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RPL Peptide

Official Technical Documentation

Analytical Methods


Analytical Methods — Tirzepatide

Method Overview

Method Purpose Specification
HPLC Purity Analysis ≥99.0%
LC-MS Identity Confirmation ±0.5 Da
Karl Fischer Water Content <5.0%
LAL Test Endotoxin <5 EU/mg
UPLC Chromatographic Profiling Complimentary
Visual Inspection Appearance White to off-white powder

1. High-Performance Liquid Chromatography (HPLC)

Purpose

Determination of peptide purity by reversed-phase HPLC with UV detection at 214 nm.

Method Parameters

Parameter Specification
Instrument HPLC system with UV/Vis detector
Column C18, 4.6 × 250 mm, 5 μm particle size
Detection UV at 214 nm
Mobile Phase A 0.1% TFA in Water (v/v)
Mobile Phase B 0.1% TFA in Acetonitrile (v/v)
Gradient Program
0–5 min 20% B (isocratic)
5–30 min 20–60% B (linear gradient)
30–35 min 60–80% B (wash)
35–40 min 80–20% B (re-equilibration)
Flow Rate 1.0 mL/min
Injection Volume 20 μL (1 mg/mL solution)
Column Temperature 25°C
Run Time 40 minutes

System Suitability

Parameter Acceptance Criteria
Theoretical Plates ≥10,000
Tailing Factor 0.8–1.5
Resolution ≥2.0 (between main peak and closest impurity)
% RSD (Retention Time) ≤1.0% (6 injections)
% RSD (Peak Area) ≤2.0% (6 injections)

Calculation

Purity (%) = (Main Peak Area / Total Peak Area) × 100


2. Liquid Chromatography-Mass Spectrometry (LC-MS)

Purpose

Confirmation of peptide identity through molecular weight determination.

Method Parameters

Parameter Specification
Instrument LC-MS system with ESI source
Ionization Mode Electrospray Ionization (ESI), Positive
Mass Analyzer Quadrupole or Q-TOF
Scan Range m/z 500–2500
Resolution ≥20,000 (FWHM)
Mass Accuracy ±0.5 Da
LC Conditions Same as HPLC method above

Acceptance Criteria

  • Observed mass within ±0.5 Da of theoretical monoisotopic mass
  • Charge state envelope consistent with peptide molecular weight
  • Deconvoluted mass matches calculated molecular weight

3. Karl Fischer (KF) Moisture Analysis

Purpose

Determination of residual water content in lyophilized peptide.

Method Parameters

Parameter Specification
Method Coulometric Karl Fischer Titration
Sample Size 5–10 mg
Reagent Hydranal-Coulomat AG
Acceptance Criteria <5.0% water content

4. LAL Endotoxin Testing

Purpose

Quantitative determination of bacterial endotoxin levels.

Method Parameters

Parameter Specification
Method Limulus Amebocyte Lysate (LAL) — Kinetic Turbidimetric
Standard Control Standard Endotoxin (CSE)
Acceptance Criteria <5 EU/mg

5. UPLC Chromatographic Profiling

Purpose

Complementary high-resolution chromatographic analysis.

Method Parameters

Parameter Specification
Column C18, 2.1 × 100 mm, 1.7 μm
Detection UV at 214 nm and 280 nm
Flow Rate 0.3 mL/min
Run Time 15 minutes

6. Visual Inspection

Purpose

Qualitative assessment of physical appearance.

Acceptance Criteria

  • White to off-white lyophilized powder
  • Free from visible contamination
  • Intact cake structure

Document Control

Version Date Author Changes
1.0 July 2026 RPL Peptide Quality Initial release

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Official Technical Documentation

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