Simple rapid method for quantification of antiretrovirals by liquid chromatography—tandem mass-spectrometry

Volosov, Andrew; Alexander, Christopher; Ting, Lillian; Soldin, Steven J.

doi:10.1016/s0009-9120(02)00286-2

Cited by 74 publications

(54 citation statements)

References 19 publications

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“…The plasma samples were incubated for 30 min at 56°C to deactivate the HIV particles. Heating of the samples has been proven not to produce degradation of LPV (12,26).…”

Section: Methodsmentioning

confidence: 99%

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Population Pharmacokinetics of Lopinavir Predict Suboptimal Therapeutic Concentrations in Treatment-Experienced Human Immunodeficiency Virus-Infected Children

Rakhmanina¹,

Anker

Baghdassarian³

et al. 2009

Antimicrob Agents Chemother

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In adult protease inhibitor (PI)-experienced patients, a lopinavir (LPV) phenotypic inhibitory quotient (PIQ) of >15 has been associated with a higher likelihood of viral suppression. The aims of this study were to develop a population pharmacokinetic (PK) model of LPV in children and to estimate the probability of achieving a PIQ of >15. HIV-infected, PI-experienced children receiving LPV were intensively sampled for 12 h to measure plasma LPV. The data were fitted to candidate PK models (using MM-USCPACK software), and the final model was used to simulate 1,000 children to determine the probability of achieving an LPV PIQ of >15. In 50 patients (4 to 18 years old), the median LPV plasma 12-hour-postdose concentration was 5.9 mg/liter (range, 0.03 to 16.2 mg/liter) lower than that reported in adults. After a delay, LPV was absorbed linearly into a central compartment whose size was dependent on the weight and age of the patient. Elimination was dependent on weight. The regression line of observed versus predicted LPV had an R 2 of 0.99 and a slope of 1.0. Visual predictive checks against all available measured concentrations showed good predictive ability of the model. The probability of achieving an LPV PIQ of >15 was >90% for wild-type virus but <10% for even moderately resistant virus. The currently recommended dose of LPV/ritonavir appears to be adequate for children infected with wild-type virus but is unlikely to provide adequate inhibitory concentrations for even moderately resistant human immunodeficiency virus (HIV). PI-experienced HIV-infected children will likely benefit from longitudinal, repeated LPV measurement in plasma to ensure that drug exposure is most often near the maximal end of the observed safe range.Lopinavir/ritonavir (LPV/RTV) (Kaletra) is the first and only coformulated RTV-boosted protease inhibitor (PI) approved for use in children. The recommended doses for children who weigh more than 15 kg are 10 mg/kg of body weight or 230 mg/m 2 (body surface area) twice daily, with a maximum of 400 mg per dose unless it is combined with drugs affecting cytochrome (CYP) P450 metabolism, which require LPV dose adjustment (4, 28). Introduced as a salvage agent (22), LPV/RTV has become one of the preferred PI choices for first-line regimens in children Ͼ6 months of age in the countries with access to the drug.Despite evidence for good antiviral efficacy among children in a clinical trial setting (16,17,23), the standard dose may not be adequate for every child. Noncompartmental analysis has shown that the average LPV plasma 12-hour-postdose concentration (C trough ) in children given the currently recommended pediatric dose of LPV is 67% lower than in adults (24). Recently, Jullien et al. published a population pharmacokinetics (PK) model of LPV in children aged 0 to 18 years (15). The model was based on a retrospective analysis of LPV plasma measurements in 157 children, with a median of 3 samples (range, 1 to 14) per patient, obtained for monitoring purposes after self-reported LPV intake. In t...

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“…The plasma samples were incubated for 30 min at 56°C to deactivate the HIV particles. Heating of the samples has been proven not to produce degradation of LPV (12,26).…”

Section: Methodsmentioning

confidence: 99%

“…The LPV plasma concentrations were determined by a tandem-mass spectrometric method using the Applied Biosystems/Sciex API-2000 (12,26). Withinrun error was below 7%, and between-day error was below 10% for all analytes at the tested concentrations.…”

Section: Methodsmentioning

confidence: 99%

Population Pharmacokinetics of Lopinavir Predict Suboptimal Therapeutic Concentrations in Treatment-Experienced Human Immunodeficiency Virus-Infected Children

Rakhmanina¹,

Anker

Baghdassarian³

et al. 2009

Antimicrob Agents Chemother

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“…Several analytical methods have been published for the analysis of EFV in plasma, either alone or in combination with other drugs, using HPLC-UV [14][15][16][17] and LC-MS/MS [18][19][20][21][22][23] techniques. Determination of EFV levels in human hair [7] and reports of determining nevirapine [8,10] and indinavir [24] from saliva have been published, but this study is the first validated LC-MS/MS method for the assay of EFV in saliva to be reported.…”

Section: Discussionmentioning

confidence: 99%

Determination of salivary efavirenz by liquid chromatography coupled with tandem mass spectrometry

Theron

Cromarty

Rheeders

et al. 2010

Journal of Chromatography B

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a b s t r a c tA novel and robust screening method for the determination of the non-nucleoside reverse transcriptase inhibitor, efavirenz (EFV), in human saliva has been developed and validated based on high performance liquid chromatography tandem mass spectrometry (LC-MS/MS). Sample preparation of the saliva involved solid-phase extraction (SPE) on C18 cartridges. The analytes were separated by high performance liquid chromatography (Phenomenex Kinetex C18, 150 mm × 3 mm internal diameter, 2.6 m particle size) and detected with tandem mass spectrometry in electrospray positive ionization mode with multiple reaction monitoring. Gradient elution with increasing methanol (MeOH) concentration was used to elute the analytes, at a flow-rate of 0.4 mL/min. The total run time was 8.4 min and the retention times for the internal standard (reserpine) was 5.4 min and for EFV was 6.5 min. The calibration curves showed linearity (r 2 , 0.989-0.992) over the concentration range of 3.125-100 g/L. Mean intra-and inter-assay relative standard deviation, accuracy, mean extraction recovery, limit of detection (LOD) and limit of quantification (LOQ) were 0.46-9.43%, 80-120%, 60% (±7.95), 1.84 and 6.11 g/L respectively. The working range was defined as 6.25-100 g/L. This novel LC-MS/MS assay is suitable for reliable detection of low EFV concentrations in saliva and can be used as a screening tool for monitoring EFV compliance.

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“…This is because of its long half-life, which means effective concentrations are maintained for long periods. 3 Several methods are described in literature for the quantification of efavirenz in biological fluids by high performance liquid chromatography with ultraviolet detection (HPLC-UV), [4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20][21][22] HPLC with fluorescence detector, 23 liquid chromatography with mass spectrometry detection (LC-MS), 24 liquid chromatography with mass spectrometry in tandem detection(LC-MS/MS) [25][26][27][28][29] and matrix assisted laser desorption/ionization with time-of-flight in tandem detection (MALDI-TOF/ TOF). 30 When sample throughput is an important issue, such as in pharmacokinetic applications, the development of rugged methods with short analysis times becomes an important consideration.…”

Section: Introductionmentioning

confidence: 99%

A sensitive and robust lc-ms/ms method with monolithic column and electrospray ionization for the quantitation of efavirenz in human plasma: application to a bioequivalence study

Bedor¹,

Filho²,

Ramos³

et al. 2011

Quím. Nova

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Recebido em 12/7/10; aceito em 17/12/10; publicado na web em 25/3/11An LC-MS/MS method has been developed for the determination of efavirenz (EFZ) in human plasma using hydrochlorothiazide as internal standard (I.S.). An ESI negative mode with multiple reaction-monitoring was used monitoring the transitions m/z 313.88→69.24 (EFZ) and 296.02→204.76 (I.S.). Samples were extracted using liquid-liquid extraction. The total run time was 2.0 min. The separation was achieved with HPLC-RP using a monolithic column. The assay was linear in the concentration range of 100 -5000 ng mL -1 . The mean recovery was 83%. Intra-and inter-day precision were < 9.5% and < 8.9%, respectively and accuracy was in the range ± 8.33%. The method was successfully applied to a bioequivalence study.

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Simple rapid method for quantification of antiretrovirals by liquid chromatography—tandem mass-spectrometry

Cited by 74 publications

References 19 publications

Population Pharmacokinetics of Lopinavir Predict Suboptimal Therapeutic Concentrations in Treatment-Experienced Human Immunodeficiency Virus-Infected Children

Population Pharmacokinetics of Lopinavir Predict Suboptimal Therapeutic Concentrations in Treatment-Experienced Human Immunodeficiency Virus-Infected Children

Determination of salivary efavirenz by liquid chromatography coupled with tandem mass spectrometry

A sensitive and robust lc-ms/ms method with monolithic column and electrospray ionization for the quantitation of efavirenz in human plasma: application to a bioequivalence study

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