monit 25:393–399

    Google Scholar 

  • Walson PD, Cox S, Utkin I, Gerber N, Crim L, Brady M, Koranyi K (2003) Ther Drug Monit 25: 588–592

    Google Scholar 

  • Frerichs VA, DiFrancesco R, Morse GD (2003) J Chromatogr B Biomed Sci Appl 787:393–403

    CAS  Google Scholar 

  • Rentsch KM (2003) J Chromatogr B Biomed Sci Appl 788:339–350

    CAS  Google Scholar 

  • The United States Pharmacopeia, 28th (2005), Rockville, MD

  • ICH (1994) Harmonised Tripartite Guideline, Text on Validation of Analytical Procedures, Q2A. In: International Conference on Harmonization of Technical Requirements for Registration of Pharmaceuticals for Human Use

  • ICH (1996) Harmonised Tripartite Guideline, Validation of Analytical Procedures: Methodology, Q2B. In: International Conference on Harmonization of Technical Requirements for Registration of Pharmaceuticals for Human Use

  • FDA (1994) Center for Drug Evaluation and Research. Reviewer Guidance: Validation of Chromatographic Methods, Rockville, MD

    Google Scholar 

  • Bakshi M, Singh S (2002) J Pharm Biomed Anal 28:1011–1040

    Article  CAS  Google Scholar 

  • Rowe RC, Sheskey PJ, Weller PJ (eds) (2000) Handbook of Pharmaceutical Excipients, Washington

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Authors and Affiliations

  1. Curso de Pós-Graduação em Ciências Farmacêuticas, Faculdade de Farmácia, UFRGS Av. Ipiranga, 2752, Porto Alegre, CEP 90610-000, RS, Brasil

    C.L. Dias, R.C. Rossi, E.M. Donato, A.M. Bergold & P.E. Fröehlich

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  1. C.L. Dias
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  2. R.C. Rossi
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  3. E.M. Donato
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  4. A.M. Bergold
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  5. P.E. Fröehlich
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Correspondence to P.E. Fröehlich.

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Dias, C., Rossi, R., Donato, E. et al. LC Determination of Ritonavir, a HIV Protease Inhibitor, in Soft Gelatin Capsules. Chroma 62, 589–593 (2005). https://doi.org/10.1365/s10337-005-0670-0

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